Review article
Regulation of coronary resistance vessel tone in response to exercise

https://doi.org/10.1016/j.yjmcc.2011.10.007Get rights and content

Abstract

Exercise is a primary stimulus for increased myocardial oxygen demand. The ~ 6-fold increase in oxygen demand of the left ventricle during heavy exercise is met principally by augmenting coronary blood flow (~ 5-fold), as hemoglobin concentration and oxygen extraction (which is already ~ 70% at rest) increase only modestly in most species. As a result, coronary blood flow is tightly coupled to myocardial oxygen consumption over a wide range of physical activity. This tight coupling has been proposed to depend on periarteriolar oxygen tension, signals released from cardiomyocytes and the endothelium as well as neurohumoral influences, but the contribution of each of these regulatory pathways, and their interactions, to exercise hyperemia in the heart remain incompletely understood. In humans, nitric oxide, adenosine and KATP channels each appear to contribute to resting coronary resistance vessel tone, but evidence for a critical contribution to exercise hyperemia is lacking. In dogs KATP-channel activation together with adenosine and nitric oxide contribute to exercise hyperemia in a non-linear redundant fashion. In contrast, in swine nitric oxide, adenosine and KATP channels contribute to resting coronary resistance vessel tone control in a linear additive manner, but do not appear to be mandatory for exercise hyperemia. Rather, exercise hyperemia in swine appears to involve β-adrenergic activation in conjunction with exercise-induced blunting of an endothelin-mediated vasoconstrictor influence. In view of these remarkable species differences in coronary vasomotor control during exercise, future studies are required to determine the system of vasodilator components that mediate exercise hyperemia in humans. This article is part of a Special Issue entitled “Coronary Blood Flow”.

Highlights

► Mechanisms of exercise hyperemia in the heart remain incompletely understood. ► Mechanisms of exercise hyperemia appear highly species dependent. ► Hyperemia in dogs involves adenosine, nitric oxide, and KATP channel activation. ► Hyperemia in swine involves β-adrenergic activation and loss of endothelin influence. ► The mechanisms of exercise hyperemia in the human heart await further elucidation.

Introduction

Cardiac function is critically dependent on adequate oxygenation of the myocardium since oxidative phosphorylation is the most important source of energy production, with less than 5% of ATP production resulting from glycolytic metabolism [1]. As the heart pumps continuously throughout life, at a rate of at least 60 beats per minute, myocardial energy requirements are high. The heart has therefore been equipped with a very efficient system of oxygen utilization: 60–80% of the arterially delivered oxygen is actually utilized for energy production [2], [3] which is achievable due to the high capillary density of 3000–4000 per mm2 in the myocardium [4].

In view of the high resting levels of myocardial oxygen extraction, increasing oxygen extraction during exercise [5], [6], [7], [8], [9], [10] is insufficient to meet the increased oxygen demand produced by exercise (increasing up to 6-fold during maximal exercise). Hence, the increased myocardial oxygen demands during exercise are met principally by augmenting oxygen delivery, and hence by increasing coronary blood flow (CBF). Moreover, in dogs [11], [12], horses [13], [14] and sheep [15], oxygen delivery during exercise is further facilitated by increases in hemoglobin of up to 30–50%, while hemoglobin concentrations increase by only 10–15% in swine [16], [17], [18] and in humans [19], [20]. The increase in CBF results from a combination of coronary vasodilation, with a decrease of coronary vascular resistance during heavy exercise to 20–30% of the resting level, and a 20–40% increase in mean arterial pressure [7], [8], [9], [10], [11], [14], [21], [22], [23]. Despite intense research efforts over the past decades, the pathways involved in exercise-induced coronary vasodilation remain incompletely understood. In this review, we provide an update of previous reviews on regulation of CBF during exercise [2], [3], [24], [25], [26], [27]. Although the majority of studies reviewed in this article have been performed in animal species, we have included data from human studies where available which, unless otherwise stated, were performed in healthy volunteers.

Section snippets

Coronary blood flow

Dynamic exercise increases CBF in proportion to the increase in heart rate, with peak CBF values during maximal exercise typically 3 to 5 times the resting level [9], [14], [28], [29], [30], [31], [32]. The strong correlation between coronary flow and heart rate occurs because heart rate is a common multiplier for the other determinants of myocardial oxygen demand (contractility and cardiac work), which are computed per beat. Regression analysis of published left ventricular myocardial blood

Myocardial oxygen extraction

In many species, the increased oxygen demand during exercise is met in part by an increased myocardial oxygen extraction, with widening of the arterio-venous O2 difference and a decrease in coronary venous oxygen content [9], [10], [11], [22], [33], [68], [71], [91], [92], [93]. Thus, in dogs [9], [33] and horses [10], myocardial oxygen extraction increases progressively with increasing exercise intensity. In humans, myocardial oxygen extraction increases during heavy exercise [22], [68], [71],

Regulation of coronary resistance vessel tone during exercise

During exercise the increase in aortic pressure only slightly exceeds the increase in effective back pressure, so that the effective perfusion pressure increases by no more than 20–30% [10], [104]. Consequently, the exercise-induced 4 to 6-fold increase in CBF is mediated principally by a decrease in coronary vascular resistance. Indeed, maximal exercise is associated with decreases in calculated coronary vascular resistance to 20–30% of basal resting values in dogs [8], horses [14], [28],

Disclosures

None.

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