adrenergic system in the ischemic heart: evidence for a protective role induced by cardiac gene modulation

ABSTRACT

Twenty-one rabbits' isolated perfused hearts were used in this study. Animals were divided into three groups. Group 1 [control, non preconditioned group] received no treatment and subjected to ischemia reperfusion protocol designed for all groups. Group 2 [PE group] was preconditioned by alpha-1 adrenoceptor agonist [50 mug/kg phenylephrine [PE]] pretreatment 24 hours before induction of ischemia. Group 3 [PE and Pr group] received alpha-1 adrenergic blocker prazosin [Pr] in a dose of 50 mug/kg 15 minutes prior to administration of PE. 24 hours later, hearts were isolated and perfused in Langendorff mode. All hearts were subjected to 30 minutes of no flow ischemia, followed by 120 minutes reperfusion. The following parameters were measured at base line, during and at the end of 120 minutes reperfusion period Left ventricular developed pressure [LVDP], heart rate [HR], rate pressure product [RPP], peak rate of maximum left ventricular pressure rise [dP/dTmax] and peak rate of pressure fall [dP/dTmin]. ECG changes were recorded. Expression of iNOS was also detected in left ventricular tissue of all studied groups at the end of reperfusion by reverse transcriptase polymerase chain reaction. Isolated hearts after phenylephrine pretreatment significantly improved post ischemic cardiac performance as indicated by higher LVDP, HR, RPP, dP/dTmax and dP/dTmin and lower St segment elevation as compared to control group. Increased expression of iNOS mRNA was also demonstrated. Prazocin administration completely abrogated the improved functional recovery observed with PE alone. The phenylephrine induced expression of iNOS mRNA was attenuated when hearts received prazocin