Acute Cardiac Denervation Research Articles

Arterial baroreceptors control plasma vasopressin responses to graded hypotension in conscious dogs.

We studied the role of cardiac and arterial baroreceptors in the reflex control of arginine vasopressin (AVP) and renin secretion during graded hypotension in conscious dogs. The dogs were prepared with Silastic cuffs on the thoracic inferior vena cava and catheters in the pericardial space. Each experiment consisted of a control period followed by four periods of inferior vena caval constriction, during which mean arterial pressure (MAP) was reduced in increments of approximately 10 mmHg. The hormonal responses were measured in five dogs under four treatment conditions: 1) intact, 2) acute cardiac denervation (CD) by intrapericardial infusion of procaine, 3) after sinoaortic denervation (SAD), and 4) during combined SAD+CD. The individual slopes relating MAP to plasma AVP and plasma renin activity (PRA) were used to compare the treatment effects using a 2 x 2 factorial analysis. There was a significant (P < 0.01) effect of SAD on the slope relating plasma AVP to MAP but no effect of CD and no SAD x CD interaction. In contrast, the slope relating PRA and MAP was increased (P < 0.05) by SAD but was not affected by CD. These results support the hypothesis that stimulation of AVP secretion in response to graded hypotension is primarily driven by unloading arterial baroreceptors in the dog.

Arterial baroreceptors control blood pressure and vasopressin responses to hemorrhage in conscious dogs

The goal of this study was to determine the role of arterial baroreceptors in the reflex control of arginine vasopressin (AVP), renin, and cortisol secretion in response to a 30-ml/kg hemorrhage in conscious dogs. The hormonal responses were measured in six dogs under four treatment conditions: 1) intact, 2) acute cardiac denervation (CD) by intrapericardial infusion of procaine, 3) after sinoaortic denervation (SAD), and 4) during combined SAD + CD. In the intact condition, mean arterial pressure (MAP) was maintained at control levels until blood loss reached 20 ml/kg and the absolute magnitude of the fall at 30 ml/kg was 35 +/- 10 mmHg. Similar responses were obtained during acute CD. In contrast, MAP fell earlier (at 5 ml/kg, P < 0.05) and to much lower levels in both the SAD and SAD + CD conditions. The individual slopes relating systolic pressure to plasma AVP, renin activity (PRA), and cortisol were used to compare the treatment effects using a 2 x 2 factorial analysis. There was a significant (P < 0.01) effect of SAD on the slope relating AVP to systolic pressure but no effect of CD and no SAD x CD interaction. In contrast, there was no effect of either SAD or CD on the relationship between PRA or plasma cortisol and systolic pressure. These results indicate that maintenance of blood pressure and the normal pattern of AVP secretion during hemorrhage depend on intact arterial baroreceptor reflexes.

Bradycardia produced by pyridostigmine and physostigmine.

The bradycardia produced by pyridostigmine and physostigmine in an animal model of acute cardiac denervation was examined according to its relation to cholinesterase inhibition and sensitivity to block by cholinergic receptor antagonists. Cats were anaesthetised, vagotomised and propranolol-treated. Heart rate was continuously recorded. Erythrocyte cholinesterase activity of arterial blood was measured using a radiometric technique. Nicotinic and muscarinic M1 receptors were blocked with hexamethonium and pirenzepine, respectively. M2 receptors were blocked with gallamine, pancuronium and AFDX-116. With pyridostigmine and physostigmine the dose-response relationship for the decrease in heart rate (ED50 1.05 +/- 0.25 and 0.198 +/- 0.03 mg.kg-1, respectively) was shifted to the right of that for the inhibition of cholinesterase activity (ED50 0.094 +/- 0.03 and 0.032 +/- 0.01 mg.kg-1, respectively). The decrease in cholinesterase activity reached a plateau at a cumulative dose of 0.56 +/- 0.08 and 0.32 +/- 0.08 mg.kg-1, respectively. In contrast, there did not appear to be a plateau in the bradycardic effect. The bradycardia produced by pyridostigmine and physostigmine was blocked by hexamethonium (ED50 10 +/- 1.3 and 15.3 +/- 2.4 mg.kg-1, respectively), pirenzepine (ED50 68 +/- 16 and 138 +/- 32 micrograms.kg-1, respectively), gallamine (56 +/- 11 and 67 +/- 17 micrograms.kg-1, respectively), pancuronium (32 +/- 10 and 30 +/- 4 micrograms.kg-1, respectively), and AFDX-116 (31 +/- 4 and 28 +/- 4 micrograms.kg-1, respectively). The bradycardia produced by reversible anticholinesterase drugs containing a carbamyl group is not clearly related to the degree of cholinesterase activity, and has a low sensitivity to nicotinic and muscarinic M1 and a high sensitivity to muscarinic M2 receptor antagonists.

