Dhun H. Sethna

The Coronary Circulation and Myocardial Oxygenation in Coronary Artery Disease: Effects of Anesthesia

The companion review to this article, published in last month’s issue of Anesthesia and Analgesia, has already examined the coronary circulation, its anatomy and physiology, hemodynamics and regulation of normal coronary flow, along with alterations in hemodynamics due to coronary stenosis and metabolic indices of myocardial ischemia (52). In this review the patient with coronary arterial disease who must have anesthesia for a cardiac or noncardiac operation is considered. Because of the large number of patients having coronary artery bypass grafting (CABG) and the even larger number with coronary disease having other operations, anesthesiologists must deal with coronary patients regularly. Patients who have had a previous infarction have a higher risk of perioperative reinfarction and death than those without a known infarction (44,62,64). Thus a pertinent subject in anesthesia is how to manage the patient with coronary disease through anesthesia and recovery without incurring infarction. Paralleling the cardiac surgical advances of the last 15 years have been significant strides in the knowledge and clinical skill with which these patients are handled during anesthesia. Introduction of direct monitoring to anesthesia, particularly the pulmonary arterial catheter (63), plus the intravenous opiates (8,16,61) and new inhalational agents (5,7), have contributed to the ability to safely manage these patients through cardiac operations. Since the first

CK-MB Release Following Coronary Artery Bypass Grafting in the Absence of Myocardial Infarction

Elevation of levels of the myocardial-specific isoenzyme of creatine kinase (CK-MB) in the immediate postoperative period in patients undergoing coronary artery bypass grafting is usually associated with myocardial necrosis. However, mean isoenzyme elevations of 18 +/- 2 IU/L (standard error of the mean) were recently observed in 6 patients in the absence of electrocardiographic or scintigraphic (technetium 99m stannous pyrophosphate) evidence of perioperative myocardial infarction. To test the hypothesis that surgical trauma of the atrium and aorta during cannulation for cardiopulmonary bypass might contribute to elevated CK-MB levels, biopsy of the right atrial appendage and aorta of 7 patients was done at operation, the tissue samples were assayed for total creatine kinase (CK) activity using the Rosalki technique, and for CK-MB using column chromatography. The results indicate that the human atrium is a rich source of CK, with the proportion of CK-MB similar to that present in the ventricle (20%). In addition, technical considerations inherent in the performance of coronary bypass surgery may result in release of CK-MB, causing elevated serum enzyme levels in the post-coronary artery bypass patient in the absence of myocardial infarction.

Myocardial metabolism and hemodynamic responses to halothane or morphine anesthesia for coronary artery surgery.

Eighteen patients having coronary artery bypass grafts were randomly anesthetized with morphine (1 mg/kg) or halothane and oxygen. Central and peripheral pressures were measured serially, plus cardiac output and total coronary sinus blood flow, both by thermodilution catheters, starting before induction of anesthesia and continuing until completion of sternotomy. No significant differences in hemodynamic responses were seen between the two anesthetic techniques during induction: blood pressure and peripheral vascular resistance decreased significantly, but not cardiac output or coronary flow. Myocardial oxygen consumption decreased significantly with induction as oxygen content of coronary sinus blood increased, indicating preservation of oxygen balance. Heart rate and blood pressure increased after sternotomy in the patients given morphine, with the myocardium producing lactate in two of six patients and with nitroprusside being required in four patients to decrease arterial pressure. Halothane-oxygen anesthesia effectively controlled autonomic responses to sternotomy, although one of 12 patients had myocardial lactate production at that time. Neither rate-pressure product or ST segment changes were useful predictors of the ratio between myocardial oxygen consumption and supply. Myocardial oxygen balance can be maintained in coronary patients before cardiopulmonary bypass if pulse rate and blood pressure are kept at less than awake levels.

Rate-pressure product correlates poorly with myocardial oxygen consumption during anaesthesia in coronary patients.

