Communication... Surgeon n Perfusion Team

It should be apparent from the preceding sections that any medical procedure as invasive, life-sustaining, and complex in execution as CPB depends on close coordination of activities by all team members. Essential and effective communication provides a means to facilitate such coordination. Instructions or announcements from the surgeon to the perfusionist or anesthesia personnel are necessary during conduct of the operation because CPB is being used to facilitate a surgical procedure. Instructions from the anesthesiologist to the perfusionist also often occur during the period of CPB. All instructions or announcements should be followed by an acknowledgment from the person to whom it was directed. In this manner, errors of omission will be minimized and the surgical procedure can proceed expediently. If acknowledgment does not occur, the communication should be repeated until a response is heard, most often by the intended recipient repeating the instruction to avoid possible errors in interpretation.

The perfusionist should communicate to the surgeon activities that are performed according to protocol or according to surgeon preference. Likewise, the anesthesiologist should communicate activities to the perfusionist that also can affect the conduct of CPB and vice versa. An example would be administration of a vasodilator that can alter the circulating volume of blood and CPB reservoir level. Fluid additions to the CPB circuit should be communicated from the perfusionist to the anesthesiologist because of implications for fluid management after CPB.

Both perfusionist and anesthesiologist are obligated to communicate to the surgeon any significant abnormal conditions they observe. Much of the surgeon's attention may be focused on the surgical procedure, and the perfusionist and anesthesiologist are better able to monitor the key parameters outlined earlier.

Some conditions can occur unexpectedly that may potentially jeopardize patient well-being, including: increased CPB arterial line pressure; sustained decreased venous drainage; nonfunctioning vent or sucker; sustained elevated or low patient arterial blood pressure; elevated CVP, LA, or PA pressures; elevated delivery pressure and/or lower than expected flow during cardioplegia administration; and any potentially life-threatening equipment malfunction or failure. In such instances, immediate communication is required.

Often abnormal situations can occur that are less acute but potentially damaging, including: elevated serum potassium; lower than expected hemoglobin or hematocrit (with or without the expected need for blood transfusion that should be ordered by a physician); higher than expected fluid volume requirements; higher than expected use of vasopressors or need for increased systemic blood flow for decreased systemic vascular resistance; lower than expected mixed S_vO₂; resumption of cardiac electrical or mechanical activity during cardioplegic arrest; and air entrainment in the venous line.

If deep hypothermia and low flow or elective circulatory arrest are required, the surgeon should be notified of the duration of cooling, patient temperature(s), and elapsed times of low flow or circulatory arrest. The frequency for such notification should be communicated to the perfusionist before the procedure or at the time of initiation of low flow or circulatory arrest.

Surgical manipulations of the heart or major vessels may affect CPB. For example, retraction of the heart for surgical exposure may restrict venous drainage or allow air to enter the venous line at the venous cannulation site(s) or through side holes in the cannula exposed to atmosphere if the cannula becomes displaced. Such retraction also may distort the aortic valve, causing aortic incompetence with possible left ventricular distention from flow exiting the arterial cannula. Retraction of the heart may increase or decrease vent return. These conditions should be communicated to the surgeon when they occur, and surgeons should alert the perfusionist when they are displacing the unarrested heart such as when a circumflex coronary artery graft anastamoses is checked for bleeding. Collateral blood flow may partially obstruct the surgical field, necessitating a decrease in CPB systemic flow. Application of the aortic cross-clamp usually is preceded by instruction from the surgeon to the perfusionist to momentarily decrease the systemic blood flow to lower pressure in the aorta. The perfusionist should communicate all changes in systemic blood flow, whether in response to direct instruction or by protocol.

MANAGEMENT OF THE POSTOPERATIVE CARDIAC SURGERY PATIENT

MANAGEMENT OF THE POSTOPERATIVE CARDIAC SURGERY PATIENT

General Principles

If anything unusual happened.. ask the surgeon and assist him

• Admission notes: preop – comorbidities cardiac investigations

medications intraop – operation notes and anaesthetic record

particular problems – weaning off bypass,

ventricular function, bleeding • Examination – vitals, circulation, drains, pacemaker wires

• Routine bloods – CBP, Clotting, LFT, RFT, ACT, ABG • CXR, ECG • Follow target filling pressures by surgeons • Medications: Cefuroxime 750mg Q8H for 3 doses (unless allergy)

Bactroban topical nasal tds Continue inotropes and/or vasodilators from OT and wean as appropriate. If increasing inotropic support is required – inform ICU senior and surgeon

Important ***: • Keep patients on GTN infusion for patients with LIMA graft (to reduce

vasospasm risk) •

. You may have to end up using an anti-hypertensive to maintain BP within agreed parameters and fluids to maintain CVP

• Intravenous fluids: 5% dextrose with KCl 20mmol in 500 ml solution at 1ml/kg/hr. If K+ level > 5.5 mmol/l omit KCl supplement

• ABG on admission: if K+ level between 4.5-5.5 mmol/l repeat ABG Q2H for 24 hours. If K+ level < 4.5 or > 5.5mmol/l, repeat ABG until corrected.

• Glucose control: follow glucose nomogram • If urine output < 1ml/kg/hr, consider frusemide especially in patients

receiving it preoperatively and if CVP/PCWP > 14mmHg with

good peripheral perfusion • Pacemaker at the bedside of all cardiac patients while in ICU

Identify if pacing wires present If pacemaker from OT attached and operational, continue with appropriate pacing. If no pacemaker from OT or patient is NOT being paced by OT pacemaker, replace OT pacemaker with ICU pacemaker

Respiratory Management

• Following surgery commence all patients on an ICU ventilator • After the first ABG, adjust the FiO2 to maintain a PaO2 >10kPa • Wean from ventilation according to past medical history, surgery

performed and current clinical status • Extubation criteria:

Temperature > 360C Awake, analgesed, able to protect airway with a good cough Cardiovascularly stable - MAP >60mmHg, pH 7.35-7.45 Adequate gaseous exchange – PaO2 >10kPa on FiO2 0.4 Minimal bleeding – drain output <100ml/hour

• Respiratory failure post-op secondary to collapse/consolidation is common. Ensure good analgesia and frequent, effective physiotherapy.

Management of Bleeding

• *** Call cardiac surgeon early whilst you are continuing with your management

• Perform appropriate investigations: ACT, INR, APTT, platelet count • Treat abnormalities of above:

Protamine 50mg if ACT >150 s FFP if INR abnormal If no response then platelet transfusion of 5 units, irrespective of platelet count

• If on aprotinin, continue at 50ml/hr (500,000 units) until bleeding <50ml/hr from pericardial drain

• If bleeding continues or is brisk, perform CXR (look for enlarging heart shadow) and echocardiogram* to exclude tamponade and obtain early review by cardiothoracic surgeons.

• * echocardiogram can be performed by some of our ICU doctors. Otherwise get on-call cardiologist. Check with chief cardiac surgeon first before you consult cardiologist.

• Ensure that bedside sternotomy set ready at all times • Consider re-opening if:

bleeding >200ml/hr for 3-4 hours bleeding >400ml/hr in 1 hour total loss >1500-2000mls

Hypotension (SBP <100mmHg or MAP <60mmHg)

Gradual decline in BP

• Correct fluid/blood losses as appropriate using blood or colloid • Early ECG, Echo and inform cardiothoracic surgeons • Treat reversible causes – bleeding, pneumothorax, tamponade, kinked

graft, graft vasospasm • Treat arrhythmia • Inotropes

Dopamine/dolbutamine – mild hypotension Adrenaline Noradrenaline – severe resistant hypotension with low SVR IABP

Sudden and severe hypotension • Call chief cardiac surgeon and senior ICU staff immediately. Inform

theatre • While routine resuscitation underway – exclude tension pneumothorax,

echocardiography, consider opening chest in ICU

Hypertension

• The MAP is to be kept quite strictly at about 60-80mmHg for the first 24- 36hours

• This may vary according to the patient’s preoperative blood pressure and condition (e.g. carotid stenosis). Must discuss with cardiothoracic team if the targets need to be adjusted

• Ensure adequate analgesia: give morphine if patient is in pain • Titrate GTN infusion or Nitroprusside infusion to maintain MAP of 60-

80mmHg • If hypertension persists – (please discuss with ICU senior and surgeon

first) β blocker: atenolol 1-2mg IV or esmolol 10-25mg IV (if no contraindication and good LV). Must be used cautiously after valve surgery.

