Regulation of Coronary Blood Flow

Abstract

The heart is uniquely responsible for providing its own blood supply through the coronary circulation. Regulation of coronary blood flow is quite complex and, after over 100 years of dedicated research, is understood to be dictated through multiple mechanisms that include extravascular compressive forces (tissue pressure), coronary perfusion pressure, myogenic, local metabolic, endothelial as well as neural and hormonal influences. While each of these determinants can have profound influence over myocardial perfusion, largely through effects on end-effector ion channels, these mechanisms collectively modulate coronary vascular resistance and act to ensure that the myocardial requirements for oxygen and substrates are adequately provided by the coronary circulation. The purpose of this series of Comprehensive Physiology is to highlight current knowledge regarding the physiologic regulation of coronary blood flow, with emphasis on functional anatomy and the interplay between the physical and biological determinants of myocardial oxygen delivery.

Regulation of myocardial oxygen delivery in response to graded reductions in hematocrit: role of K+ channels

“…It is well established that reductions in hematocrit lead to marked hemodynamic responses including increases in cardiac output, heart rate, contractility, and MVO 2 [8, 30, 37, 64], all of which are important determinants of coronary blood flow [25]. In the present study, we noted significant differences in the coronary response to hemodilution in swine that received volume replacement with saline vs Hespan.…”

“…More specifically, how changes in hematocrit are sensed is simply not understood. Classically, changes in myocardial tissue PO 2 , which are indexed by changes in coronary venous PO 2 , are proposed to invoke the production of vasodilator factors that act to increase coronary blood flow and restore tissue PO 2 to normal levels via negative feedback loop [25]. However, the consistency of coronary venous PO 2 (myocardial oxygen extraction) as hematocrit is lowered to < 10% (Figure 3) has been found in rats [69], dogs [7, 12, 37, 61], pigs [64], baboons [68], and humans [24] and directly argues against this traditional paradigm.…”

“…K + channels dominate membrane conductance of coronary vascular smooth muscle and serve as important end-effector mechanisms of endogenous and exogenous vasodilator compounds [17, 25]. In particular, K V channels have been shown to contribute to the control of coronary blood flow at rest, during increases in MVO 2 , and following a brief coronary artery occlusion [2, 16, 26, 27, 49, 53].…”

“…Data from this study are the first to demonstrate that the inhibition of K ATP channels with glibenclamide markedly diminishes increases in coronary blood flow (Figure 6A) and myocardial oxygen delivery (Figure 6B) in response to progressive reductions in hematocrit. It is important to point out that glibenclamide significantly decreased MVO 2 by ~45-50% at all levels of hematocrit (Table 2) and that such reductions in MVO 2 could result in decreases in coronary blood flow, possibly via effects on mitochondrial K ATP channels [25]. However, we propose that this is likely not the case as the progressive reduction of the coronary blood flow response to decreases in hematocrit in glibenclamide treated swine (Figure 6A) does not correspond with augmented decreases in MVO 2 (Table 2).…”

“…However, whether nitric oxide contributes to the coronary dilator response as hematocrit is reduced below 20% has not been determined. Alternatively, end-effector K + channels in vascular smooth muscle are regulated by a variety of influences including endogenous endothelial and metabolic factors [25], cellular energy status (ATP/ADP ratio) [13, 25, 48], redox-dependent signaling [53], and the overall degree of oxygenation [21, 28]. Yet, whether these channels contribute to the balance between myocardial oxygen delivery and metabolism in response to progressive hemodilution has not been determined.…”