In 26 patients having coronary grafts, haemodynamics, coronary sinus blood flow and the arterio-coronary, sinus difference of oxygen content were determined, awake and at four intervals during morphine-oxygen or halothane-oxygen anaesthesia. Rate-pressure product (RPP), triple product (TP) and myocardial oxygen consumption (MVO2) were calculated. The correlation of the two indirect indices to MVO2 were tested by repeated measures and regression analyses. No significant correlations were seen at four of five study times, when outlying data points were appropriately excluded. A pitfall of using more than one data point from each patient in the linear regression analysis is pointed out. In addition to the lack of correlation of RPP to MVO2, RPP was an imprecise predictor of myocardial lactate production and of postoperative infarction.RésuméChez 26 malades opérés pour pontage aorto-coronaire, nous avons mesuré le profii hémodynamique, le flux sanguin du sinus eoronaire e: la différence artérioveineuse en oxygène du sang coronaire, Des mesures ont été faites avant l’anesthésie et à quatre reprises durant une anesthésie à la morphine-oxygène ou halothane-oxygène. Le produit fréquence/pression (RPP) le triple produit (TP) et la consommation d’oxygène par le myocarde (MVO2) ont été calculés. La corrélation des deux index indirects de MVO2 a été vérifié par des mesures répétées et par des analyses de courbe de régression. Aucune correlation significative n’a été démontrée à quatre des cinq stations de mesure, lorsque les données aberrantes ont été exclues des calculs. Dans la discussion, nous exposons le danger qu’il y a d’ introduire pour chaque patient plus d’une donnée dans l’analyse de régression.En plus d’être un panvre indicateur de consommation d’oxygène par le myocarde, le RPP était un informateur imprécis quam à la production de lactate par le myocarde et l’incidence de l’infarctus post-opératoire.

An appreciation of the coronary circulation.

Coronary sinus catheter techniques for evaluation of coronary flow and myocardial metabolism have the drawback that a global sampling method is used to evaluate a regional disease (coronary artery disease). Studies on the coronary circulation are further limited by the fact that interventions acting on the coronary bed may simultaneously modify several of the principal determinants of coronary blood flow. Results are also influenced by differences among species, and whether the coronary vascular bed is normal or pathologically narrowed. Because coronary flow is intimately coupled to myocardial oxygen demand, interpretation of values as abnormal require simultaneous evaluation of some index of myocardial oxygen consumption. Under normal conditions, myocardial flow is predominantly in diastole, and is subject to compromise by factors that abbreviate diastole (e.g., tachyarrhythmias). Autoregulation maintains constant coronary blood flow over a range of perfusion pressures (60-130 mm Hg), and increased flow demands are normally met by coronary vasodilation (coronary flow reserve). In proximal coronary stenosis, this capacity for additional vasodilation may be significantly reduced, and flow to potentially ischemic beds beyond the stenosis may be maintained by collaterals. Pharmacologic coronary vasodilation in this situation can result in coronary steal. When perfusion pressure decreases below the autoregulatory range, or when coronary flow reserve is exhausted early, as in coronary stenosis, flow becomes dependent on mechanical factors including duration of diastole and the perfusion pressure. In these situations, monitoring heart rate and diastolic pressure would allow reasonable assessment of adequacy of coronary flow and myocardial perfusion.

Effects of protamine sulfate on myocardial oxygen supply and demand in patients following cardiopulmonary bypass.

The effect of protamine sulfate on myocardial oxygen supply and demand was studied under clinical conditions in nine patients following cardiopulmonary bypass. Before surgery, the patients had severe coronary artery disease with good ventricular function. The patients required no vasoactive drugs, but only blood volume adjustments when weaned off bypass, and were hemodynamically stable at the time of study. The protamine dose of 196 mg (2.5 mg/kg) was infused over 4 ± 1 minutes. Although modest variation in hemodynamic function occurred in individual patients after administration of protamine, there were no significant hemodynamic alterations for the group. No significant alteration in global myocardial metabolism was observed. Protamine caused a small decrease in measured coronary blood flow, resulting in a corresponding reduction in calculated myocardial oxygen consumption as coronary sinus oxygen content remained unaltered. Myocardial lactate extraction showed no significant alteration. It is concluded that protamine sulfate, given at rapid infusion rates in hemodynamically stable patients, is not associated with an adverse alteration in hemodynamics or global myocardial metabolism.