Arrhythmias

• Treat electrolyte abnormalities, hypoxia, hypercarbia, tamponade, hypotension

• Bradycardia – AV sequential pacing first if < 60 beats per minute • Atrial fibrillation – if K+< 4 give potassium, if K+ >4.5 give amiodarone,

cardioversion (inform ICU senior and surgeon first) • VPB – lignocaine – check K+ and Mg++ • Pulseless VT or VF – defibrillate (observe protocol for defibrillation, inform

ICU senior and surgeon) • Note

o Defibrillation for monophasic defibrillators: 200J, 300J, 360J o Defibrillation for biphasic defibrillators: 150J non-escalating

Anticoagulation

• Patients with saphenous vein grafts should receive aspirin 160mg oral after 24 hours if not bleeding

• Commence patients with valve replacements on warfarin from the second post-operative day if extubated (we very rarely have to prescribe as majority of patients discharged by then. Dosing, best check with surgeon first)

• Patients with a valve replacement ventilated >48hours may require heparinisation

ST Segment Elevation (new! Pending approval from ICU director and chief cardiac surgeon)

• All cardiac patients should have continuously ST segment monitoring • Note pattern of ST elevation (site, up slopping etc) • Check patient’s clinical status (e.g. check vitals, ask for chest pain, check

if patient cold and sweaty, check peripheral circulation and auscultate for

pericardial rub) • Check preoperative ECG and compare • Inform cardiac surgeon • For patients with arterial grafts, continue GTN infusion.

Consider diltiazem if suspect graft vasospasm (discuss with ICU senior and

cardiothoracic surgeons first)

If a cardiac patient deteriorates acutely for whatever reason: • Call cardiac surgeon (as well as chief) and ICU senior stat • Immediate availability of sternotomy set, gowns, gloves, towels,

betadine • Immediate availability of resuscitation trolley •

Inform OT control and request OT nurse for assisting surgeon

Cardiology's 10 Greatest Discoveries of the 20th Century

Cardiology's 10 Greatest Discoveries of the 20th Century

.... but still.. nothing compare to Coronary Surgery..

Nirav J. Mehta, MD and Ijaz A. Khan, MD, FACC

Division of Cardiology, Creighton University School of Medicine, Omaha, Nebraska 68131

Abstract

We present a brief summary of the 10 greatest cardiologic developments and discoveries of the 20th century. Described are electrocardiography; preventive cardiology and the Framingham Study; “lipid hypotheses” and atherosclerosis; coronary care units; echocardiography; thrombolytic therapy; cardiac catheterization and coronary angiography; open-heart surgery; automatic implantable cardiac defibrillators; and coronary angioplasty. These topics are the personal choices of the authors. (Tex Heart Inst J 2002;29:164–71)

Key words: Angioplasty, balloon; angioplasty, transluminal, percutaneous coronary; atherosclerosis; cardiology; cardiovascular diseases/epidemiology; coronary angiography; coronary artery bypass grafting; coronary care units; echocardiography; electrocardiography; equipment design; heart catheterization; heart-lung machine; history of medicine, 20th cent.; hypercholesterolemia/prevention & control; myocardial infarction/therapy; open-heart surgery; pacemaker; risk factors; thrombolytic therapy

The great success in lowering cardiovascular mortality rates during the last decades of the 20th century are secondary to the extraordinary strides made in the understanding of basic cardiovascular science and in the development of new diagnostic and therapeutic techniques. We describe the 10 most important cardiologic developments and discoveries of the last century. Without these, the cardiology that we practice today would not be possible. The 10 topics were selected on the basis of personal choice.

1. Electrocardiography

During the latter part of 19th century, much research centered around the electrical activity of the heart, although some of the 1st investigators were unaware of the clinical usefulness of recording cardiac electrical activity. As late as 1911, Augustus Waller, who was the pioneer of electrocardiography, said, “I do not imagine that electrocardiography is likely to find any very extensive use in the hospital. It can at most be of rare and occasional use to afford a record of some rare anomaly of cardiac action.” ¹ However, just 13 years later, the Nobel Prize in Medicine was awarded to Willem Einthoven, who transformed this curious physiologic phenomenon into an indispensable clinical recording device.

Rudolf von Koelliker and Heinrich Müller were the first to discover, in 1856, that the heart generated electricity. ² The 1st successful recording of electrical rhythm in the human heart seems to have been made by Alexander Muirhead in 1869–70, using a Thomson siphon recorder at St. Bartholomew's Hospital, London. This equipment was originally devised to record signals passing through the transatlantic cable, which had been laid in 1866. ³ Waller performed his work in the development of electrocardiography at St. Mary's Hospital, Paddington, London. He used the Lipmann capillary electrometer to record electrical reactions of the human heart. In 1887, Waller published the 1st report of a recording of cardiac electricity on the body's surface; he called the recording a “cardiograph.” ⁴ Waller presented his paper titled “A preliminary survey of 2,000 electrocardiograms” before the Physiological Society of London in 1917. ⁵ Among his contributions were the variability of the electrogram, the dipole concept that led to isopotential mapping, and the vector concept.

Einthoven, born in 1860 in Java, Dutch East Indies (now Indonesia), attended the University of Ütrecht Medical School. ² In 1887, Einthoven was present at the International Congress of Physiology in London, where he observed Waller demonstrating the use of the capillary electrometer to record an “electrograph” of the heart. ⁶ Einthoven began to explore the use of the capillary electrometer to record minute electrical currents. In 1895, he was able to detect recognizable waves, which he labeled “P, Q, R, S, and T.” The limitations of capillary electrometers led Einthoven to devise a string galvanometer to record cardiac electrical activity. ^2,3,6,7 With his new technique, he standardized the tracings and formulated the concept of “Einthoven's triangle” by mathematically relating the 3 leads (Lead III = Lead II – Lead I). He described bigeminy, complete heart block, “P mitrale,” right and left and ventricular hypertrophy, atrial fibrillation and flutter, the U wave, and examples of various heart diseases. ^2,6,7 Johannes Bosscha, one of Einthoven's teachers, suggested using existing telephone lines to link the hospital to Einthoven's physiology laboratory. This idea increased the clinical availability of Einthoven's instrument by enabling electrocardiographic studies to be made in hospitalized patients. ⁸

Within 10 years of Einthoven's clinical studies with the string galvanometer, the potential of electrocardiography was realized. Many arrhythmias were recognized, and the associations of T-wave inversion with angina and arteriosclerosis were identified in 1910. The “father of electrocardiography” was honored with the Nobel Prize in Medicine in 1924. His important contributions laid the foundation for the great discoveries of the 20th century and further advances in the field of cardiology.

