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Approaches to the Prevention of Perioperative Myocardial Ischemia

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Approaches to the Prevention of Perioperative Myocardial Ischemia 253 m CLINICAL CONCEPTS AND COMMENTARY Richard B. Weiskopf, M.D., Editor Anesthesiology 2000; 92:253–9 © 2000 American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins, Inc. Approaches to the Prevention of Perioperative Myocardial Ischemia Downloaded from http://pubs.asahq.org/anesthesiology/article-pdf/92/1/253/398628/0000542-200001000-00038.pdf by guest on 25 September 2021 David C. Warltier, M.D., Ph.D.,* Paul S. Pagel, M.D., Ph.D.,† Judy R. Kersten, M.D.† PREVENTION of perioperative myocardial ischemia is on the horizon promise to reduce the risk of myocardial essential to avoid the mechanical, metabolic, and elec- ischemia or infarction. Although some of these new trophysiologic changes associated with acute imbal- drugs act by altering the myocardial oxygen supply/ ances in the relationship between myocardial oxygen demand relationship, others directly protect myocar- supply and demand. Myocardial ischemia of sufficient dium from ischemic injury. This brief review outlines severity or prolonged duration may result in reversible established methods used for the prevention of myocar- (e.g., myocardial stunning) or irreversible (e.g., infarc- dial ischemia and also discusses potential future thera- tion) damage, malignant ventricular arrhythmias, or car- peutic strategies that may attenuate the reversible and diogenic shock. These potentially disastrous conse- irreversible sequelae of ischemia. At present, the major- quences are associated with high morbidity and ity of data has been obtained in patients with severe mortality in patients with coronary artery disease. Elec- coronary artery disease undergoing coronary artery by- pass graft surgery. The applicability of results obtained in tive surgical procedures may be delayed until unstable this patient population must be extrapolated with care coronary artery disease is treated by angioplasty or sur- to patients with less severe coronary disease or those gical revascularization. undergoing noncardiac surgery. Despite the prevalence of coronary artery disease and the frequent occurrence of myocardial ischemia, the anesthesiologist may implement important pharmaco- Myocardial Oxygen Supply and Demand logic and anesthetic interventions that improve periop- erative outcome. In addition, several exciting new drugs The classical relationship between myocardial oxygen supply and demand indicates that when oxygen demand exceeds supply, the imbalance results in myocardial * Professor, Departments of Anesthesiology, Pharmacology and Toxicol- ogy, and Medicine; and Vice Chairman, Research of Anesthesiology. ischemia (fig. 1). Fortunately, this supply/demand rela- † Associate Professor, Department of Anesthesiology. tionship may be favorably altered by a variety of phar- macologic agents in the perioperative period to prevent Received from the Departments of Anesthesiology, Pharmacology and Toxicology, and Medicine, the Medical College of Wisconsin and the onset of myocardial ischemia. Such interventions the Zablocki Veterans Affairs Medical Center, Milwaukee, Wisconsin. should be aggressively undertaken in a manner equal to Submitted for publication April 19, 1999. Accepted for publication July the vigilance required for the detection of acute isch- 24, 1999. Supported in part by grants no. HL 54280 (to Dr. Warltier) emic events. Objectives of treatment include reducing and HL 03690 (to Dr. Kersten), and Anesthesia Research Training grant demand for oxygen by myocardium at risk for develop- no. GM 08377 (to Dr. Warltier) from the United States Public Health Service, Bethesda, Maryland. ment of ischemia while simultaneously increasing oxy- Address reprint requests to Dr. Warltier: Medical College of Wiscon- gen supply to this tissue. Myocardial oxygen demand in sin, MEB—Room 462C, 8701 Watertown Plank Road, Milwaukee, Wis- the left ventricle is dependent on heart rate, myocardial consin 53226. Address electronic mail to: [email protected] contractility, and ventricular loading conditions. Heart b Key words: -Blockers; coronary artery disease; KATP channels; vol- rate is the most important of all physiologic factors that atile anesthetics. can be altered to reduce demand. Increases in heart rate The illustrations for this section are prepared by Dmitri Karetnikov, not only lead to profound increases in oxygen consump- 7 Tennyson Drive, Plainsboro, New Jersey 08536. tion but also jeopardize perfusion in regions distal to Anesthesiology, V 92, No 1, Jan 2000 254 WARLTIER ET AL. Fig. 1. (A) Representation of oxygen de- mand exceeding supply, resulting in ischemic sequelae. Note that traditional approaches to this problem address Downloaded from