PGI2 Prevents Ischemia-Induced Alterations in Cardiac Catecholamines Without Influencing Nerve-Stimulation-Induced Catecholamine Release in Nonischemic Conditions

Abstract

Summary Acute myocardial ischemia was produced in rabbit Langendorff hearts by ligation of the left anterior descending coronary artery for 2 h. This was accompanied by a significant increase in creatine kinase-specific activity of the ischemic myocardium as compared to sham-operated nonischemic controls (p ± 0.05) and a significant decrease (p ± 0.01) in ATP levels from 2.25–0.29 mol/g wet wt. in the nonischemic area to 0.95 ± 0.21 mol/g wet wt in the ischemic area, indicating a considerable degree of tissue damage. There was a decrease in the norepinephrine ratio between infarcted and noninfarcted myocardium from 1.08 ± 0.08 in sham-operated controls to 0.66 ± 0.06 in ischemic hearts (p ± 0.01). Histochemistry revealed a nearly complete loss of fluorescence in perivascular adrenergic nerves in the ischemic area. Infusion of prostacyclin (PGI₂) (1.1 nmol min), starting 10 min prior to ischemia, abolished the increase in creatine kinase activity (p ± 0.05) and the decrease in ATP levels of the ischemic myocardium (p ± 0.05). Furthermore, PGI₂ prevented the ischemia-induced alterations in catecholamine content and the decrease in adrenergic fiber fluorescence. PGI₂ did not significantly influence myocardial dynamics and oxygen consumption. To determine the effect of PGI₂ on nerve stimulation-induced catecholamine release, a separate group of Langendorff rabbit hearts with intact right sympathetic nerves were stimulated twice for 1 min at 0 and 13 min. PCI₂ at 30 nM 3μM had no significant effect on catecholamine overflow when compared to control hearts. It is concluded that PGI₂ exerts a stabilizing effect on cell membranes that prevents ischemia-induced destruction of adrenergic nerve endings, This cytoprotective effect is restricted to the ischemic area and does not interfere with the physiological nerve-stimulation-induced norepinephrine release.