2. Preventive Cardiology and the Framingham Study

The Framingham Study is one of the most impressive medical works in the 20th century. ⁹ During the 1st half of the century, there was a steady increase in deaths attributed to heart disease. However, the causes of coronary heart disease were speculative. Investigations comprised descriptive case reports and case-control comparisons of small studies only. ¹⁰ With support from the newly created National Heart Institute (now National Heart, Lung, and Blood Institute [NHLBI]), the 1st collection of information from a community cohort was gathered. Between 1948 and 1951, 1,980 men and 2,421 women were enrolled in an observational study in Framingham, Massachusetts. The 1st report of this long-term study, “Factors of risk in the development of coronary heart disease—six-year follow-up experience; the Framingham Study,” was published in the Annals of Internal Medicine in 1961. ¹¹ The study showed that high blood pressure, smoking, and high cholesterol levels were major factors in heart disease. From this report, the concept of risk factors emerged, and, with further elaboration through the years, the study provided health professionals with multifactorial risk profiles for cardiovascular disease. These profiles assisted in the identification of candidates who might benefit from preventive measures. The Framingham Study provided information crucial to the recognition and management of atherosclerosis, its causes, and its complications. Fifty years' worth of data collected from the residents of Framingham has produced over 1,000 scientific papers; introduced the concepts of biologic, environmental, and behavioral risk factors; identified major risk factors associated with heart disease, stroke, and other diseases; created a revolution in preventive medicine; and forever changed the ways in which the medical community and the general population view the genesis of disease. Of note, the Framingham Study was the 1st major cardiovascular study that included women participants. Not only was the Framingham Study a milestone in the history of cardiology, but it has served as the model for many other longitudinal cohort studies. We remain indebted to those who initiated the study and thus became pioneers in preventive cardiology.

3. “Lipid Hypotheses” and Atherosclerosis

During the 19th century, arteriosclerosis was well recognized, but its etiologic and pathologic significance had not been established. The hypotheses explaining it ranged from disturbed arterial metabolism to adherent blood clots that gradually changed into arteriosclerotic plaques. In 1904, Felix Marchand introduced the term atherosclerosis and suggested that atherosclerosis was responsible for nearly all obstructive processes in the arteries. ¹²

In St. Petersburg, Russia, in 1908, A.I. Ignatowski observed a possible relation between cholesterol-rich foods and experimental atherosclerosis. ¹³ Another sign that cholesterol might be involved in the pathogenesis of atherosclerosis came 2 years later, when Adolf Windaus showed that atheromatous lesions contained 6 times as much free cholesterol as a normal arterial wall and 20 times more esterified cholesterol. ¹⁴ Using cholesterol-fed rabbits to produce experimental atherosclerosis, Nikolai Anichkov demonstrated, in 1913, that it was cholesterol alone that caused these atherosclerotic changes in the rabbit initima. ¹⁵ He found early lesions, such as fatty streaks, as well as advanced lesions; by standardizing cholesterol feeding, he discovered that the amount of cholesterol uptake was directly proportional to the degree of atherosclerosis severity. William Dock, in an editorial in 1958, likened the significance of this classic work by Anichkov to that of the discovery of the tubercle bacillus by Robert Koch. ¹⁶

During the 1930s, studies of the blood concentration of cholesterol began, but most of the medical community did not comprehend the clinical importance of such studies. In 1950, John Gofman and his associates identified the low-density lipoprotein (LDL) cholesterol and high-density lipoprotein (HDL) cholesterol using the ultracentrifuge technique. ¹⁷ In addition, they found that 101 of 104 men with myocardial infarction had elevated LDL molecules—a finding which they had also observed in their cholesterol-fed atherosclerotic rabbits. Gofman's group observed an inverse relationship between HDLs and risk of coronary artery disease. In 1952, Laurence Kinsell and coworkers found that ingestion of plant foods and avoidance of animal fats decreased the blood level of cholesterol. ¹⁸ The most important study to identify blood cholesterol level as a risk factor for coronary artery disease was the Framingham Study, which showed that the risk of developing clinically significant coronary artery disease was a continuous curvilinear function of blood cholesterol levels.

During the 1950s and 1960s, many cholesterol-lowering agents were introduced into clinical use, including nicotinic acid, cholestyramine, clofibrate, and plant sterols. In 1961, the American Heart Association began encouraging people to follow a “prudent diet;” ¹⁹ and in 1964, Konrad Bloch and Feodor Lynen received the Nobel Prize in Medicine for their work on the metabolism of cholesterol and fatty acids. During the 1970s, Michael Brown and Joseph Goldstein found the LDL receptor and the LDL pathway and shared the 1985 Nobel Prize in Medicine. Another major breakthrough in the pharmacologic management of hypercholesterolemia was the discovery of the statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors). Akira Endo in Japan discovered the earliest statin, compactin, in 1976. ²⁰ In 1985, the NHLBI established the National Cholesterol Education Program to educate both physicians and patients about the importance of treating hypercholesterolemia, and the 1st guidelines were published in 1988. ²¹ The more that the beneficial effects of lipid-lowering interventions became manifest via large clinical and angiographic trials, the more such interventions were used in clinical practices for the primary and secondary prevention of coronary artery disease.

4. Coronary Care Units

In the early 1960s, the technique of closed-chest cardiopulmonary resuscitation and continuous telemetry monitoring with an alarm system laid the groundwork for coronary care units (CCUs)—specialized intensive care units for patients with acute myocardial infarctions (AMIs). These developments were combined with 2 simple strategies: 1) the clustering of patients with AMIs on a single hospital unit, where necessary equipment and drugs were readily available and where trained personnel could be in continuous attendance; and 2) the training of specialized nurses to recognize and treat arrhythmias rapidly in the absence of a physician. ²² The major objective was to reduce the number of deaths caused by arrhythmias. However, no measures were available to manage overwhelming shock or refractory pulmonary edema resulting from pump failure. Desmond Julian presented the 1st description of the CCU to the British Thoracic Society in July 1961. ²³ The next year, Gaston Bauer and Malcolm White started a CCU in a Sydney hospital. Around the same time, K.W.G. Brown in Toronto, Hughes Day in Kansas, and Lawrence Meltzer in Philadelphia began monitoring patients with myocardial infarctions in CCUs. ²³ The importance of the specialized care administered in the CCU was realized in 1967 when Thomas Killip and John Kimball published their experience consisting of 250 patients with AMIs who had been treated in the CCU. Compared with other patients who had experienced AMIs, those treated in the CCU had better survival rates in the absence of cardiogenic shock. ²⁴ Other centers reported similar results. ^25–27

From experience gained in the early CCUs, it soon became apparent that arrhythmias were much more common than had previously been suspected. Ventricular extrasystoles were found to be almost universal and generated a lot of interest as “warning” arrhythmias. Bernard Lown and colleagues reported that they found no occurrence of ventricular fibrillation when patients who experienced warning arrhythmias were treated with lidocaine. ²⁷ The development of CCUs coincided with a rapid expansion in the use of transvenous pacing, which was performed in 35% of patients with AMIs at the New York Hospital–Cornell Medical Center in 1967. ²⁵

Early success in CCUs with resuscitation and with the detection and treatment of arrhythmias focused researchers' attention on left ventricular failure and cardiogenic shock. The Myocardial Infarction Research Units were created in the United States by the NHLBI, and a large program of research was initiated for the investigation of the hemodynamic effects of myocardial infarction. The Swan-Ganz flow-guided catheter was introduced, and its use for invasive monitoring of cardiac hemodynamics became routine in some centers. ²³

5. Echocardiography

The evolution of ultrasonography dates back to 1880, when Pierre and Jacques Curie discovered piezoelectricity. ²⁸ During World War II, the field of sonar ultrasonography advanced rapidly because of its use for detecting submarines. The pioneers of echocardiography were Inge Edler, a cardiologist at Lund University in Sweden, and Hellmuth Hertz, a Swedish physicist. ²⁹ Edler and Hertz borrowed a sonar device from a local shipyard, improved it, and recorded cardiac echoes from Hertz's own heart. With the development of this ultrasonic “reflectoscope,” the new field of echocardiography emerged. Edler and Hertz first reported the continuous recording of movements of the heart walls in 1954 and described the use of the ultrasonic cardiogram for mitral valve diseases in 1956. ³⁰ Edler identified several structures on the echocardiogram and made a film that was shown at the European Congress of Cardiology in 1960. With the development of Doppler echocardiography in the 1960s, the ink-jet printer (another invention by Hertz) was useful in the development of the color Doppler technique. In 1977, Edler and Hertz were joint recipients of the Lasker Prize, which is the American equivalent of the Nobel Prize in Medicine.

