Effects of ganglionic blockade on noradrenaline release and cell injury in the acutely ischemic rat myocardium.
We investigated the mechanisms responsible for ischemia-induced myocardial noradrenaline release in pentobarbitone-anaesthetized rats with left coronary artery occlusion. By means of tissue analysis of catecholamines and the Hillarp-Falck fluorescence histochemical technique for visualizing catecholamines in tissues, we studied the effect of a ganglionic blocker (chlorisondamine 0.1 mg/kg i.v.) on the ischemia-induced changes of the myocardial adrenergic nerve endings. In addition, the myocardial creatine kinase activity and potassium content were determined to estimate the extent of ischemic cell injury. In rats treated with either saline or chlorisondamine, the tissue noradrenaline content of the ischemic left ventricle was markedly reduced after 2.5 h of coronary ligation. In saline-treated rats 0.5 h of ischemia caused a slight decrease in left ventricular noradrenaline content, and this tended to be even less marked in chlorisondamine-treated animals. The changes in catecholamine fluorescence of the acutely ischemic myocardium seen after ganglionic blockade were essentially the same in both groups, but the size of the regions with reduced catecholamine fluorescence was more variable in the chlorisondamine-treated rats. Chlorisondamine caused a reduction in arterial blood pressure and heart rate and tended to reduce the degree of ischemic cell damage. We conclude that in our model the decrease in myocardial noradrenaline content after 2.5 h of ischemia is largely due to a local, nerve impulse--independent release of noradrenaline caused by ischemic changes in the tissue. The acute release of noradrenaline seen during 0.5 h of ischemia may be the combined result of local, ischemia-induced release of noradrenaline and an increased sympathetic nerve activation of the heart.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002714:Chlorisondamine / Q000494:pharmacology; D003327:Coronary Disease / Q000378:metabolism*; D003331:Coronary Vessels / Q000502:physiology; D003402:Creatine Kinase / Q000378:metabolism; D004837:Epinephrine / Q000378:metabolism; D005730:Ganglionic Blockers / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D005730:Ganglionic Blockers; D003402:Creatine Kinase; D002714:Chlorisondamine; D011188:Potassium; D009638:Norepinephrine; D004837:Epinephrine