Effect of substrate on release of myocardial norepinephrine and ventricular arrhythmias following reperfusion of the ischemic isolated working rat heart.

Isolated rat hearts were prelabeled with 3H-norepinephrine (NE), submitted to coronary artery ligation, and perfused through the left atrium with a modified Krebs-Henseleit solution containing 3 mM potassium and four different substrates: 5.5 mM glucose, 5.5 mM glucose plus 0.15 or 0.5 mM palmitate bound to albumin in a molar ratio of 6:1, and 11 mM glucose. The coronary artery ligature was removed after 30 min of perfusion of the ischemic working heart. With all substrates the release of radioactivity in the coronary effluent remained relatively constant during the ischemic period. Reperfusion was associated with a sudden release of radioactivity and of 3H-NE, but the intensity of the efflux was influenced by the nature of the perfusion substrate. The highest release was observed with 5.5 mM glucose and the lowest release in the presence of 0.15 mM palmitate. Intermediate and similar releases were seen with the two other substrates. On reperfusion of the ischemic heart, ventricular arrhythmias (tachycardia and fibrillation) were very marked with 5.5 mM glucose and in the presence of 0.5 mM palmitate. They were significantly delayed in the presence of 0.15 mM palmitate and almost absent with 11 mM glucose. These results do not show a relationship between the amount of NE liberated during the post-ischemic period and the extent of ventricular reperfusion arrhythmias. We conclude that either myocardial NE is not implicated in the genesis of reperfusion arrhythmias or that cardiac vulnerability to the arrhythmogenic effect of NE is influenced by the metabolic state of the myocardium, which is dependent on the nature of the perfusion substrate.