In Germany, Sven Effert and his colleagues identified left atrial masses using cardiac ultrasound in 1959. ³¹ Effert's team visited the United States in the early 1960s, where they met Claude Joyner and discussed the potential of ultrasonography, including the advantages of its nonhazardous nature. At the University of Minnesota, John Reid, an electrical engineer, with John Wild, worked on tissue characterization using ultrasound and developed the 1st clinical ultrasonic scanner. Later, Reid became a member of Joyner's group in Philadelphia where, in 1963, they published the 1st American article on echocardiography. ³² The American achievements in early clinical echocardiography are credited to Harvey Feigenbaum, who led research in the new field of cardiac ultrasonography. In 1968, in Indianapolis, he started the 1st academic course dedicated solely to cardiac ultrasonography, and in 1972, he wrote the 1st book on echocardiography. ³³ As this subspecialty gained acceptance and applicability, newer techniques—such as 2-dimensional, transesophageal, and Doppler echocardiography—were introduced.

6. Thrombolytic Therapy

One of the last century's most exciting developments in the field of cardiology was the introduction of thrombolytic therapy for use in patients experiencing AMIs. In 1933, William Tillet and R.L. Garner discovered that Group A β-hemolytic streptococci produced a fibrinolytic substance, which they called streptococcal fibrinolysin. ³⁴ Haskell Milstone, in 1941, suggested that a plasma factor, which he called a “plasma lysing factor,” was necessary for streptococcal-mediated fibrinolysis. ³⁵ L. Royal Christensen, a microbiologist, was able to describe the entire mechanism of streptococcal fibrinolysis in 1945. He showed that human plasma contained the precursor of an enzyme system, which he called plasminogen, and that the streptococcal fibrinolysin, which he named streptokinase, was an activator that could convert plasminogen to the proteolytic and fibrinolytic enzyme plasmin. ^36,37 Two years later, Christensen made available to Tillet a crudely purified preparation of streptokinase. Sol Sherry, Alan Johnson, and George Hazlehurst soon joined Tillet in performing animal experiments with streptokinase in order to determine its efficacy in the treatment of acute coronary thrombosis. ³⁸ In 1952, Tillet and Johnson reported lysis of experimental thrombi in rabbits' ears with intravenous streptokinase administered through a peripheral vein. ³⁹ Five years later, Sherry's group reported a rational approach to thrombolysis using a loading dose and a sustaining infusion of streptokinase sufficient to increase the clot-dissolving activity of plasma by several hundred-fold and to maintain a plasma streptokinase concentration of about 10 μ/mL. ⁴⁰

The 1st study of intravenously administered streptokinase was performed in patients who had AMIs in 1958. ⁴¹ The importance of thrombolysis in such patients was highlighted when Marcus DeWood provided angiographic evidence of a very high incidence of total occlusion of infarct-related arteries during the early period of infarction, ⁴² and Peter Rentrop and his group demonstrated rapid recanalization after local administration of streptokinase directly into an infarct-related artery. ⁴³ Thereafter, the Netherlands trial, the Western Washington trials, and ISIS-2 demonstrated both short- and long-term benefits of thrombolytic therapy. ^44–46

7. Cardiac Catheterization and Coronary Angiography

In 1844, Claude Bernard, a noted French research physiologist, used catheters to record intracardiac pressures in animals and coined the term “cardiac catheterization.” ⁴⁷ With the discovery of x-rays in 1895 by Wilhelm Roentgen, a new approach to the study of cardiac anatomy became possible. ⁴⁸ Two 2 German physicians, Friedrich Jamin and Hermann Merkel, published the 1st roentgenographic atlas of the human coronary arteries in 1907. In this publication, the authors presented their study of 29 hearts in which the coronary arteries were injected with a suspension of red lead in gelatin. ⁴⁹ In 1929, a young surgical resident, Werner Forssmann, performed the 1st documented human cardiac catheterization on himself in Eberswald, Germany. He anesthetized his left elbow, inserted a catheter into his antecubital vein, and confirmed the position of the catheter tip in the right atrium by use of radiography. His goal was to find a safe and effective way to inject drugs for cardiac resuscitation. ⁵⁰ Forssmann soon extended his experiments to include the intracardiac injection of contrast material through a catheter placed in the right atrium. His contributions, along with the development of nontoxic contrast media and the steady advances in radiological techniques, prepared the way for the development of coronary angiography. ⁵¹

André Cournand and Dickinson Richards, in 1941, used the cardiac catheter as a diagnostic tool for the 1st time, applying catheterization techniques to measure right-heart pressures and cardiac output. ⁴⁷ For their landmark work, they shared a Nobel Prize in Medicine with Forssmann in 1956. In 1958, Mason Sones performed selective coronary arteriography in a series of more than 1,000 patients, and he published a brief description of his technique in Modern Concepts of Cardiovascular Diseases 4 years later. ⁵² This development initiated a period of rapid growth in coronary arteriography during the mid 1960s. Melvin Judkins, a radiologist who had studied coronary angiography with Sones, created his own system of coronary imaging in 1967, introducing a series of specialized catheters and perfecting the transfemoral approach. ⁵³

8. Open-Heart Surgery

Wilfred Bigelow and his team performed open-heart procedures in animals with the use of hypothermia in 1949. ⁵⁴ This prompted more research on the applicability of hypothermia in human beings. In 1953, John Lewis performed the 1st successful closure of an atrial septal defect in a 5-year-old girl, using the open-heart hypothermic technique that Bigelow's group had developed. ⁵⁵ In the decade between the mid-fifties and the mid-sixties, surgical research was very much focused on various techniques of hypothermia and their possible clinical application.

The heart-lung machine, which offered additional protection to vital organs, was used by John Gibbon in 1953 during the repair of an atrial septal defect and was a major advance in open-heart surgery. ⁵⁶ In “Milestones in Chest Surgery,” Eloesser wrote, “Gibbon's idea and its elaboration take their place among the boldest and the most successful feats of man's mind.” ⁵⁷ The experience gained with open-heart surgery for congenital lesions enabled surgeons to attempt cardiac valve repair and replacement. In 1956, Walton Lillehei and his team corrected pure mitral regurgitation with suture plication of the commissures under direct vision. After that time, many surgeons around the world became involved in direct vision repair, ⁵⁸ and prosthetic valves were introduced for cardiac valve replacement.

In 1935, Claude Beck of the Cleveland Clinic published his classic paper, “The development of a new blood supply to the heart by operation,” which described his technique of grafting a flap of the pectoralis muscle over the exposed epicardium to create a new blood supply. ⁵⁹ His work in myocardial revascularization spanned more than 3 decades and captured the imagination of many surgeons. Arthur Vineberg used the internal mammary artery to provide a new source of blood to the myocardium in 1946. ⁶⁰ This technique became very popular; about 5,000 such operations were performed between 1950 and 1970. In 1964, Vasilii Kolessov, a Russian cardiac surgeon, performed the 1st internal mammary artery–coronary artery anastomosis. ⁶¹ René Favaloro achieved a physiologic approach in the surgical management of coronary artery disease—the bypass grafting procedure—at the Cleveland Clinic in May of 1967. ⁶² He used a saphenous vein autograft to replace a stenotic segment of the right coronary artery. Later that year, he began to use the saphenous vein as a bypassing channel. Soon Dudley Johnson extended the bypass procedure to include the left coronary arterial systems. ⁶³ In 1968, Charles Bailey and Teruo Hirose ⁶⁴ and George Green ⁶⁵ used the internal mammary artery instead of the saphenous vein for bypass grafting. Today, coronary artery bypass grafting has become one of the most common operations and is performed all over the world.

