Effect of stellate ganglion stimulation on myocardial blood flow, oxygen consumption, and cardiac efficiency during beta-adrenoceptor blockade

SUMMARY. We examined the late coronary vascular response to carotid chemoreceptor reflex activation in normal, conscious dogs instrumented for the measurement of right main and left circumflex coronary artery blood flows, arterial and right ventricular pressures, and arterial and coronary sinus blood gases and O 2 contents. With heart rate held constant by electrical stimulation, and with respiration controlled or allowed to vary spontaneously, carotid chemoreceptor reflex activation (induced by intracarotid nicotine) elicited a striking biphasic coronary vascular response characterized by an early dilation (previously described) and a late constriction. For example, with respiration controlled and with the autonomic nervous system intact, carotid chemoreceptor reflex activation resulted in a late increase in arterial pressure (19 ± 4%; P < 0.002), absolute reductions in right main (24 ± 4%; P < 0.002), and left circumflex (12 ± 2%; P < 0.004) coronary blood flows, and increases in right (62 ± 13%; P < 0.002) and left (26 ± 3%; P < 0.0001) coronary resistances. This carotid chemoreceptor reflex activation-induced late coronary constriction was also associated with a concomitant increase in myocardial oxygen extraction, i.e., arterial oxygen content remained constant, while coronary sinus oxygen content decreased (19 ± 6%; P < 0.04). Neither propranolol nor atropine had any significant effect on the magnitude of the right coronary constriction. However, both the absolute reduction in right coronary blood flow and increase in right coronary resistance were abolished by phentolamine. Furthermore, either total cardiac denervation or adrenalectomy significantly attenuated (P < 0.01) carotid chemoreceptor reflex activation-induced reductions in right coronary blood flow and increase in right coronary resistance. We conclude that, with autonomic nervous system activity intact, carotid chemoreceptor reflex activation can elicit an absolute reflexly mediated reduction in coronary blood flow in the normal, conscious dog, despite an increase in arterial pressure. The mechanism of this vasoconstriction involves a-adrenergic receptor stimulation mediated by both cardiac sympathetic nerves and circulating catecholamines. {Circ Res 54: 96-106, 1984) THERE NOW exists a relatively large body of experimental evidence which supports the concept that sympathetic activation can result in a-adrenergic coronary vasoconstriction. This concept is based primarily on experiments in which sympathetic activation has resulted in increases in arterial pressure which have been greater than concomitant increases in coronary blood flow, with a consequent increase in coronary resistance. It is somewhat surprising that despite recent interest in the role of coronary vasoconstriction in the pathogenesis of coronary artery vasospasm (Hillis and Braunwald, 1978;Maseri et al., 1978), there is little compelling evidence that aadrenergic vasoconstriction can mediate an absolute reduction in coronary blood flow in the presence of an intact autonomic n...

Section: Discussionmentioning

confidence: 99%

Alpha-adrenergic-mediated reduction in coronary blood flow secondary to carotid chemoreceptor reflex activation in conscious dogs.

Murray

Lavallée

Vatner

1984

“…14 1(i When /3-receptor blockade is used to blunt changes in myocardial metabolism, sympathetic activation produces coronary vasoconstriction and decreased coronary venous oxygen levels. 8 ' "• 27 The coronary vasoconstriction and depressed venous oxygen tension due to sympathetic nerve stimulation observed in a {I-receptor blocked preparation are prevented by a-receptor blockade. 17 In the absence of /3-receptor blockade, electrical stimulation of the stellate ganglion has been reported to produce a lesser coronary vasodilation than that resulting when coronary sinus oxygen levels are reduced to similar levels by systemic hypoxia.…”

Section: Neural Controlmentioning

confidence: 99%

Competition between sympathetic vasoconstriction and metabolic vasodilation in the canine coronary circulation.

