Role of adenosine in the cardioprotective effect of ischemic preconditioning in the isolated rabbit hearts

Kim, Dae Joong; Hahn, Jang Hee; Kim, Hyun; Kim, Ho Dirk

Abstract

This study was designed to provide a evidence that adenosine-mediated activation of protein kinase C and K(ATP) channel was a important step on the cardioprotection mechanism of ischemic preconditioning (IP). Isolated Langendorff-perfused New Zealand White rabbit hearts were subjected to 45 min of global ischemia (I) and 120 min reperfusion (R) with or without IP. IP was induced by a single dose of 5 min I and 10 min R. Part of the IP hearts was treated with non-specific adenosine receptor blocker 8-sulfophenyltheophylline (SPT; 100 micromol) and K(ATP) channel blocker glibenclamide (10 micromol) 5min before IP, respectively. To determine the effect of IP, we measured the left ventricular function, infarct size, adenosine concentration in the coronary flow and total protein kinase C activity. PKC activity was determined by (32)P-gamma-ATP incorporation into PKC specific peptide. IP enhanced improvement of functional recovery and caused a decrease in the infarct size from 19.9+/-0.05% in the ischemic-control group to 5.5+/-1.39% in the IP group (p<0.05). In the SPT- and glibenclamid-treated hearts, however, these anti-ischemic effect was disappeared. Adenosine release from the cardiac tissue was abruptly increased to 10~20 folds baseline just after IP. Cytosolic PKC activity decreased significantly in the IP hearts, while in the membrane fraction, activity was increased (45 min I, p<0.05; 120 min R, p<0.01). In the SPT-treated hearts, IP did not make those activity changes of PKC. These data suggest that adenosine induced the anti-ischemic effect via PKC activation. And it also show that K(ATP) channel may work on the protection as a final effector.