9. Automatic Implantable Cardiac Defibrillators

Perhaps the 1st successful attempt at electrical defibrillation occurred in 1775 when Peter Abildgaard, a Danish veterinarian, evaluated the effects of electrical shock and countershock on chickens. ⁶⁶ In 1899, Jean-Louis Prevost and Frederic Batelli were the first to thoroughly study the effects of electrical discharge on the heart. They noted that if shock was applied within seconds of the onset of fibrillation, the result was defibrillation, which successfully restored sinus rhythm. ⁶⁷ During the early 1930s, D.R. Hooker and his team refined the existing knowledge about defibrillation. ⁶⁸

The original concept of the artificial pacemaker is attributed to Albert Hyman, whose paper on the topic appeared in the Archives of Internal Medicine in 1932. ⁶⁹ Fifteen years later, Beck was the first to apply electrical defibrillation to a human heart in the operating room. ⁷⁰ Bigelow, John Callaghan, and John Hopps, at the Banting Institute in Toronto, developed a technique of transvenous pacing, which they reported in 1950; Smith and Stone Ltd. built the 1st commercial pacemaker to their design. ⁷¹ In 1956, Paul Zoll and coworkers performed the 1st successful external defibrillation in a human subject. ⁷² In Sweden, Åke Senning and Rune Elmqvist designed a miniature pulse generator, which was implanted after a thoracotomy in 1958. ⁷³ Wilson Greatbatch, in the United States, devised an implantable pacemaker powered by a mercury-zinc battery. ⁷⁴ The early devices were all asynchronous; the 1st atrioventricular (AV) synchronous pacemaker, which simulated a true physiologic state, was implanted in 1962. ⁷⁵

These achievements and the expanding knowledge of clinical electrophysiology led to the invention of the automatic implantable cardiac defibrillator (AICD). This device was meant to abort ventricular fibrillation at its onset, thus averting the inevitably fatal outcome. Michel Mirowski, Morton Mower, and William Staewen at Sinai Hospital of Baltimore collaborated on the AICD in 1969. The next year, they published their animal experiments in the Archives of Internal Medicine. ⁷⁶ The concept of the AICD generated a lot of criticism, ⁷⁷ but the Baltimore group continued to pursue their research. Marlin Heilman (the founder of Medrad, a small company that supplied angiographic catheters), joined that group in 1972. Heilman helped to make sensing circuits that could identify ventricular fibrillation on the basis of a mathematical formula called the probability density function. ⁷⁷ In February 1980, after extensive animal research, Mirowski's team successfully treated their 1st human patient with an AICD. ⁷⁸ In their first 50 patients, the mortality rate was less than 10%. Soon the AICD became the treatment of choice for patients with life-threatening ventricular tachyarrhythmias by consistently outperforming the best medications available for these patients.

10. Coronary Angioplasty

In 1964, Charles Dotter and Melvin Judkins described a new technique for relieving stenosis of the iliofemoral arteries with rigid dilators. ⁷⁹ Despite the fact that this technique was developed in Oregon, the procedure was largely ignored in the United States because of technical difficulties and complications. Nonetheless, this technique was used to treat large numbers of patients in Europe. In Zurich, Andreas Gruentzig substituted a balloon-tipped catheter for the rigid dilator and performed the 1st peripheral balloon angioplasty in a human being in 1974. ⁸⁰ After achieving success with coronary angioplasty in animals, Gruentzig and his colleagues performed the 1st intraoperative balloon angioplasty on the human heart. Soon, Gruentzig accomplished the 1st coronary angioplasty in a patient who was awake. On 16 September 1977, Gruentzig performed balloon angioplasty on an isolated stenosis of the proximal left anterior descending coronary artery in a 37-year-old man who had consented to angioplasty even after being informed that he would be the 1st patient so treated. ⁸¹ This procedure was followed by a landmark article in the New England Journal of Medicine by Gruentzig's team, in which they described their technique of percutaneous transluminal coronary angioplasty (PTCA) as used in 50 patients. ⁸² The Gruentzig technique took the cardiologic community by storm, and the era of interventional cardiology was born. This extraordinary achievement could not have been accomplished without the previous development of coronary angiography, coronary bypass surgery, and peripheral vascular dilatation. An international registry of PTCA was established to provide a method for systematic evaluation of this new procedure. Even after Gruentzig's untimely death in 1985, his technique continued to evolve and subsequently led to applications such as coronary atherectomy (1986) and coronary stenting (1987). By 1997, angioplasty had become one of the most common medical interventions in the world.

Preoperative Evaluation for Cardiac Surgery..Simple Notes

Preoperative Evaluation for Cardiac Surgery

improved risk-adjusted mortality for CABG of less than 2% for the general population

particular attention should be paid to the patient's risk for 
   -endocarditis, 
    -the presence of aortic insufficiency, 
    -the presence of vascular disease, and 
    -the neurologic status.
    -conduit ..vein/arteial.. Ima for mastectomy

    -contraindications to the use of an intra-aortic balloon pump, which include aortic insufficiency, severe peripheral vascular insufficiency, abdominal aortic aneurysm, or significant atherosclerosis

 
Examination of the head, eyes, ears, throat, and teeth for infection is helpful in the assessment of an individual's risk of endocarditis in valvular surgery. Inspection of the patient's skin is helpful in detecting and preventing infection (e.g., the presence of tinea pedis on the lower extremities increases the risk of lower extremity cellulitis). Identifying the presence of an aortic regurgitation murmur is important because regurgitation can worsen during cardiopulmonary bypass and acute left ventricular distention may develop.

Basic laboratory testing prior to cardiac surgery should include 
    -a complete blood count, anemia tdk blh, ec hemodilusi intraop 
    -coagulation screen,   
    -chemistry profile, f hepar/renal u obat anest
    -electrolitr, ... U risk arythmia 
    -stool hematest, 
    -evaluation of ventricular function, and 
    -assessment of coronary anatomy via cardiac catheterization
    -nutrisi, albumin <2.5...dikoreksi skt 1wk, ec risk sepsis/resp failure Myocard consumtion naik .     -chf     -as     -lm disease Kl plu transfusi preop... Individuals with mitral regurgitation and heart failure should receive preoperative afterload reduction with angiotensin-converting enzyme (ACE) inhibitors or intravenous sodium nitroprusside to maintain systolic blood pressures in the 90 to 100 mm Hg range.   While patients with aortic stenosis and hemodynamically significant cerebral or renovascular disease should not receive the latter therapies, intra-aortic balloon counterpulsation (IABP) may be useful in such subgroups. Intra-aortic balloon support can also be used in the setting of acute mitral regurgitation due to papillary muscle rupture as well as in infarct-related ventricular septal defect. Preoperative IABP use in high-risk patients decreases mortality and shortens ICU stay due to enhanced hemodynamic performance Right ventricular dysfunction caused by increased pulmonary vascular resistance should be treated with inotropes that have vasodilator properties such as dobutamine (5 µg/kg/min) and milronone (5 µg/kg/min). Intravenous nitrates, prostacyclin (0.5–2.0 ng/kg/min), and nitric oxide (10–20 ppm) are also effective agents for lowering pulmonary vascular resistance with resultant improvement in right ventricular function (COPD), -prolonged weaning from mechanical ventilation postoperatively is common if FEV1 is less than 65% of VC or if FEV1 is less than 1.5 L. CABG patients with severe COPD are more likely to develop ventilatory failure and have higher mortality rates than those with mild-to-moderate or no COPD (death: 19% vs. 4% vs. 2%, p = .02). -Preoperative screening of arterial oxygen concentration on room air can provide guidance in respiratory management postoperatively.  -preoperative spirometry and perioperative bronchodilators remains unclear in stable patients and cannot be recommended on a routine basis The postoperative hypermetabolic state requires increased nutrition in order to facilitate wound healing and to meet corporal metabolic demands.  -patients who are malnourished preoperatively should receive at least 2 to 4 weeks of intensive nutritional bolstering prior to elective surgery, and all patients should resume an oral diet within 24 hours after uncomplicated surgery. Since perioperative stroke may limit the ability of some patients to protect their airway, a swallowing evaluation is mandatory in this subset of patients.  -Early enteral feeding is warranted in those individuals who have no contraindications to feeding. Low body mass index (<20 kg/m2) and hypoalbuminemia (<2.5 g/dL) are independently associated with increased risk of morbidity and mortality after cardiac surgery. -Patients with decreased albumin levels are at increased risk for bleeding, renal failure, prolonged ventilatory support, and reoperation.  -obesity is not associated with increased mortality, patients with high percent body fat and poor aerobic capacity are at higher risk for sternal wound infection (OR = 2.3; p<.001), saphenous vein harvest site infection, and atrial arrhythmias -Preoperative temporary transvenous pacemaker wire insertion is recommended in patients with hemodynamic instability and high-grade heart block (third degree or Mobitz II).  -Permanent epicardial pacing lead implantation should be done intraoperatively for patients undergoing tricuspid valve replacement with a mechanical prosthesis, due to the contraindication of passing a transvenous lead through the latter. HIt ..white clot syndrm... Immune... Vein arterial pulmonal trombois...Hit igG -penurunan tc >50%, at >30% bl ada gjl pdarahan/trombosis
-pd pts dg heparin (ufh/lmwh), min 5d-14d
-risk ; heparinisasi in 3bln
-if stopped.. Tc naik within days n pdarahan/tromosis within 1bln
Treathment
-delay 3bln
-warfarin initiation should be done in the presence of lepirudin or argatroban due to warfarin's association with limb gangrene

