MYOCARDLAL BLOOD FLOW Reduced regional myocardial perfusion in the presence of pharmacologic vasodilator reserve

To determine whether reductions in regional myocardial perfusion at reduced coronary arterial pressures reliably indicate maximal vasodilation of the distal vasculature, coronary autoregulation was studied in open-chest dogs at heart rates of -60 beats/min, a level at which metabolic demand, time-averaged systolic compressive forces, and transmural vasodilator reserve approximate those found under usual resting conditions. Circumflex pressure was controlled with a programmable pressure source. Regional circumflex inflow was 0.56 + 0.04(SEM) mlImin'g-' when circumflex pressure equaled spontaneous aortic pressure and fell to 0.34 + 0.02 ml.min -'gwhen circumflex pressure was reduced to 35 mm Hg. Reductions were similar in each myocardial layer, with endocardial flow falling from 0.68 + 0.04 to 0.39 + 0.03 ml-min `.g During adenosine-induced vasodilation at 35 mm Hg, full-thickness and endocardial flows rose to 0.92 + 0.08 and 1.07 ± 0.10 ml.min'g-', respectively. When coronary pressure was reduced to 25 mm Hg and autoregulation was again operative, full-thickness and endocardial flows fell to 0.28 ± 0.03 and 0.28 ± 0.04 ml min'g'. During adenosine vasodilation at 25 mm Hg endocardial flow did not increase significantly but epicardial reserve remained present. These results indicate that significant reductions in regional myocardial perfusion can occur before pharmacologic vasodilator reserve is exhausted. In the absence of tachycardia, endocardial vasodilator reserve can persist to coronary pressures less than 35 mm Hg, but is ordinarily exhausted before epicardial vasodilator reserve. Circulation 71, No. 2, 370-377, 1985. AUTOREGULATORY reductions in impedance to flow cause coronary flow to be held relatively constant as coronary arterial pressure is reduced at a constant level of myocardial metabolic demand. When vasodilator reserve has been exhausted, coronary flow becomes pressure-dependent and falls rapidly with pressure. Coronary flow in this situation also varies importantly with diastolic period, i.e., heart rate and systolic compressive forces. Because these vary transmurally, subendocardial perfusion is in particular jeopardy.4 An inherent transmural gradient in conductance favoring the subendocardium compensates in part for subendocardial vulnerability,5 6 but is not sufficient to maintain normal inner-outer flow ratios at higher heart rates.7 From the Departments of Medicine and Physiology, State University of New York at Buffalo, and the Erie County Medical Center, Buffalo. Supported by a grant from the American Heart Association with funds contributed from the WNY affiliate, The Alexandrine and Alexander Sinsheimer Fund, and Clinical Investigator Award HLB-01 168, and program-project grant HLB-15194 from the National Heart, Lung, and Blood Institute. Address for correspondence: John M. Canty. Jr., M.D., SUNY/AB Clinical Center, Room CC15, Erie County Medical Center, 462 Grider St., Buffalo, NY 14215. Received Sept. 24, 1984; accepted Oct. 25, 1984. 370 In recent years it has generally been held that a diminution in local flow accompanying a reduction in coronary pressure implies exhaustion of local vasodilator reserve. In animal preparations of coronary stenosis, interventions that increase full-thickness flow but decrease poststenotic pressure have been associated with reductions in subendocardial perfusion, with the latter attributed to a "transmural steal," i.e., the exhaustion of subendocardial vasodilator reserve while subepicardial reserve is still present. 19 Although the concept of earlier exhaustion of subendocardial reserve has been supported by other experimental studies, 10. 1 reductions in resting flow in an animal preparation of a coronary muscle bridge have been difficult to reconcile, since all transmural myocardial layers showed substantial increases in flow when adenosine was infused into the " bridged" artery. 12 Also, Bache and Schwartz'3 have reported full-thickness flows during vasodilation at reduced coronary pressures that exceed usual resting flows at normal pressures. Systematic studies of local vasodilator reserve at low pressures have not been performed, in part because of the difficulties involved in maintaining poststenotic pressure constant under control conditions and CIRCULATION by gest on A ril 9, 2017 http://ciajournals.org/ D ow nladed from LABORATORY INVESTIGATION-MYOCARDIAL BLOOD FLOW at the same level during a vasodilative stimulus as before. Changes in heart rate and/or systolic compressive forces also require consideration, since they may result in alterations in metabolic demand, diastolic period, and/or subendocardial impedance to flow. In the present studies a coronary pressure control system was used in paced heart-blocked dogs to minimize these problems.'4 The intent was to determine whether regional pressure reduction is an adequate stimulus for maximum vasodilation or whether reductions in flow can occur in the face of residual pharmacologic vasodilator reserve.