http://pubs.asahq.org/anesthesiology/article-pdf/92/1/253/398628/0000542-200001000-00038.pdf by guest on 25 September 2021 myocardial oxygen balance. In con- trast, new cardioprotective therapies may not prevent an ischemic episode, but instead reduce the metabolic, me- chanical, and electrophysiologic conse- quences of ischemia. (B) Mechanisms by which b-adrenoreceptor antagonists improve balance of myocardial oxygen supply and demand. Arrows indicate di- rectional changes produced by b-block- ers. CBF 5 coronary blood flow. coronary artery stenoses by reducing the duration of between aortic diastolic and left ventricular end-diastolic diastole. These actions are most pronounced in the left pressures) gains greater significance. Myocardial blood ventricular subendocardium. As stenosis severity in- flow is autoregulated to a relatively constant level under creases, and with it the risk of ischemia and infarction, normal conditions, but the ability of the distal coronary the role of coronary perfusion pressure (the difference vascular bed to dilate in response to increasing stenosis Anesthesiology, V 92, No 1, Jan 2000 255 PERIOPERATIVE MYOCARDIAL ISCHEMIA severity will eventually become exhausted. Finally, in ultimately place the patient at far greater risk for devel- the presence of severe stenosis, autoregulation fails to opment of complications because treatment of pro- maintain coronary blood flow, and perfusion to the af- tracted myocardial ischemia and its consequences is in- fected territory becomes directly dependent on coronary herently more difficult than primary prevention of perfusion pressure. Deleterious increases in myocardial ischemia. Prophylaxis against myocardial ischemia is of contractility and oxygen use may occur during the peri- the utmost importance for the patient with coronary b b operative period because of 1-adrenoceptor stimulation artery disease, and the use of -adrenoceptor antagonists Downloaded from http://pubs.asahq.org/anesthesiology/article-pdf/92/1/253/398628/0000542-200001000-00038.pdf by guest on 25 September 2021 by endogenous catecholamines. Left ventricular preload to achieve this goal has a firm scientific basis that may and afterload also affect myocardial oxygen demand by well exceed the relative importance of the type of anes- altering end-diastolic and end-systolic wall tension, re- thetic chosen for the patient at risk. spectively. Many other factors, such as blood rheology, hematocrit, and coronary collateral blood flow, influ- ence the myocardial oxygen supply/demand relation- Pharmacologic Prophylaxis ship as well. The degree to which any of these factors may result in myocardial ischemia is specific for each Administration of b-adrenoceptor antagonists (using patient. Small decreases in coronary perfusion pressure the protocol of Mangano et al.1) to patients with coro- or increases in heart rate may produce detrimental ef- nary artery disease undergoing surgery has been recom- fects depending on the specific degree of coronary ar- mended by the American College of Physicians. To date, tery disease. Thus, clinical investigations of frequency of b-adrenoceptor antagonists are the only well-established and morbidity associated with ischemia during anesthe- means of prophylaxis against myocardial ischemia that sia are difficult to conduct. The severity of coronary demonstrate a reduction of morbidity and mortality in artery disease represents a major confounding variable this patient population. Atenolol has been shown to be that is difficult to control during clinical investigations. antiischemic, protect against myocardial reinfarction, For example, a large increase in heart rate may be well and reduce overall mortality caused by cardiac death and tolerated in a patient with mild coronary artery disease. congestive heart failure in both the immediate and re- In contrast, a small increase in heart rate may be accom- mote perioperative periods.1,2 The investigation by Man- panied by global deterioration of left ventricular function gano et al.1 has been criticized because of differences in secondary to profound ischemia in a patient with severe the preoperative and postoperative medical manage- multivessel disease. ment of study groups, i.e., the group treated with b-ad- Traditional pharmacologic approaches to the preven- renergic antagonists had more aggressive medical man- tion and treatment of ischemia focus on the oxygen agement before surgery and possibly afterward as well. supply/demand relationship; however, novel therapeu- Nevertheless, this study demonstrates the efficacy of tic strategies are being studied intensively. Newer mo- b-blockers in patients undergoing noncardiac surgery. dalities may alter myocardial oxygen demand at the cel- Selective dosing of b-adrenoceptor antagonists may ex- lular or mitochondrial level independent of systemic and ert greater benefits than arbitrary,
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