In the PURSUIT trial, patients who received the glycoprotein IIb/IIIa inhibitor eptifibatide within 30 days of CABG did not experience higher rates of bleeding, probably due to the short half-life of the drug. 
However, the CURE trial showed that the antiplatelet agent clopidogrel was beneficial in patients with acute coronary syndromes undergoing PCI but was associated with a concomitant increased risk of major bleeding.34 Though clopidogrel can decrease mortality, it may potentially pose serious problems with major perioperative bleeding (clopidogrel vs. placebo .The median time between discontinuation of clopidogrel and CABG was 5d
Limited data are available regarding the use of fibrinolytic agents prior to CABG. However, in a subgroup analysis of the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries trial (GUSTO I), patients who underwent PCI or CABG after receiving fibrinolytics had a lower rate (0%) of intracranial hemorrhage than those treated with repeat fibrinolysis (1.3%) or medical therapy (0.5%) (p = .046)

Hypercoaguable Disorders
In general, warfarin therapy can be switched to LMWH 3 to 5 days prior to cardiac surgery. 
Anticoagulation using UFH as a bridge should be resumed as soon as the bleeding risks associated with cardiac surgery have been stabilized, usually within 2 to 3 days postoperatively. 
The patients at highest risk for venous thrombosis are those within 3 months of an episode of thrombosis and those with conditions that predispose to the highest risk of thrombosis, such as antithrombin deficiency

Atrial Fibrilasi
10% to 40% of patients after CABG and in up to 65% of patients undergoing combined CABG and valve surgery.42–45
24 to 48 hours after surgery, considered benign and self-limited, 
associated with prolonged hospitalization, hemodynamic instability, and thromboembolization. 
the risk of stroke increases 3-fold 
(25% to 80%) spontaneously convert to sinus rhythm within 24 hours.

The mechanism 
-multiple wavelet reentry in the atria, 
-rapid firing of an atrial focus, and less likely 
-atrial ischemia.Preoper

predictors 
- age, history of hypertension, male sex, and a previous history of atrial fibrillation and congestive heart 
- aortic cross-clamp time, pulmonary vein venting, respiratory disease, and prolonged ventilation

-The prophylactic use of beta-blocker therapy decreases the incidence of post–CABG atrial fibrillation by as much as 70% to 80%.
-amiodarone in decreasing the incidence of postoperative atrial fibrillation when started one week prior to surgery and continued until hospital discharge.
-Sotalol, a class III antiarrhythmic 
-prophylactic continuous atrial overdrive pacing via temporary epicardial wires or from the right atrium

Carotid Artery Diseases
 -Approximately 1% to 6% of persons develop neurologic complications after cardiac surgery.
-Cerebral microembolization from the arterial tree during CABG is likely the most common culprit. 
-atherosclerosis of the ascending aorta is an independent predictor of long-term neurologic insult and mortality.
-patients undergoing CABG, the incidence of carotid artery disease can be as high as 22% (3% in unselected populations), depending on multiple factors including screening method, age, diabetic status, the presence of left main disease or left ventricular dysfunction, female sex, and a history of smoking or prior cerebrovascular attacks
-perioperative stroke risk is believed to be highest (>5%) in patients with more than 80% unilateral stenosis, bilateral stenoses of at least 50%, and unilateral occlusion with at least a 50% carotid artery lesion on the contralateral side.
Consequently, all patients who fall into one of these categories should be considered for combined carotid endarterectomy (CEA) and CABG. 
-Several authors report operative mortalities between 0% and 5%, and perioperative neurologic and myocardial events of approximately 3%.89–93 At 5 years, over 85% of these patients are stroke free 
-combined CABG/CEA is recommended in symptomatic patients with carotid artery stenosis. 
-Although perioperative myocardial infarction and mortality are generally higher with combined CABG/CEA than with CABG alone, the former is still preferred in this group. 
-no demonstrated difference in mortality or morbidity whether CEA is done before or during CABG.
-Carotid artery stenting can also be. performed in close proximity to CABG. Potential advantages of carotid artery stenting include minimizing the need for systemic heparinization prior to CABG. At present, stenting can be safely performed 4 weeks prior to CABG. Thus carotid artery stenting might be advantageous in patients with stable carotid and coronary disease, in elderly patients who are at high risk for thoracotomy, and in patients who have concomitant carotid artery disease and single-vessel left anterior descending artery disease for which minimally invasive surgery is planned. .

Perioperative Myocardial Protection

Key points

*

Myocardial protection refers to all strategies that increase the heart's ability to withstand an ischaemic insult.

*

Stunning is potentially life-threatening post-ischaemic myocardial impairment after blood flow is fully restored.

*

Hibernation is a prolonged state of reduced myocardial contractility in response to arterial insufficiency such that oxygen demand matches oxygen supply.

*

Volatile anaesthetic agents possess cardioprotective properties independent of their beneficial effect on myocardial oxygen balance.

*

There is good evidence that perioperative use of β-blockers, statins, and α2-agonists reduce perioperative myocardial mortality

-------------------------------------------------------------------------------------

Myocardial protection refers to all strategies that increase the heart's ability to withstand ischaemic insult, which together with reperfusion injury are principally responsible for cardiac morbidity and mortality after high-risk surgery. The bloodless and motionless operating conditions required for cardiac surgery is an environment diametrically opposed to the metabolic demands of the heart.

Pathophysiology of myocardial reperfusion

Ischaemia of sufficient duration results in cell death. However, should the ischaemic insult be interrupted at an appropriate point, a patient will be left with viable myocardium while experiencing a spectrum of detrimental sequelae including arrhythmias and a low cardiac output state. This is directly consequent to the reperfusion injury. Should outright cell death be averted, there are two possible alternatives, that is, stunning and a state of hibernation.

In 1975, it was demonstrated that 15 min of coronary occlusion resulted in 6 h of left ventricular depression, leading Braunwald and Kloner to state that ‘transient ischaemia may interfere with normal myocardial function, biochemical processes, and ultra-structure for prolonged periods’. Stunning is a commonly encountered phenomenon characterized by potentially life-threatening post-ischaemic myocardial impairment after coronary blood flow has been fully restored. It can be overcome by inotrope therapy or calcium infusions without negative consequences and has a duration of hours to days. Examples of stunning would be unstable angina or after aortic cross-clamping during cardiac surgery.

