Impact of alpha-adrenergic coronary vasoconstriction on the transmural myocardial blood flow distribution during humoral and neuronal adrenergic activation.

Abstract

Increased heart rate and left ventricular pressure during humoral and neuronal adrenergic activation act to restrict blood flow preferentially in the subendocardium. The hypothesis was advanced that a-adrenergic coronary vasoconstriction preferentially in the subepicardium may counterbalance the enhanced extravascular compression in the subendocardium and serve to maintain blood flow transmurally uniform. In 40 anesthetized dogs, regional myocardial blood flow was determined with colored microspheres; wall function, with sonomicrometry. Humoral adrenergic activation (HAA) was induced by a combination of intravenous atropine, intravenous norepinephrine, and atrial pacing during baseline coronary vasomotor tone (group 1, n=6) and in the presence of maximal coronary vasodilation with intravenous dipyridamole (group 2, n=6). In an additional group, HAA was induced by intravenous norepinephrine in the presence of dipyridamole but without atropine and atrial pacing in order to increase end-diastolic left ventricular pressure (group 3, n=6). Measurements were performed at rest, during HAA, and during ongoing HAA with the intracoronary infusion of the a-antagonist phentolamine (Phen). At unchanged mean aortic pressure, Phen improved blood flow particularly to the inner layers as follows: from 1.42±0.40 (mean+SD) to 1.90±0.40 mL/(min g) (group 1, P<.05), from 4.99+2.31 to 5.53±2.56 mL/(min g) (group 2, P<.05), and from 6.01±1.41 to 6.29±1.27 mL/(min -g) (group 3, P<.05), associated with a decrease in outer layer blood flow in groups 2 and 3. In 16 additional dogs, 13-adrenoceptors were blocked by propranolol and muscarinic receptors by atropine. Neuronal adrenergic activation (NAA) was induced by cardiac sympathetic nerve stimulation (CSNS) during baseline coronary vasomotor tone (group 4, n=8) and in the presence of maximal vasodilation (group 5, n=8). Measurements were performed at rest, during a first CSNS, and 20 minutes later during a second CSNS+Phen. The reproducibility of two consecutive episodes of CSNS 20 minutes apart was demonstrated in a separate set of experiments (n=6). At matched mean aortic pressures, Phen improved blood flow to all myocardial layers in group 4, whereas in group 5, Phen induced a redistribution of myocardial blood flow toward subepicardial layers [from 4.44±0.96 to 4.81±0.83 mL/(min * g), P<.051 at the expense of inner layers.With the addition of Phen, there was no change in regional wall function in any group of dogs studied. Thus, during HAA, ar-adrenergic coronary vasoconstriction does not exert a beneficial effect on transmural blood flow distribution. During NAA, a beneficial effect of a-adrenergic coronary vasoconstriction becomes apparent only under conditions of maximal coronary vasodilation. (Circ Res. 1993;73:869-886

Neural Control of Coronary Blood Flow

“…This is consistent with the observation that sympathetic stimulation results in constriction of ∼100–250 µm diameter coronary microvessels and dilatation of arterioles smaller than ∼100 µm diameter [9]. During resting conditions α-adrenoceptor activation has little effect on transmural flow distribution, because there is an adequately long diastolic period to fill intramyocardial capacitance and there is ample vasodilator reserve in the subendocardium [2, 6, 40]. However, when tachycardia is combined with high coronary flow caused by adenosine infusion [27, 40], dipyridamole [2], or exercise [37] α-adrenoceptor activation has a favorable effect on transmural flow distribution.…”

“…During resting conditions α-adrenoceptor activation has little effect on transmural flow distribution, because there is an adequately long diastolic period to fill intramyocardial capacitance and there is ample vasodilator reserve in the subendocardium [2, 6, 40]. However, when tachycardia is combined with high coronary flow caused by adenosine infusion [27, 40], dipyridamole [2], or exercise [37] α-adrenoceptor activation has a favorable effect on transmural flow distribution. These observations may explain the well-documented paradoxical α-adrenoceptor-mediated coronary vasoconstriction during exercise.…”

“…The postulate is that coronary α-vasoconstriction has been adapted to adjust phasic coronary impedance to lessen wasteful to-and-fro flow during the cardiac cycle and thus preserve flow to the inner layer of the left ventricle when there is both a high heart rate and a high demand for flow. If both high flow and tachycardia are not present α-adrenoceptor activation has little effect on transmural flow distribution [2, 6, 40]. …”

α-Adrenergic Coronary Vasoconstriction and Myocardial Ischemia in Humans

“…Further progress in imaging technique (better spatial resolution in PET, echo contrast) will also permit study of ␣-adrenergic coronary constrictor influences on transmural blood flow distribution 66 in humans. Further progress is also expected from recent studies demonstrating a genetic determination of ␣-adrenergic coronary constriction.…”

Assesment of Autonomic Function in Slow Coronary Flow using Heart Rate Variability and Heart Rate Turbulence

“…The coronary vascular bed is wholly innervated by both the sympathetic and parasympathetic divisions of the autonomic nervous system [20,21]. Intact autonomic cardiac control appears to be an important protective factor in the pathophysiology of malignant arrhythmias and sudden cardiac death [12].…”