Heart rate changes in cardiac transplant patients and in the denervated cat heart after edrophonium.

The effect of edrophonium on heart rate in cardiac transplant patients and in an animal model of acute cardiac denervation were studied, to evaluate the functional state of the peripheral parasympathetic pathway following cardiac denervation. Edrophonium was studied in patients with normally innervated hearts (controls) and in cardiac transplants. Edrophonium was also studied in vagotomized, beta-blocked cats. In Group I animals, the vagus nerve was not stimulated. In Groups 2 & 3 the right vagus nerve was electrically stimulated to produce approximately 20% and 40% reductions in baseline heart rate, respectively. Maximum heart rate reduction in transplants (7.3 +/- 0.8 beats.min-1 with 0.6 +/- 0.08 mg.kg-1) was less than in controls (13.3 +/- 1.6 beats.min-1 with 0.4 + 0.05 mg.kg-1, P < 0.01). In Group I animals heart rate decreased maximally by 20.9 +/- 2.5 beats.min-1 with 9.0 +/- 1.9 mg.kg-1. In Groups 2 and 3, with doses < 1.5 mg.kg-1, reductions in heart rate were greater than in Group I and maximum reductions were obtained with lower doses (Group 2: maximum reduction by 20.3 +/- 2.8 beats.min-1 with 1.3 +/- 0.1 mg.kg-1; Group 3:22.6 +/- 4.0 beats.min-1 with 0.8 +/- 0.2 mg.kg-1, P < 0.001). Doses > 1.5 mg.kg-1 in Groups 2 and 3 produced increases in heart rate. Edrophonium produced bradycardia in cardiac transplants suggesting spontaneous release of acetylcholine from parasympathetic postganglionic neurons in the transplanted heart. The magnitude of the bradycardia was less in transplant than in control patients. Findings from animal studies suggest that the reduction in transplants can be attributed to diminution or absence of tonic cardiac parasympathetic drive. At high doses, edrophonium may interfere with parasympathetic neuron activation.

Relative roles of cardiac and arterial baroreceptors in vasopressin regulation during hemorrhage in conscious dogs.

To determine the relative roles of cardiac and sinoaortic baroreceptors in mediation of arginine vasopressin (AVP) release, hemorrhage was performed in five groups of conscious splenectomized dogs: 1) all nerves intact; 2) either chronic surgical or acute pharmacological (intrapericardial lidocaine) cardiac denervation (CD); 3) chronic sinoarotic denervation (SAD); 4) combined chronic sinoartic denervation plus either chronic or acute cardiac denervation (SAD + CD); and 5) all nerves intact, but with ganglionic blockade. Hemorrhage (0.5 ml/min/kg) reduced mean arterial pressure similarly in the intact and CD groups. Decreases in mean arterial pressure were augmented in SAD, SAD + CD, and ganglion-blocked groups compared with responses in intact and CD groups. There were no differences in responses of plasma AVP to hemorrhage in the intact and CD groups, but the AVP response was significantly blunted in the SAD + CD group as compared with SAD alone. When compared during the early stage of hemorrhage, at the same reduction in mean arterial pressure, the rise in AVP was greater in the ganglion-blocked group than in the SAD + CD group, but was less than in the intact group. With a protocol to reduce mean arterial pressure by 20 mm Hg over the same period (42 +/- 0.6 minutes) in four of the groups, the blood volume required to reduce mean arterial pressure by 20 mm Hg was similar in the intact (20 +/- 1 ml/kg) and CD (21 +/- 1 ml/kg) groups, but was less in the SAD (12 +/- 1 ml/kg) and SAD + CD (12 +/- 1 ml/kg) groups. Again, similar increases were observed in AVP between the intact (50 +/- 9 pg/ml) and CD (51 +/- 9 pg/ml) groups, whereas increases in AVP were diminished in the SAD (11 +/- 3 pg/ml) and SAD + CD (7 +/- 2 pg/ml) groups. In the presence of an AVP antagonist, decreases in mean arterial pressure and increases in total peripheral resistance with hemorrhage were affected similarly in both the intact and CD groups, whereas hemodynamic impairment by AVP blockade was less marked in the SAD and SAD + CD groups. These results indicate that cardiac receptors are not the major regulators of AVP release during progressive hemorrhage in conscious dogs. However, when the complicating influences of sinoaortic reflexes were eliminated, a modest role for cardiac receptors was uncovered.