The mechanism underlying stunning is thought to be a combination of cytosolic calcium overload which, if prevented, abolishes this phenomenon and the development of oxygen free radicals. Severe cellular damage has been demonstrated when an anoxic heart preparation is re-exposed to oxygen. Calcium overload may damage the myocyte contractile apparatus in ways that impair its normal response to calcium. Suggested sources of calcium include entry through voltage-sensitive calcium channels, decreased uptake into the sarcoplasmic reticulum, impaired sodium–calcium exchange due to decreased cytosolic pH, and activation of the calcium release channel of the ryanodine receptors. During a hypoxaemic episode, electrons form damaging free radicals instead of passing down the energy gradient of the electron transport chain. The hydroxyl group in particular is thought to play a significant role in the lipid peroxidation of cell membranes leading to increased permeability to calcium.

Hibernation was first described by Rahimtoola as ‘a state of persistently impaired myocardial and left ventricular function at rest due to reduced coronary blood flow that can be partially or completely restored to normal if the myocardial oxygen supply/demand relationship is favourably altered, either by improving blood flow and/or by reducing demand’. The ‘smart heart’ has down-regulated mechanical activity to a level at which aerobic metabolism functions normally. Current theories suggest that hibernation is the consequence of serial episodes of ischaemia, possibly silent, causing repeated stunning. Tumour necrosis factor-α signals structural changes that in part parallel disuse atrophy and include loss of myofibrils, accumulation of collagen and fibroblasts, and loss of mitochondria.

Hibernation is reversed by revascularization and the scope for potential improvement in ventricular function can be examined by a number of means including positron emission tomography (PET) and dobutamine stress echocardiography. Mismatch of myocyte utilization of labelled deoxyglucose relative to blood flow indicates hibernating tissue on PET scanning whereas a positive echocardiographic response to inotropy suggests viability with dobutamine stress examination.

Temperature and haemodynamic modulation

In addition to being the primary mode of cerebral protection, hypothermia also offers myocardial protection. It achieves this by promoting electromechanical inactivity, impeding the process that results in apoptosis, and perhaps most importantly by reducing oxygen consumption. The lowest oxygen demands occur when the heart is arrested and decompressed. At 22°C, myocardial oxygen consumption is reduced from 80 to 0.3 ml 100 g−1 min−1.1 Increases in wall tension, contractility, and heart rate all serve to increase myocardial oxygen demand. Laplace's law for a sphere states that the wall tension (σ) is proportional to the internal pressure (P) and internal radius (r), and inversely proportional to the wall thickness (η)

Thus, we see a direct relationship between radius and wall tension that provides the rationale behind several haemodynamic interventions available to the surgical team all aimed at reducing ventricular wall tension. Venting of the left side of the heart via a catheter is an effective technique for cardiac decompression and air removal and has the added advantage of providing a dry operative field. The left ventricular vent catheter can be inserted during the surgical procedure via various routes such as the ascending aorta, a right-sided pulmonary vein, or the left ventricular apex. The aim is to maintain a low ventricular wall tension. Separation from cardiopulmonary bypass while the heart is relatively empty offers the same advantage but requires careful observation and incremental filling to maintain an adequate preload.

Cardioplegic techniques

Cardioplegic diastolic arrest and hypothermia currently form the foundation of protective practice for on-pump cardiac surgery. Other interventions such as anaesthetic preconditioning (APC) and several novel strategies are worthy of discussion. Widespread in use, cardioplegia was introduced as a concept by Lamb in 1958. Cardioplegia may be blood or crystalloid, warm or cold, and continuous or intermittent. The main component of cardioplegic solutions responsible for inducing diastolic cardiac arrest is potassium, and concentrations in the order of 20 mmol litre are required. Blood is superior at preserving myocyte and endothelial function resulting in reduced incidence of mortality, myocardial infarction, and left ventricular failure in high-risk patients.2 A recent meta-analysis demonstrated reduced incidence of low cardiac output syndrome in the blood cardioplegia arm.3 Compared with crystalloid cardioplegia, blood offers several attributes that may contribute to the above clinical findings. In addition to the potential oxygen carrying ability, blood offers delivery of other nutrients, and also an inherent buffering ability and scavenging of oxygen free radicals. Note that the haemoglobin content of blood used for cardioplegia is diluted to around 5 g dl−1 and its p50 on the oxygen haemoglobin dissociation curve is displaced to the left. This will decrease potential oxygen delivery to the myocardium significantly.

Cardioplegia can be delivered in antegrade or retrograde fashion. The former provides quick arrest and good left ventricular protection and is undertaken by infusing the solution into the aortic root proximal to the aortic cross-clamp. A competent aortic valve is required in order for the cardioplegia to perfuse the coronary arteries and to prevent detrimental left ventricular dilation. Retrograde cardioplegia is applied through a specific cannula into the coronary sinus and requires venting of the aortic root. This may reach parts of the myocardium inadequately perfused by the coronary arteries but may be insufficient for right ventricular protection as a sole technique.

The optimal composition for cardioplegia is a subject of continued research. It should be slightly hyperosmolar to limit oedema, alkalotic to attenuate subsequent pH changes, and have a low calcium concentration. The basic recipe can be complemented by a variety of substances aiming to provide metabolic substrates and enhanced cellular protection. Addition of aspartate and glutamate improves left ventricular stroke work index, increases myocardial oxygen consumption, and improves metabolic recovery. Metabolic enhancement with insulin and glucose has recently demonstrated trends towards improved functional recovery in patients undergoing coronary artery bypass grafting (CABG). Adding the vasodilator and metabolic precursor adenosine has also demonstrated promising trends in a variety of clinically relevant endpoints. Other possible additives include magnesium, the nitric oxide precursor l-arginine, N-acetylcysteine, nicorandil, and bupivacaine.

The temperature at which cardioplegia is administered can be divided into cold (5–10°C), tepid (27–30°C), and warm (37–38°C). Low temperatures may be conducive to ischaemic protection but may accentuate the reperfusion injury. Evidence exists to suggest that warm cardioplegia is associated with reduced postoperative CK-MB increase (12.3% vs 17.7%) and a reduced hospital stay (6 vs 9 days). The authors of this study did, however, warn that interruption to the continuous administration of warm cardioplegia renders the myocardium susceptible to warm ischaemic injury. Surgeons who prefer intermittent administration of cardioplegia might adopt a regimen consisting of inducing arrest with warm cardioplegia and then providing maintenance with cold. Alternatively, an infusion of warm cardioplegia or warm blood only, via the cardioplegia cannula towards the end of the procedure (hot shot), has its advocates. Evidence to date suggests that, on balance, tepid cardioplegia provides the best overall protection and recovery.

Ischaemic preconditioning

Preconditioning describes the remarkable phenomenon whereby exposure to a physical or pharmacological stimulus reduces subsequent injury from ischaemia. This is analogous to the reduced infarct size seen in a myocardial infarct after frequent angina. Postconditioning is similar, but the stimulus occurs at the end of the insult. Remote ischaemic preconditioning (RIPC) happens after reperfusion of a limb or organ, distant from the myocardium, which underwent a period of ischaemia. The concept of preconditioning can be broadly divided into ischaemic preconditioning (IPC) and APC.

IPC was first described in dog hearts in 1986. In these experiments, hearts were subjected to four short episodes of ischaemia separated by 5 min of perfusion before being subjected to a 40 min ischaemic insult. Preconditioning reduced the size of the resultant infarct from 30% to 7%.4 IPC is divided into early (classical) and late, with differing mechanisms that explain the different chronology. Early preconditioning starts within 15 min and lasts for several hours. It protects against myocardial infarction but not stunning. The speculative mitochondrial hypothesis for preconditioning proposes adenosine as one of several possible triggering agents that activates phospholipase C leading to increased expression of protein kinase C. This subsequently phosphorylates and hence activates the final target, that is, mitochondrial ATP-sensitive potassium channels (KATP). Drugs such as the sulphonylureas, which act by blocking KATP channels, may inhibit the preconditioning effect. Recent evidence suggests that patients with non-insulin-dependent diabetes mellitus and coronary heart disease may benefit from changing their treatment perioperatively to insulin.5 Thyrosin kinase and mitogen-activated protein kinases are also involved. Other potential triggers include acetylcholine, opioids, and bradykinin. Opening of these channels protects the mitochondria from calcium overload.

