Adverse effects of chronic cardiac denervation in conscious dogs with myocardial ischemia.

Abstract

SUMMARY. The extent to which total chronic cardiac denervation protects the ischemic myocardium was investigated in conscious dogs. The major hemodynamic difference after coronary artery occlusion was that left ventricular end-diastolic pressure rose significantly more, P < 0.01, in the denervated group (12 ± 1.5 mm Hg) than in the normal group (4.4 ± 1.4 mm Hg). Blood flow (radioactive microspheres) in the ischemic endo-and epicardium fell to similar levels at 3-5 minutes after coronary occlusion, but was significantly less (P < 0.01) in denervated dogs at 3 hours after occlusion in the endo-(0.05 ± 0.01) and epicardium (0.30 ± 0.02 ml/min per g), than in the endo-(0.13 ± 0.03) and epicardium (0.42 ± 0.05 ml/min per g) in the normal group. A subgroup of normal dogs was also studied, with left ventricular end-diastolic pressure increased by volume loading to levels similar to those observed in the denervated group after coronary occlusion; in these dogs, blood flow was similar to that in the other two groups 3-5 minutes after coronary artery occlusion, but, at 3 hours, was significantly more depressed (P < 0.01) than that observed in normal dogs without volume loading in both endo-(0.03 ± 0.01) and epicardial (0.25 ± 0.03 ml/min per g) layers. Infarct size, as a fraction of the area at risk, was significantly greater (P < 0.05) in the denervated group (60 ± 4.3%) and in the subgroup of normal dogs with elevated left ventricular end-diastolic pressure (73 ± 5.8%), compared with the normal group without volume loading (37 ± 8.1%). Thus, in conscious dogs, total chronic cardiac denervation exerts an adverse effect on infarct size which may be related to the sustained elevation in left ventricular end-diastolic pressure and consequent impairment of collateral perfusion. (Circ Res 57: 383-392, 1985)

Cardiac Nerves Affect Myocardial Stunning Through Reactive Oxygen and Nitric Oxide Mechanisms

“…16 When a model of total cardiac denervation was used, the effects of total coronary occlusion were exacerbated. 24 The adverse effects observed in the latter model were likely due to the rise in LV end-diastolic pressure, which impeded collateral blood flow in dogs, effects that were not observed in pigs with regional myocardial denervation and partial coronary constriction. In the present model, LV end-diastolic pressure did not rise as much as in the prior canine study, 24 and importantly, collateral blood flow is not a feature of the porcine coronary circulation.…”

Ischemia-Induced Norepinephrine Release, but not Norepinephrine-Derived Free Radicals, Contributes to Myocardial Ischemia - Reperfusion Injury

“…Other studies, however, demonstrated that cardiac denervation had no protective effect 24 or rather had a detrimental influence. 25 These conflicting findings may come from differences in the experimental methods (ie, pharmacological or surgical denervation, whole body or local cardiac denervation, isolated or in situ hearts, anesthetized or conscious animals, and the animal species used in each experiment). Another important issue that could result in conflicting data might be differences in the duration of coronary artery occlusion.…”

Nicorandil Attenuates Ischemia-Reperfusion Injury Via Inhibition of Norepinephrine Release From Cardiac Sympathetic Nerve Terminals

“…Other studies, however, demonstrated that cardiac denervation had no protective effect on ischemic injury, 25) or rather had a detrimental influence. 26) These conflicting data may come from differences in the experimental methods used and in the duration of coronary artery occlusion. A prolonged duration of ischemia may mask a beneficial effect of cardiac denervation.…”