| Budget Amount *help |
¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1994: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1993: ¥700,000 (Direct Cost: ¥700,000)
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| Research Abstract |
ADENOSINE MEDIATES ANTIARRHYTHMIC EFFECT OF ISCHEMIC PRECONDITIONING IN ISOLATED RAT HEARTS
Adenosine appears to mediate the preconditioning-induced reduction in infar ct size in rabbits and dogs, however, little is known about the role of adenosine in preconditioning-induced protection against ischemia-induced arrhythmias. We compared the protective effects of preconditioning induced by 2 cycles of 5-minute global ischemia and 2 cycles of 5-minute perfusion with adenosine (100 muM) or the A1 receptor agonist 2-chloro-N6-cyclopentyladenosine (CCPA,100nM) for protection against ischemia-induced arrhythmias in Langendorff perfused rat hearts. Preconditioning reduced the incidence of VT from 100 to 58% and the incidence of sustained VT or VF from 92 to 33%. Perfusion with adenosine reduced the incidence of VT from 100 to 55%, the incidence of VF from 67 to 9% and the incidence of sustained VT or VF from 92 to 9%. CCPA reduced the incidence of sustained VT or VF from 92 to 25%. These inter
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ventions provided true reduction in the severity of arrhythmias rather than the delay of the onset of arrhythmias. Our results suggest that, adenosine and the A1 receptor mediate ischemic preconditioning-induced protection against ischemiainduced arrhythmias in rats.
REDUCTION OF REPERFUSION-INDUCED ARRHYTHMIAS BY ATP-DEPENDENT POTASSIUM CHANNEL OPENER
ATP-dependent potassium (KATP) channel opener has been shown to be protective in ischemic-reperfused myocardium. To test anti-arrhythmic potentials of this agent, we examined the effect of Y-26763, KATP channel opener, on reper fusion-induced arrhythmias. Isolated perfused rat hearts were subjected to 10-min regional ischemia and 5 min of reperfusion, and all heats were paced at 350 beats/min. Y-26763 (0.3,1.0 mumol/l) was infused for 5 min just prior to regional ischemia. Perfusion with 1 mumole Y-26763 significantly reduced the incidence of VPC,VT,and VF to 42%. This compound also significantly reduced the mean duration of reperfusion-induced arrhythmias. Duration of VT was decreased from 6.5 to 1.8 seconds and that of VF from 120 seconds to 20 seconds. These results suggest that this agent possesses antiarrhythmic effects on reperfusion-induced arrhythmias. Less
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