Late preconditioning reflects a second delayed window of protection, which starts at around 12 h and lasts up to 4 days. It protects against both myocardial infarction and stunning. This phenomenon involves the development of an altered myocardial cell structure which is dependent on stress responsive gene transcription leading to the synthesis of cardioprotective proteins, including most importantly cyclooxygenase-2 and inducible nitric oxide synthase. Less important examples are superoxide dismutase and heat-shock proteins that are able to stabilize the cytoskeleton. The collective activity of these proteins results in reduced apoptosis.6

Anaesthetic preconditioning

Over a quarter of a century ago, reduced ST segment elevation was demonstrated in dog hearts exposed to brief ischaemic episodes in the presence of halothane. Unfortunately, subsequent concerns regarding the risk of ‘coronary steal’ with isoflurane anaesthesia took precedence. Coronary steal is postulated to occur in the presence of coronary vasodilators acting on normal vasculature and depriving tissue supplied by atherosclerotic vessels of blood, as these are less able to dilate. It was thought to be a particular risk in ‘steal-prone’ anatomy, defined as being the complete occlusion of one coronary artery that is supplied distally by collateral flow from another coronary artery with >50% occlusion. In clinically relevant concentrations, this has been shown not to be the case. It is now appreciated that all currently used volatile agents are cardioprotective and that this property extends to ischaemic tissue. In addition to the indirect cardioprotective properties of negative inotropy and chronotropy that result in a beneficial effect on myocardial oxygen balance, volatile anaesthetic agents have a direct cardioprotective effect that strongly resembles IPC

APC involves exposure of the myocardium to halogenated inhalation anaesthetics in order to attenuate the subsequent injury due to ischaemia and reperfusion. As low as 0.25 minimum alveolar concentration (MAC) may be protective, but the maximum effect is achieved at 1.5–2 MAC. It is also associated with an early and a late or memory effect. This technique avoids the risk and practical difficulty of exposing diseased myocardium to transient ischaemia. Evidence now exists suggesting that volatile agents also exert a renal, cerebral, and hepatic preconditioning effect. The extracellular signalling pathways responsible for this effect are very similar to those seen in IPC and involve signalling substances binding to inhibitory G-protein-coupled receptors to trigger several intracellular pathways. Intracellular protein kinase C plays a central role in the mechanism leading to opening of mitochondrial KATP channels. Production of mitochondrial reactive oxygen species (ROS) is increased via partial inhibition of complex III of the electron transport chain, which activates signalling pathways for preconditioning resulting in less ROS production on reperfusion. Mitogen-activated protein kinase and adenosine receptor activation are also involved. In a recent meta-analysis involving slightly <3000 patients undergoing CABG surgery, APC significantly lowered troponin I concentrations, reduced inotrope requirement, reduced duration of hospital stay, and was associated with 20% greater cardiac indices. However, it did not reduce the incidence of perioperative myocardial infarction or mortality.

Halogenated volatile agents are not the only pharmacological agents capable of eliciting pharmacological preconditioning. Xenon, adenosine, nicorandil, and norepinepherine among others also have preconditioning properties. Morphine is a preconditioning agent, which in addition has synergistic activity with volatiles. As this effect is mediated via the delta receptor, other opioids used in anaesthesia do not demonstrate this property. Ageing, diabetes, and hypercholesterolemia all attenuate APC.

Postconditioning and remote ischaemic preconditioning

Ischaemic postconditioning is the interruptive reperfusion at completion of cardiac surgery. This might consist of repeated sequences of perfusion for 30 s followed by re-occlusion for 30 s. It has been found to significantly reduce infarct size in patients undergoing angioplasty for complete coronary artery occlusion. Volatile agents also have a postconditioning effect possibly mediated by inhibition of the neutrophil-mediated ROS generation responsible for reperfusion injury.

RIPC involves inducing ischaemia distant to the myocardium in tissues such as the mesentery, kidney, or lower limb in order to obtain a myocardial protective effect after reperfusion of the remote tissue. An example is 5 min of renal artery occlusion before coronary artery reperfusion; this also has demonstrated reduction in the extent of infarct. A recent study of RIPC in patients undergoing elective abdominal aortic aneurysm repair found a 27% reduction in myocardial injury, a 22% reduction in myocardial infarction, and a 23% reduced incidence of renal impairment.7 Both remote conditioning and postconditioning are mediated by adenosine which reduces inotrope requirement, ICU stay, and significant reductions in troponin I release. Volatile anaesthetic agents also possess postconditioning properties which, as in preconditioning, results in the opening of ATP-sensitive potassium channels preventing mitochondrial calcium overload.

Pharmacotherapy

Postoperative myocardial infarction has a mortality of ∼10%. It is often silent, non-Q-wave, and preceded by ST depression. It normally occurs within a few hours of completion of surgery and is associated with tachycardia and hypertension, which, as previously discussed, are factors contributing to increased myocardial oxygen demand. β-blockade reduces mortality after myocardial infarction in proportion to the reduction in heart rate. The influential Mangano and colleagues, and Poldermans and colleagues trials have demonstrated reduced myocardial infarction and mortality after major non-cardiac surgery in β-blocked patients. However, for a variety of reasons, these trials have courted criticism. A meta-analysis of six randomized controlled trials found that β-blockade was associated with a 75% reduction in the risk of perioperative cardiac death. The benefits of β-blockers are not confined to non-cardiac surgery as their use has also been shown to reduce 30 day mortality after CABG.8 The benefits of perioperative β-blockade may be more pronounced in patients with risk factors for ischaemic events.

The α2-agonists clonidine and mivazerol have demonstrated perioperative myocardial protective properties. In patients with known coronary artery disease, mivazerol reduces the incidence of myocardial infarction and overall mortality rate in general surgical and vascular patients. Clonidine after operation significantly reduces myocardial ischaemia in vascular patients.

The statin family of drugs offers both lipid lowering and a complex collection of unrelated or ‘pleotropic’ benefits, including increased plaque stability, decreased platelet activity, decreased inflammatory markers, and improved arterial blood flow. Patients receiving statins at the time of surgery enjoy a reduction in all-cause mortality, myocardial infarction, and cardiovascular mortality.9 The reduced mortality has been shown to extend up to 5 yr after operation. Like β-blockers, the benefit may be greater in higher risk patients.

Other strategies

Meta-analysis has demonstrated that despite the sound theoretical reasoning of improved analgesia and reduced stress response to surgery, thoracic epidural analgesia and intrathecal analgesia do not reduce the incidence of mortality or myocardial infarction.10 It has recently been shown that a glucose–insulin–potassium infusion in non-diabetics reduces myocardial damage and inotrope requirements. The potential antioxidant properties of propofol remain controversial with a recent study comparing large-dose propofol (100 µg kg−1 min−1) with isoflurane and finding a reduced inotrope requirement and myocardial injury. Antibody therapy to prevent P-selectin and intercellular adhesion molecule-1 activation may attenuate leucocyte-mediated reperfusion injury and is associated with reduced infarct size in animal models.

Conclusion

The ageing and more expectant population with increasing morbidity provides continued impetus to develop the practice of a myocardial preservation management system. The role of hypothermia is increasingly controversial in the light of the fact that diastolic arrest provides the majority of protection derived from reduced oxygen demand. An increased understanding of the mechanisms involved in myocardial injury will lead to an increased application of pharmacotherapy to prevent them. Volatile anaesthetic agents and morphine posses direct and synergistic cardioprotective effects, independent of their beneficial effects on myocardial oxygen balance. The American College of Cardiology and American Heart Association recommend that patients with a requirement for β-blockers to manage angina or hypertension and patients at risk for ischaemic heart disease should be titrated to a heart rate of 50–60 beats min−1. This may protect against ischaemic events. It also suggests that the α2-agonists may offer similar protection.