Relative roles of cardiac receptors and arterial baroreceptors during hemorrhage in conscious dogs.

To determine the relative roles of cardiac receptors and arterial baroreceptors during blood loss, the effects of acute hemorrhage on measurements of mean arterial pressure, cardiac output, stroke volume, total peripheral resistance, and heart rate were examined in chronically instrumented, conscious dogs with all nerves intact (n = 15) and following either cardiac denervation (CD, n = 14), sinoaortic denervation alone (SAD, n = 11), or combined sinoaortic denervation plus cardiac denervation (SAD + CD, n = 8). Hemorrhage at a constant rate (0.5 ml/kg/min) was continued until mean arterial pressure fell to 40 mm Hg or 30 ml/kg of blood was withdrawn. Hemorrhage (20 ml/kg) decreased mean arterial pressure similarly in the intact group (-15 +/- 3.3 mm Hg) and CD group (-17 +/- 3.2 mm Hg), but to a greater extent in the SAD (-53 +/- 3.4 mm Hg) and SAD + CD (-49 +/- 2.9 mm Hg) groups. Total peripheral resistance increased similarly in the intact (20.4 +/- 3.0 mm Hg/l/min) and CD (22.4 +/- 2.4 mm Hg/l/min) groups, but did not increase in SAD and SAD + CD groups. Acute cardiac denervation induced with intrapericardial lidocaine in either the intact or SAD groups resulted in similar responses of mean arterial pressure to hemorrhage as those observed in the chronic CD and chronic SAD + CD groups, respectively. Thus, dogs with cardiac denervation withstand hemorrhage and increase total peripheral resistance to a similar extent as intact dogs.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of acute and chronic cardiac denervation on osmotic release of vasotocin in chickens.

Hypo- and hyperosmotic NaCl were infused intravenously to examine osmotic release of arginine vasotocin (AVT) in anesthetized, acutely cardiac-denervated chickens and in conscious, chronically denervated birds. Mean arterial blood pressure was consistently higher in denervated compared to sham-operated chickens but heart rates were similar in experimental and control groups. Plasma AVT concentrations (pAVT) were significantly higher than controls in acutely, but not chronically, denervated chickens. The slope of the regression line relating pAVT to plasma sodium concentration was higher in denervated birds indicating that removal of cardiac receptor activity increases the osmotic sensitivity of the AVT system. The results suggest that cardiac end-net receptor activity may participate in the regulation of blood pressure and can modulate the release of antidiuretic hormone in the chicken.

Protective effect of chronic versus acute cardiac denervation on contractile force during coronary occlusion

The effects of acute coronary artery (CA) occlusion on myocardial contractile force were studied in mongrel dogs with (1) chronically denervated hearts (n = 10), (2) acutely denervated hearts (n = 5), and (3) normally innervated hearts (n = 6). Contractile force was measured in ischemic and nonischemic areas using Walton-Brodie strain gauge arches sutured to the epicardium. Coronary occlusion was accomplished by ligating several small branches of the left anterior descending and the circumflex arteries supplying the apical region on the left ventricle. Following occlusion, contractile force in the ischemic area decreased by 66.8% in the control group, by 73.6% in the acutely denervated group, but only by 21.6% (P less than 0.001) in the chronically denervated group. These results demonstrate that chronic cardiac denervation protects from the severe loss of contractile force in the ischemic area. This salutary effect is not seen with acute cardiac denervation.

Inotropic and chronotropic responses of the in vivo denervated dog myocardium to dobutamine.