Mohrman¹,

Feigl²

1978

248

Before a-receptor blockade, either intracoronary norepinephrine infusion or reflex sympathetic activation from the carotid sinus resulted in an increase of only 0.85 ml/100 g mirr' in oxygen delivery for each increase of 1 ml/100 g min" 1 in cardiac oxygen consumption. Under these circumstances, myocardial oxygen extraction increased and coronary venous oxygen content fell. After a-receptor blockade, either intracoronary norepinephrine infusion or a carotid sinus reflex resulted in an increase of 1.23 ml/100 g min ' in oxygen delivery for each increase of 1 ml/100 g min' 1 in cardiac oxygen consumption. Myocardial oxygen extraction and coronary venous oxygen content changed only slightly after a-receptor blockade. The greater coronary vasodilation and lesser change in cardiac oxygen extraction after a-receptor blockade were significantly different (P < 0.001) from the values before blockade. It is concluded that the coronary a-receptor constrictor mechanism competes with metabolic vasodilation during sympathetic activation even when there are large increases in myocardial metabolism. The net effect of the a-receptor constrictor influence is to restrict the metabolically related flow increase by about 30%, thus increasing oxygen extraction and decreasing coronary venous oxygen content.IT HAS LONG been known that stimulation of the sympathetic innervation of the heart results in tachycardia and augmented contractility, accompanied by increased myocardial oxygen consumption, increased coronary blood flow, and decreased coronary sinus oxygen content. A previous study in this laboratory demonstrated that sympathetic a-receptor coronary vasoconstriction is capable of competing with local metabolic control and lowering coronary sinus oxygen tension after adrenergic /3-receptor blockade. 17 In that study the positive inotropic and chron-

“…effect of caffeine, 12 are most easily understood as indicating that mechanical activation in this tissue is primarily mediated by transsarcolemmal calcium movements. Niedergerke et al 13 have recently summarized other items of experimental support for this view, as well as results indicating the presence of a mechanism which "acts in the cell interior, involving a calcium-dependent process of an as yet unknown nature."…”

Section: Staircase Excitation and Extracellular Lons/chesnais Et Almentioning

confidence: 99%

Segmental alpha-receptor-mediated vasoconstriction in the canine coronary circulation.

Kelley¹,

Feigl²

1978

118

SUMMARY Recent studies from this laboratory have indicated that sympathetic a-receptor-mediated coronary vasoconstriction can compete with local metabolic vasodilation to reduce the oxygen supply to the myocardium. In vitro studies from other laboratories on isolated coronary vessel strips suggest that large epicardial vessels are the dominant site of adrenergic a-receptor activity. In this study we used anesthetized, open-chest dogs to test the hypothesis that a-receptor-mediated vasoconstriction occurs predominantly in epicardial vessels, which are partially removed from the metabolic milieu in the myocardium. Adrenergic jS-receptor blockade was achieved by propranolol (3 mg/kg, iv). The circumflex coronary artery was pump-perfused at constant pressure to minimize passive changes in large vessel resistance. Pressure was measured at the tip of the perfusion cannula sealed in the circumflex artery, and in an apical branch of the circumflex artery. Large vessel resistance was calculated as the pressure gradient along the vessel segment divided by the coronary flow. Intracoronary injections of nitrogly cerin were used as an independent measure of the vasomotor responsiveness of the large vessel segment. Adrenergic a-receptor activation was produced by intracoronary bolus injections of norepinephrine and by electrical stimulation of the left stellate ganglion. Alpha-receptor stimulation caused an increase in total coronary vascular resistance; however, the relative increase in the resistance of the large vessel was only about 60% of that seen for the entire coronary bed. These data suggest that, contrary to the proposed hypothesis, adrenergic a-receptor-mediated vasoconstriction in the large coronary vessels is not proportionally greater than that observed in the total coronary vascular bed.DIRECT sympathetic coronary vasoconstriction is well recognized 1 " 15 and is of the a-receptor type. 45 ' 10 ' 16 Zuberbuhler and Bohr, 17 using in vitro isolated coronary vessel strips, found that adrenergic a-receptor-stimulated contractions were observed more often in strips from large (1.5-2.4 mm in diameter) than from small (0.25-0.50 mm) arteries. This finding has been confirmed in other in vitro studies. 18 " 20 Recent studies from this laboratory have indicated that sympathetic a-receptorinduced coronary vasoconstriction is capable of limiting oxygen delivery to the heart and decreasing myocardial oxygen tension, thus competing with local metabolic coronary vasodilation. 21 ' 22 These findings suggested the hypothesis that the principal site of a-receptor coronary vasoconstriction might be the large epicardial coronary vessels; since the large upstream epicardial vessels presumably are somewhat removed from the metabolic milieu surrounding small vessels within the myocardium, this hypothesis could explain sympathetic coronary vasoconstriction overriding local metabolic vasodilation. The purpose of the present study was to test the hypothesis that a-receptor vasoconstriction occurs predominantly in epicardial vessels by...