Ischaemic preconditioning enhanced recovery of postischaemic contractile function (42.3% vs 19.7%; p<0.02), an effect not mediated by adenosine in the isolated rat heart.
Does adenosine mediate the cardioprotective effects of ischaemic preconditioning in the isolated rat heart?
The cardioprotective effects of ischaemic preconditioning are not mediated by adenosine in the isolated rat heart, and transient A1 adenosine receptor agonist treatment can exacerbate postischaemic contractile dysfunction.
Absolute Event Rate: 42.3% vs 19.7%
p-value: p=<0.02
OBJECTIVE: The aim was to test the hypothesis that adenosine mediates the cardioprotective effects of ischaemic preconditioning in the isolated rat heart. METHODS: Transient exposure of the hearts to adenosine and the A1 selective agonist, PIA, were tested for the ability to mimic the cardioprotective effects of ischaemic preconditioning in hearts that underwent 40 min normothermic ischaemic followed by 30 min reperfusion. Treated hearts were perfused with 10 or 50 microM adenosine or 10(-7) M R-phenylisopropyladenosine (PIA) for 5 min followed by a 5 min washout period. Preconditioned hearts underwent 5 min of ischaemia and 5 min of reflow prior to the 40 min ischaemic period. The ability of the adenosine receptor antagonist, BW A1433U, to inhibit the cardioprotective effects of ischaemic preconditioning was also tested. The effects of these treatments on metabolite levels and postischaemic haemodynamic function were assessed. RESULTS: Adenosine (50 microM), but not PIA, resulted in enhanced accumulation of lactate after 40 min ischaemia: 122(SEM 8) v 96(5) nmol.mg-1 protein in control hearts (p < 0.002). Adenosine and PIA treatments did not significantly affect myocardial acidosis during ischaemia. Postischaemic contractile function (as assessed by percent recovery of the heart rate x developed pressure) was lower in 50 microM, but not 10 microM, adenosine treated hearts 8.8(2.2) and PIA treated hearts 11.9(2.5) than in control hearts 20.4(3.6) (p < 0.01). Ischaemic preconditioning (1) lowered glycogen levels prior to the 40 min ischaemic period 57(6) v 110(18) nmol glucosyl units.mg-1 protein; p < 0.01; (2) lowered lactate levels at the end of the 40 min ischaemic period 61(4) v 104(5) nmol.mg-1 protein; (3) preserved myocardial pH during ischaemia 6.69(0.07) v 6.40(0.07); p < 0.01; and (4) enhanced recovery of postischaemic contractile function 42.3(4.4)% v 19.7(6.0)%; p < 0.02. BW A1433U did not prevent these effects of ischaemic preconditioning. CONCLUSIONS: The cardioprotective effects of ischaemic preconditioning are not mediated by adenosine released during the preconditioning period in the isolated rat heart. Also, transient treatment of the heart with A1 adenosine receptor agonists can exacerbate postischaemic contractile dysfunction.
Asimakis et al. (1993) studied Myocardial ischaemia. Adenosine and ischaemic preconditioning vs. Control hearts was evaluated on Postischaemic contractile function (percent recovery of heart rate x developed pressure) (p=<0.02). Ischaemic preconditioning enhanced recovery of postischaemic contractile function (42.3% vs 19.7%; p<0.02), an effect not mediated by adenosine in the isolated rat heart.