Reduced regional myocardial perfusion in the presence of pharmacologic vasodilator reserve.

Abstract

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 -'g-when 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.

Residual coronary reserve despite decreased resting blood flow in patients with critical coronary lesions. A study by technetium-99m human albumin microsphere myocardial scintigraphy.

“…Assuming that the descending aorta does not change in (9) diameter in the few minutes throughout the study, and maintaining the same geometry between the patient and the detector, the changes in radioactivity detected in a fixed region of interest can be considered linearly correlated with the (10) changes in the radioactivity concentration by a factor K that remains constant throughout the study. 2) The second problem arises from the passage of the tracer first through the catheter then in the aorta under the same region of interest.…”

Paradoxical coronary microcirculatory constriction during ischemia: a synergic function for nitric oxide and endothelin

“…Nevertheless, the concept of autoregulation has been extended to predict a maximal dilation of coronary microvessels in the myocardium being rendered ischemic by a severe stenosis. This assumption is still largely accepted, despite a number of experimental (6,12,15,16,21) and clinical (24,30,32,34) studies documenting submaximal vasodilation or a full-fledged vasoconstriction in response to increased myocardial oxygen demand while blood flow is limited by coronary obstruction. Our study proves that a vasoconstrictive response to hypotension occurs with the heart from healthy animals, hence excluding atherosclerotic impairment of vascular function as a prerequisite.…”

“…Because of the concomitant coronary artery disease, it has been hypothesized that this paradoxical response results from reduced nitric oxide (NO) bioavailability (20,25) and/or increased endothelin (ET) release (20), because both such events are characteristic of coronary atherosclerosis. However, microcirculatory vasoconstriction, or submaximal vasodilation, has also been observed in the normal animal during severe ischemia or coronary hypotension (6,12,15,21). Relevant to the latter observation is the generation during ischemia of reactive oxygen species (ROS) promoting the conversion of NO to peroxynitrite with the attendant activation of the ET-1 system.…”

Effects of adenosine on human coronary arterial circulation.

“…Although the importance of obtaining absolutely maximal (as opposed to near-maximal) coronary vasodilation may be insignificant because epicardial coronary stenoses first cause vasodilation of the subendocardium (the layer most sensitive to the vasodilator properties of adenosine), further clinical studies will be needed to define the comparative sensitivity of 20lfl scintigraphy obtained using adenosine or dipyridamole. 35,36 The second clinical use of adenosine is in measuring coronary flow reserve in the catheterization laboratory. Intracoronary papaverine, the agent most commonly used to measure flow reserve, cannot be given as a continuous infusion (making difficult its use with measurement techniques with poor temporal resolution such as digital subtraction angiographic methods) and can cause ventricular tachycardia.7 Intracoronary adenosine (bolus or infusion) may be more advantageous than papaverine because it can be given as a continuous infusion without resulting in systemic accumulation, it has no important effects on the electrocardiogram at the doses tested, and it has a short half-life that reduces the potential sequelae of any toxicity (for example, heart block).…”