Review article
Mechanisms of metabolic coronary flow regulation

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Abstract

Coronary blood flow is tightly adjusted to the oxygen requirements of the myocardium. The underlying control mechanisms keep coronary venous pO2 at a rather constant level around 20 mm Hg under a variety of physiological conditions. Because coronary flow may increase more than 5-fold during exercise without any signs of under- or overperfusion, coronary flow must be controlled, at least in part, in a feed forward manner. Likely metabolic factors contributing to feed forward control are carbon dioxide and reactive oxygen species. Adaptation of coronary flow to exercise under physiological conditions involves in addition to metabolic control feed forward neuronal and endothelium-dependent control. Under pathological conditions, e.g. vessel stenosis or anemia, or specific environmental conditions, e.g. high altitude exposure, cardiac oxygenation may become critical, especially if oxygen demand is increased during physical exercise. Under such conditions the fall of coronary pO2 may directly result in opening of oxygen sensitive potassium or closure of calcium channels. Furthermore the fall of pO2 results in the production of vasoactive metabolites, e.g. adenosine, nitric oxide or prostaglandins, and in proton accumulation. All of these adaptations support a reduction of coronary vessel resistance. This article is part of a Special Issue entitled “Coronoray Blood Flow”.

Highlights

► Physiological coronary flow adaptation avoids impaired myocardial oxygenation. ► Production of CO2 and ROS reflects myocardial oxygen consumption. ► Under pathological conditions further vasoactive metabolites are produced. ► These include adenosine, nitric oxide, prostaglandins and protons. ► Flow control mechanisms merge on the level of potassium channels.

Introduction

Coronary blood flow is intimately coupled to myocardial oxygen consumption. The average myocardial oxygen extraction is known to be 60–70% under resting physiological conditions which results in a coronary venous pO2 around 20 mm Hg. While coronary venous pO2 is maintained constant even during strenuous physical exercise, there exists a close link between local myocardial (aerobic) energy metabolism and blood flow [1], [2]. Also with respect to the given broad spatial heterogeneity of myocardial blood flow under baseline physiological conditions [3], [4], [5], [6] there is no indication of disturbed local tissue oxygenation neither acutely nor chronically [7], [8], [9], [10], [11], [12], [13], [14]. The local functional coupling of blood flow and myocardial metabolism is achieved by feed forward and feed back control mechanisms, and it is believed that metabolic flow regulation is a key component [15]. This review summarizes the current evidence for different modes of coronary metabolic regulation.

Section snippets

Flow control in proportion to myocardial oxygen consumption

A typical feature of blood flow adaptation to exercise is an only small or even absent change of coronary venous pO2 [2]. Such a feature may be explained by feed forward control of coronary blood flow. Metabolites which control myocardial blood flow in a feed forward manner must be produced at a rate in proportion to oxidative metabolism. Examples for such metabolites are carbon dioxide, which is generated in decarboxylation reactions of the citric acid cycle, and reactive oxygen species, which

Flow control during tissue hypoxia

A disturbance of myocardial oxygenation occurs, if coronary flow and thereby oxygen supply does not meet the requirement for oxygen by the myocardium. Thus, impairment of myocardial oxygenation is a hallmark of myocardial ischemia. Whether myocardial oxygenation may become impaired under physiological conditions at all, is not entirely clear. However, if it occurs then it is likely related to coronary blood vessels which conduct an only small fraction of the bulk flow. Under conditions of

Effector mechanisms

Coronary vasodilation results when the intracellular calcium concentration of vascular smooth muscle decreases or the Ca2+-sensitivity of the contractile machinery declines. Transsarcolemmal calcium influx may be prevented after hyperpolarization of the membrane potential. In vascular smooth muscle membrane hyperpolarization typically occurs in response to potassium channel activation. Acidosis was shown to increase the open probability of KATP-channels in the relevant pH range from 7.4 to 6.5

Summary

Our goal in this review was to bring to light some recent concepts in the metabolic controls in the coronary circulation as summarized in Fig. 5. Although the literature is replete with studies on connecting flow to metabolism in the heart, we have to mention that to date we have more hypotheses than accepted fact. The classical scheme for adenosine linking metabolism to flow via a negative feedback pathway is likely incorrect. And should there be any editors of text books or contributors to

Disclosure statement

None declared.

Acknowledgment

The skilful secretarial assistance of Mrs. Ursula Raabe is greatly appreciated.

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