The inotropic and chronotropic responses to dobutamine (DBA) and isoprenaline (5ISO) were examined in eight chloralose anaesthetised dogs. Following acute cardiac denervation, heart rate (HR) and contractility (dP/dtmax), measured at a fixed paced atrial rate, were recorded during intravenous infusion of incremental doses of DBA and ISO. Both DBA and ISO elicited increases in HR and dP/dtmax. The increases in dP/dtmax for a one beat per minute increase in HR was 102.0 +/- 10.6 mm Hg/s (1 mm Hg (0 degree C) = 133.322 Pa), during DBA infusion, and 61.5 +/- 8.4 mm Hg/s during ISO infusion. It appeared that the relatively greater inotropic effect of DBA in comparison with ISO was the result of an augmentation of its inotropic activity. DBA infusion was accompanied by a significant increase in mean aortic pressure at all doses examined. An increase in afterload may account for part of the increased inotropic responses to DBA.

Effects of isoproterenol on contractile function of the ischemic and anoxic heart.

ARTICLESEffects of isoproterenol on contractile function of the ischemic and anoxic heartS Davidson, PR Maroko, and E BraunwaldS Davidson, PR Maroko, and E BraunwaldPublished Online:01 Aug 1974https://doi.org/10.1152/ajplegacy.1974.227.2.439MoreSectionsPDF (1 MB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformation Cited ByProbenecid: Novel use as a non-injurious positive inotrope acting via cardiac TRPV2 stimulationJournal of Molecular and Cellular Cardiology, Vol. 53, No. 1Neuroadrenergic activation and response to dobutamine in congestive heart failure secondary to idiopathic dilated cardiomyopathyThe American Journal of Cardiology, Vol. 86, No. 4THE EFFECTS OF SYMPATHOMIMETICS ON THE CARDIOVASCULAR SYSTEM OF SHEEPClinical and Experimental Pharmacology and Physiology, Vol. 21, No. 10Effects of long-term xamoterol therapy on the left ventricular mechanical efficiency in patients with ischemic heart diseaseBasic Research in Cardiology, Vol. 84, No. 1The cardiac effects of adenosineProgress in Cardiovascular Diseases, Vol. 32, No. 1Effects of long-term xamoterol therapy on the left ventricular mechanical efficiency in patients with ischemic heart diseaseCan new inodilators displace digitalis in the therapy of congestive heart failure?Cardiovascular Drugs and Therapy, Vol. 2, No. 6Effects of adrenaline on the isolated heart of the trout (Salmo Gairdneri R.) before and after transfer from fresh water to sea waterComparative Biochemistry and Physiology Part C: Comparative Pharmacology, Vol. 87, No. 2Is inotropic therapy appropriate for patients with chronic congestive heart failure? Or is the digitalis leaf withering?Postgraduate Medical Journal, Vol. 62, No. 728Dopamine: Its potential for inducing ischemic left ventricular dysfunctionJournal of the American College of Cardiology, Vol. 6, No. 1Effects of Hypoxia and Acidosis on Fish Heart PerformanceEffects of a cardioselective beta1 partial agonist (corwin) on left ventricular function and myocardial metabolism in patients with previous myocardial infarctionThe American Journal of Cardiology, Vol. 51, No. 8The influence of inosine on the size of myocardial ischaemia and myocardial metabolism in the pigClinical Physiology, Vol. 2, No. 3Inotropic effects of adrenaline on the anoxic or hypercapnic myocardium of rainbow trout and eelJournal of Comparative Physiology ? B, Vol. 147, No. 1Protective effect of chronic versus acute cardiac denervation on contractile force during coronary occlusionAmerican Heart Journal, Vol. 102, No. 2Antiadrenergic Action sof Adenosine in the Heart: Possible Physiological SignificanceSites of Action and Production of Adenosine in the HeartEFFECTS OF ADRENALINE ON SOME ASPECTS OF ELECTRICAL AND MECHANICAL ACTIVITY IN THE FROG HEARTA DEVICE FOR RECORDING LEFT VENTRICULAR CONTRACTION AND ELECTROCARDIOGRAM IN NONWORKING ISOLATED PERFUSED RAT HEARTJapanese Journal of Pharmacology, Vol. 28, No. 2Myocardial IschemiaNew England Journal of Medicine, Vol. 296, No. 18The effect of hypoglycemia on myocardial ischemic injury during acute experimental coronary artery occlusion.Circulation, Vol. 51, No. 4 More from this issue > Volume 227Issue 2August 1974Pages 439-443 Copyright & PermissionsCopyright © 1974 by American Physiological Societyhttps://doi.org/10.1152/ajplegacy.1974.227.2.439PubMed4851758History Published online 1 August 1974 Published in print 1 August 1974 Metrics