Cardiovascular effects of morphine in patients with coronary arterial disease.

Large doses of morphine sulfate have been reported to cause myocardial lactate production and reduction in coronary blood flow in animals. Similar effects with clinical doses in man would significantly alter the management of cardiac patients. Eleven adult patients with significant coronary arterial disease and normal left ventricular ejection fraction were studied before and 30 minutes after infusion of morphine (0.25 mg/kg IV). Evaluation of myocardial metabolism showed an increase in coronary sinus oxygen content (p < 0.001) and a reduction in myocardial oxygen consumption. Myocardial lactate extraction was not altered. No change in coronary sinus blood flow was seen. It is concluded that infusion of morphine sulfate, 0.25 mg/kg IV, does not produce global myocardial ischemia in patients with coronary artery disease and normal ventricular function.

Dobutamine and cardiac oxygen balance in patients following myocardial revascularization.

Dobutamine is frequently used in the early postoperative period following myocardial revascularization to improve cardiac output. Seven postoperative adult patients with low output syndrome were studied before and during intravenous dobutamine (mean ± SD: 5.1 ± 2.5 μg/kg/min) infusion. The metabolic effects were evaluated and related to hemodynamic changes. Cardiac index increased 40% (p < 0.05) with an increase in heart rate (p < 0.05) and decreases in systemic vascular resistance and right atrial pressure (p < 0.05). No significant changes occurred in arterial or pulmonary capillary wedge pressures or in stroke volume index. Dobutamine produced a 29% increase in myocardial oxygen consumption which, in these revascularized patients, was accompanied by a 35% increase in coronary blood flow. No significant alteration was observed in coronary sinus oxygen content or in global myocardial lactate extraction. Thus, despite the increased metabolic cost of dobutamine, global myocardial ischemia was not observed.

Role of intravenous verapamil in supraventricular tachyarrhythmias after open-heart surgery

Although the antiarrhythmic effects of verapamil (V) have been studied widely, its role in the treatment of atrial tachyarrhythmias after open-heart surgery (OHS) has not been defined. Accordingly, 22 patients were studied using a double-blind randomized crossover protocol 1 to 6 days after OHS, except for one patient, who was studied 90 days after OHS. Atrial fibrillation was seen in 18 and atrial flutter was observed in four patients. Two doses were used, 0.075 and 0.15 mg/kg (not exceeding 10 mg per dose), depending on the response. A positive response consisted of: conversion to sinus rhythm or heart rate less than 100 beats/minute (bpm). Eleven patients received V as the first drug; the remaining 11 received placebo first. Digoxin had been given to 20 patients (0.5 mg average dose) prior to inclusion in the study. Four patients converted to sinus rhythm within 30 minutes after V and one additional patient did so within 10 seconds of placebo administration. The post treatment heart rate combining both low and high dose response was 85 +/- 18 compared to 128 +/- 23 bpm for placebo (M +/- SD, p less than 0.01). The heart rate remained lower than control 30 minutes after V. Transient hypotension required intravenous fluid in one patient. Thus, V safely and rapidly controls heart rate but is not likely to result in immediate conversion to sinus rhythm in patients after OHS.

Intravenous nitroglycerin and myocardial metabolism during anesthesia in patients undergoing myocardial revascularization.

Although intravenous nitroglycerin has been used to control the hypertensive response during sternotomy in patients undergoing myocardial revascularization, the effects of the drug on myocardial oxygen supply and demand have not been described in this clinical setting. Eight adult patients with good ventricular function (ejection fraction >50%), who were anesthetized for coronary artery bypass, were studied before and after administration of intravenous nitroglycerin (mean dose 12 μg/kg in 6 minutes). Evaluation of myocardial metabolism showed an increase in coronary sinus oxygen content (p < 0.05) and a reduction in myocardial oxygen consumption (p < 0.05), Although mean myocardial lactate extraction and coronary sinus blood flow were not significantly altered in the group as a whole, variations in individual patient responses were observed and are discussed. These direct observations of global myocardial metabolism observed in this study group are similar to the conclusions reached by other investigators using indirect indices of myocardial oxygen supply and demand.