Experimental Biology and Medicine
Johnathan D. Tune, Keith Neu Richmond, Mark W. Gorman and Eric O. Feigl
Control of Coronary Blood Flow during Exercise
Experimental Biology and Medicine
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Control of Coronary Blood Flow during Exercise
JOHNATHAN D. TUNE,*,1KEITH NEU RICHMOND,† MARK W. GORMAN,‡ AND ERIC O. FEIGL‡
*Department of Integrative Physiology, University of North Texas Health Science Center, Fort
Worth, Texas 76107; †Division of Cardiovascular Biology, Shen Nippon Biomedical Laboratories,
Ltd., USA, Redmond, Washington 98052; and ‡Department of Physiology and Biophysics, University
of Washington School of Medicine, Seattle, Washington 98195
Under normal physiological conditions, coronary blood flow is
closely matched with the rate of myocardial oxygen consump-
tion. This matching of flow and metabolism is physiologically
important due to the limited oxygen extraction reserve of the
heart. Thus, when myocardial oxygen consumption is in-
creased, as during exercise, coronary vasodilation and in-
creased oxygen delivery are critical to preventing myocardial
underperfusion and ischemia. Exercise coronary vasodilation
is thought to be mediated primarily by the production of local
metabolic vasodilators released from cardiomyocytes second-
ary to an increase in myocardial oxygen consumption. How-
ever, despite various investigations into this mechanism, the
mediator(s) of metabolic coronary vasodilation remain un-
known. As will be seen in this review, the adenosine, K+
channel and nitric oxide hypotheses have been found to be
inadequate, either alone or in combination as multiple redun-
dant compensatory mechanisms. Prostaglandins and potas-
sium are also not important in steady-state coronary flow regu-
lation. Other factors such as ATP and endothelium-derived hy-
perpolarizing factors have been proposed as potential local
metabolic factors, but have not been examined during exercise
coronary vasodilation. In contrast, norepinephrine released
from sympathetic nerve endings mediates a feed-forward ?-
adrenoceptor coronary vasodilation that accounts for ∼25% of
coronary vasodilation observed during exercise. There is also a
feed-forward ?-adrenoceptor-mediated vasoconstriction that
helps maintain blood flow to the vulnerable subendocardium
when heart rate, myocardial contractility, and oxygen consump-
tion are elevated during exercise. Control of coronary blood
flow during pathophysiological conditions such as hyperten-
sion, diabetes mellitus, and heart failure is also addressed.
[Exp Biol Med Vol. 227(4):238–250, 2002]
Key words: adenosine; nitric oxide; K+
vasodilation; ?-adrenoceptor vasoconstriction
normal resting conditions, the heart extracts ∼75% of the
oxygen delivered by coronary blood flow, therefore the oxy-
gen extraction reserve is quite limited (1–3). Thus, myocar-
dial function is dependent on an adequate coronary blood
flow on a moment-to-moment basis.
Despite these seeming constraints at rest, the heart is
capable of increasing myocardial oxygen consumption
5-fold or more above resting values when there is tachycar-
dia, augmented contractility, and increased cardiac after-
load, as occurs during exercise (1–4). For this reason, ex-
ercise is frequently used to test the physiological mecha-
nisms that control coronary blood flow and thus oxygen
delivery to the heart.
The dominant determinant of coronary blood flow is
the rate of myocardial oxygen consumption, and the central
question in coronary physiology is how coronary flow is
coupled to myocardial oxygen consumption by a local meta-
bolic mechanism (1–4). As will be seen, the adenosine,
metabolic control of coronary blood flow during exercise
have been found inadequate individually and in combina-
tion. Therefore, the mechanism of local metabolic control of
coronary blood flow remains unknown, with no strong al-
ternative hypothesis available at this time.
In contrast to the negative results on identifying the
local metabolic vasodilator mechanism in the coronary cir-
culation, there have been positive findings on the neural
control of coronary blood flow during exercise. A feed-
forward ?-adrenoceptor-mediated coronary vasodilation
he anaerobic capacity of the mammalian heart is very
limited and if the oxygen supply is interrupted, the
affected myocardium quickly stops beating. During
ATPchannel, and nitric oxide hypotheses for the local
1To whom requests for reprint should be addressed at Department of Integrative
Physiology, University of North Texas Health Science Center, 3500 Camp Bowie
Boulevard, Fort Worth, TX 76107-2699. E-mail: email@example.com
Copyright © 2002 by the Society for Experimental Biology and Medicine
238CORONARY BLOOD FLOW DURING EXERCISE
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