REPERFUSION-INDUCED ARRHYTHMIAS FOLLOWING ISCHEMIA IN INTACT RAT-HEART - ROLE OF INTRACELLULAR CALCIUM

Objective: The aim was to test the hypothesis that reperfusion induced arrhythmias are associated with major alterations in intracellular ca lcium ([Ca2+](i)) regulation. Methods: Intracellular calcium, epicardi al electrical potentials, and isovolumetric left ventricular pressure were simultaneously recorded in isolated perfused intact rat hearts du ring ischaemia (10 min) and reperfusion. [Ca2+](i) was measured using the bioluminescent calcium indicator aequorin. Results: Neither ventri cular tachycardia nor ventricular fibrillation occurred during ischaem ia. However, during the first minute of reperfusion ventricular tachyc ardia or fibrillation were frequently observed. Cellular calcium was a ltered by varying the perfusate calcium([Ca2+](o); 0.5, 1.0, and 3.0 m mol<bulletlitre(-1)). 0% (0/6), 50% (5/10), 91% (10/11), respectively, of hearts showed ventricular tachycardia, ventricular fibrillation, o r both upon reperfusion (P<0.001, 0.5 v 3.0 mmol . litre(-1)). At all [Ca2+](o) values examined, early ischaemia was associated with a rapid decrease in developed pressure and transient increase in the peak cal cium transient followed by a gradual decline and subsequent increase i n diastolic calcium during late ischaemia. The initiation of ventricul ar tachycardia/fibrillation upon reperfusion was immediately preceded by large increases in the amplitude of the calcium transient. These in creases in systolic calcium were not seen in hearts in which ventricul ar arrhythmias did not occur. Conclusions: The association between rep erfusion induced abrupt increases in peak calcium and the occurrence o f ventricular tachycardia or fibrillation suggests that intracellular calcium transients may have a significant role in initiating these ven tricular arrhythmias.