Reperfusion induced arrhythmias following ischaemia 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 calcium ([Ca2+]i) regulation.


METHODS
Intracellular calcium, epicardial electrical potentials, and isovolumetric left ventricular pressure were simultaneously recorded in isolated perfused intact rat hearts during ischaemia (10 min) and reperfusion. [Ca2+]i was measured using the bioluminescent calcium indicator aequorin.


RESULTS
Neither ventricular tachycardia nor ventricular fibrillation occurred during ischaemia. However, during the first minute of reperfusion ventricular tachycardia or fibrillation were frequently observed. Cellular calcium was altered by varying the perfusate calcium ([Ca2+]o; 0.5, 1.0, and 3.0 mmol.litre-1). 0% (0/6), 50% (5/10), 91% (10/11), respectively, of hearts showed ventricular tachycardia, ventricular fibrillation, or 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 calcium transient followed by a gradual decline and subsequent increase in diastolic calcium during late ischaemia. The initiation of ventricular tachycardia/fibrillation upon reperfusion was immediately preceded by large increases in the amplitude of the calcium transient. These increases in systolic calcium were not seen in hearts in which ventricular arrhythmias did not occur.


CONCLUSIONS
The association between reperfusion induced abrupt increases in peak calcium and the occurrence of ventricular tachycardia or fibrillation suggests that intracellular calcium transients may have a significant role in initiating these ventricular arrhythmias.
Brooks
W W
WW
Veterans Affairs Medical Center, MA, USA.
Conrad
C H
CH
Morgan
J P
JP
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D004594:Electrophysiology; D066298:In Vitro Techniques; D007424:Intracellular Fluid / Q000378:metabolism*; D008297:Male; D017202:Myocardial Ischemia / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D010477:Perfusion; D051381:Rats; D011921:Rats, Inbred WKY; D017725:Ventricular Pressure / Q000187:drug effects
D002118:Calcium