MECHANISM OF THE PROTECTIVE EFFECT OF WHOLE-BODY HYPOTHERMIA FOLLOWING CORONARY ARTERY OCCLUSION
Abstract
Salvaging ischemic myocardial tissue is of utmost importance in preventing myocardial pump failure and death. Restoring myocardial blood flow, by coronary revascularization, is a definitive treatment which reverses the fundamental lesion of coronary occlusion. However, in order to protect myocardial tissue and prevent heart failure, blood flow must be restored before extensive irreversible damage occurs. Since delay is inevitable between the occurrence of coronary artery occlusion and the restoration of blood flow, a therapy which limits the amount of injury incurred during this period would be a valuable presurgical adjunct to coronary revascularization. This study presents evidence that whole-body hypothermia decreases the amount of irreversible myocardial injury sustained during this period without compromising blood flow to the non-ischemic region of the heart which is responsible for maintaining adequate cardiac output. A mechanism by which hypothermia exerts its protective effect is also proposed. This study was performed to evaluate the effects of myocardial infarction and hypothermia, alone and in combination, on regional myocardial blood flow, myocardial damage, and the hemodynamic state of subjects over a five hour period. Regional blood flow was determined by a radioactive tracer microsphere technique. Myocardial damage was measured by a gross histochemical staining method using nitrobluetetrazolium (NBT). Heart rate, mean arterial blood pressure, and cardiac output were measured to evaluate the hemodynamic state of the animals. Four experimental groups representing different treatment combinations were employed. The group of primary interest is the hypothermic/infarcted group in which the left anterior descending (LAD) coronary artery was ligated in dogs subsequently cooled from 39(DEGREES) to 26(DEGREES)C. The other three groups; normothermic/infarcted, normothermic/sham, and hypothermic/sham; provide control values with which to compare the data obtained from the hypothermic/infarcted group. Together these groups represent a nested factorial design in which 20 dogs are nested, in groups of 5, within each of the 4 experimental treatments. All animals were treated identically, except for the specific treatment applied; i.e. normothermic versus hypothermic, and occlusion versus sham occlusion of the LAD coronary artery. The time of the occlusion (or sham) was considered to be t(,o) for the experiment. Blood flow was determined 4 times during the experiment by injecting 1 of 4 differently labelled radioactive microsphere suspensions. Microspheres were injected 15 min prior to, and 0.5, 2.0, and 5.0 hours after, t(,o). Heart rate, arterial blood pressure, and core body temperature were monitored continuously. Five minutes after the final microsphere injection, the heart was excised. The left ventricle was sliced for NBT staining. Following staining, the heat was further subdivided for determination of regional blood flow by gamma radiation counting. The results indicate that initiating whole-body hypothermia soon after the onset of coronary occlusion decreases permanent myocardial injury. Since hypothermia did not improve blood flow to the ischemic region, its apparent mode of action is to reduce demand for blood flow. The finding that the hemodynamic variables exhibited no significant difference between the hypothermic/sham and hypothermic/infarcted groups suggests that hypothermia did not produce or exacerbate cardiogenic shock which may accompany acute myocardial infarction. Finally, the finding that hypothermic and normothermic non-ischemic myocardium respond similarly, following occlusion, by increasing blood flow does not support the hypothesis that hypothermia may cause secondary ischemia or infarction during cardiac surgery. These results support the proposal that whole-body hypothermia could be a safe, effective preoperative therapy for coronary revascularization.
Degree
Ph.D.
Subject Area
Anatomy & physiology|Animals
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