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Am J Physiol Heart Circ Physiol 279: H2166-H2175, 2000;
0363-6135/00 $5.00
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Vol. 279, Issue 5, H2166-H2175, November 2000

Intrinsic A1 adenosine receptor activation during ischemia or reperfusion improves recovery in mouse hearts

Jason Peart and John P. Headrick

Centre for Cardiovascular Research, Griffith University Gold Coast Campus, Southport QLD 4217, Australia

We assessed the role of A1 adenosine receptor (A1AR) activation by endogenous adenosine in the modulation of ischemic contracture and postischemic recovery in Langendorff-perfused mouse hearts subjected to 20 min of total ischemia and 30 min of reperfusion. In control hearts, the rate-pressure product (RPP) and first derivative of pressure development over time (+dP/dt) recovered to 57 ± 3 and 58 ± 3% of preischemia, respectively. Diastolic pressure remained elevated at 20 ± 2 mmHg (compared with 3 ± 1 mmHg preischemia). Interstitial adenosine, assessed by microdialysis, rose from ~0.3 to 1.9 µM during ischemia compared with ~15 µM in rat heart. Nonetheless, these levels will near maximally activate A1ARs on the basis of effects of exogenous adenosine and 2-chloroadenosine. Neither A1AR blockade with 200 nM 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) during the ischemic period alone nor A1AR activation with 50 nM N6-cyclopentyladenosine altered rapidity or extent of ischemic contracture. However, ischemic DPCPX treatment significantly depressed postischemic recovery of RPP and +dP/dt (44 ± 3 and 40 ± 4% of preischemia, respectively). DPCPX treatment during the reperfusion period alone also reduced recovery of RPP and +dP/dt (to 44 ± 2 and 47 ± 2% of preischemia, respectively). These data indicate that 1) interstitial adenosine is lower in mouse versus rat myocardium during ischemia, 2) A1AR activation by endogenous adenosine or exogenous agonists does not modify ischemic contracture in murine myocardium, 3) A1AR activation by endogenous adenosine during ischemia attenuates postischemic stunning, and 4) A1AR activation by endogenous adenosine during the reperfusion period also improves postischemic contractile recovery.

contracture; stunning


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