Understanding Putative Mechanisms of Coronary Flow Control
The coronary circulation is tightly regulated in order to ensure an adequate matching between myocardial oxygen delivery and metabolism. The precise modulation of coronary blood flow and myocardial oxygen supply-demand balance is demonstrated under many (patho)physiologic conditions such as exercise, alterations in perfusion pressure, and limitations in arterial oxygen content as observed with hemodilution or hypoxemia. Although this intricate coupling has been recognized for well over a century, our understanding of the underlying mechanisms remains rather limited. The purpose of this investigation is to delineate key pathways that contribute to the intricate interplay between the primary determinants of coronary blood flow in response to physiologic stimuli. Aim 1 studies were designed to examine potential mechanisms responsible for coronary vasodilation and the maintenance of myocardial oxygen delivery in response to moderate and severe reductions in hematocrit. Experiments provided evidence that ATP-sensitive (KATP) K+ channels, and not voltage-dependent (KV) K+ channels or nitric oxide, are required for progressive increases in coronary blood flow in response to acute isovolemic hemodilution in open-chest anesthetized domestic swine. Aim 2 studies were performed to examine coronary pressure-flow relations, which included autoregulatory capability (attenuation of changes in blood flow with respect to perfusion pressure) and zero flow pressure, before and during direct modulation of hematocrit, myocardial metabolism, and underlying vasomotor tone. Results from these studies suggest that coronary vascular tone is a major contributor to zero flow pressure, and that zero flow pressure is a chief contributor to the height (pressure) of the vascular waterfall present in the coronary circulation. Data from these studies provide novel insight into the intricate interaction of how specific alterations in oxygenation, metabolism and perfusion pressure modulate coronary vascular smooth muscle tone through distinct mechanisms.^
Johnathan D. Tune, Purdue University, Craig J. Goergen, Purdue University.
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