LABORATORY INVESTIGATION MYOCARDIAL INFARCTION Myocardial salvage by intravenous nitroglycerin in conscious dogs: loss of beneficial effect with marked nitroglycerin-induced hypotension

We studied the effect of nitroglycerin-induced decreases in mean arterial pressure (MAP) on myocardial salvage. Two hours after occlusion of the left anterior descending coronary artery, 65 conscious dogs were randomly allocated to receive 4 hr intravenous infusions of saline (group 1, 19 dogs), or nitroglycerin in doses to decrease MAP by 10% (group 2, 18 dogs), 25% (group 3, 14 dogs), and 50% (group 4, 14 dogs), respectively. At 7 days, 41 dogs were killed for measurement of infarct size; 24 dogs, given 7 to 10 gm radioactive microspheres for flow calculations, were killed 6 hr after occlusion. Boundaries of the occluded bed were defined by postmortem coronary arteriography. Infarct and occluded bed masses were measured by planimetry of weighed transverse sections of the left ventricle. Compared with saline infusions in group 1, nitroglycerin infusions produced sustained reductions (p < .001) in mean left atrial pressure and MAP in all dogs, but heart rate was unchanged. The decreases in MAP achieved in groups 2, 3, and 4 were 10% (range, 5% to 19%), 23%, and 39%, respectively, with average levels of 96 (range, 83 to 113), 83, and 64 mm Hg, respectively. Despite similar masses of the occluded bed and left ventricle among the four groups, infarct size was significantly smaller (p < .025) in group 2 compared with groups 1, 3, or 4, expressed both as percent of the left ventricle (6% vs 14% vs 13% vs 15%) and as percent of the occluded bed (13% vs 37% vs 34% vs 44%). Myocardial salvage (expressed as percent of the occluded bed) with nitroglycerin correlated inversely with the percent of decrease in MAP (r = .77, p < .001). Collateral blood flow increased (p < .005) throughout the occluded bed in group 2 compared with group 1 but was unchanged in groups 3 and 4. In contrast, coronary vascular resistance decreased (p < .025) in all nitroglycerin groups. These results suggest that perfusion pressure is an important determinant of myocardial salvage during nitroglycerin therapy. An increase in the dose of nitroglycerin to decrease MAP by more than 10%, and to levels below 96 mm Hg, might offset its potential for myocardial salvage in the conscious dog. Circulation 68, No. 3, 673484, 1983. THE BENEFICIAL EFFECTS of intravenous nitroglycerin infusion on ischemic injury in early stages of myocardial infarction in dogslA have brought about its use in patients with acute infarction.>'2 After occlusion of the left circumflex coronary artery in conscious dogs, nitroglycerin has been shown to decrease infarct size and increase collateral blood flow when mean arterial pressure (MAP) dropped by 10% (from 115 to 103 mm Hg). 13 In another study, after the left anterior From the Cardiology Division of the Department of Medicine and the Surgical and Medical Research Institute, University of Alberta, Edmonton, Alberta. Supported in part by grants from the Medical Research Council of Canada. Address for correspondence: Dr. B. I. Jugdutt, 6-112, Clinical Sciences Building, University of Alberta, Edmonton, Alberta, Canada T6G 2G3. Received March 1, 1983; revision accepted April 28, 1983. Presented in part at the Scientific Sessions of the Annual Canadian Cardiovascular Society Meeting in Calgary, October, 1982. descending artery (LAD) was occluded in conscious dogs, nitroglycerin increased collateral blood flow but did not reduce infarct size when MAP was dropped by 16% (from 103 to 84 mm Hg).'4 It is well recognized that coronary perfusion pressure is a major factor in determining collateral blood flow'5 and limiting infarct size.'6 Since nitroglycerin dilates systemic and coronary vessels, it is possible that the dilated coronary bed in ischemic regions becomes critically dependent on coronary perfusion pressure during nitroglycerin infusion. This study was performed to determine the effects of three levels of nitroglycerin-induced hypotension on myocardial salvage and collateral blood flow.