Using the isolated perfused rat heart with regional
ischemia and reperfusion, we have two antiarrhythmic interventions (the spin trap agent PBN [
N-tert-butyl-alpha-phenylnitrone] and perfusate
calcium reduction), administered just before reperfusion, to investigate mechanisms determining the vulnerability of the heart to reperfusion-induced
ventricular fibrillation. Hearts were subjected to regional
ischemia (5, 10, 20, 30 or 40 min) followed by reperfusion. Four groups were studied for each ischemic time: (i) control hearts with no antiarrhythmic intervention; (ii) hearts perfused with PBN (30 mumol/l) during the final 1 min of
ischemia and throughout reperfusion, (iii) hearts perfused with low-
calcium buffer (0.4 mmol/l) during the final 1 min of
ischemia and throughout reperfusion and (iv) hearts perfused with PBN (30 mumol/l) and low-
calcium (0.4 mmol/l) during the final 1 min of
ischemia and throughout reperfusion. In control hearts, a bell-shaped time-vulnerability curve was obtained with 0, 91, 67, 33 and 17% of the hearts exhibiting irreversible fibrillation during reperfusion after 5, 10, 20, 30 and 40 min of
ischemia, respectively. In the PBN group, the values were 8, 41 (P less than 0.05), 41, 33 and 8%, respectively. In the
calcium reduction group the values were 17, 50, 8 (P less than 0.05), 8 and 0, respectively. Thus, PBN caused a significant reduction in reperfusion-induced
ventricular fibrillation after 10 min of
ischemia but had no significant effect with reperfusion after 20 min of
ischemia. In contrast,
calcium reduction had no significant effect after 10 min of
ischemia but caused a significant reduction after 20 min of
ischemia. When PBN treatment with
calcium reduction were combined we obtained significant
anti-arrhythmic effects after both 10 min (P less than 0.05) and 20 min (P less than 0.05) of
ischemia. The additive effects of these two interventions, and the different ischemic-times after which they are most effective, has led us to propose that multiple triggers, each with different underlying mechanisms may be capable of initiating events which lead to
ventricular fibrillation.