ROLE OF ADENOSINE IN ISOFLURANE-INDUCED CARDIOPROTECTION

Background: This investigation tested the hypothesis that adenosine (A (1)) receptor blockade modulates the cardioprotective effects of isofl urane. Methods: Hemodynamics and percentage segment shortening (%SS) i n the left anterior descending coronary artery (LAD) perfusion territo ry were evaluated in barbiturate-anesthetized dogs (n = 31) at selecte d intervals after pretreatment with the selective A(1) receptor antago nist (8-cyclopentyl-1,3,dipropylxanthine; DPCPX 0.8 mg/kg, intravenous ly) or drug vehicle in the presence or absence of 1 minimum alveolar c oncentration (;MAC) isoflurane. Dogs were subjected to five 5-min occl usions and reperfusions of the LAD, followed by 180 min of final reper fusion. Isoflurane was administered for 30 min before and during LAD o cclusions and reperfusions and was discontinued at the onset of final reperfusion. Two other groups of dogs (n = 17) were used to measure in terstitial concentrations of purines in the LAD region using a microdi alysis technique in the presence and absence of isoflurane. Results: D ogs receiving drug vehicle or DPCPX exhibited no recovery of %SS after 180 min of reperfusion (-5 +/- 7 and 5 +/- 11% of baseline, respectiv ely, +/-SEM). In contrast, dogs receiving isoflurane alone demonstrate d complete recovery of %SS at 60 min after reperfusion, DPCPX pretreat ment partially attenuated isoflurane-induced enhancement of recovery o f %SS (34 +/- 11% of baseline 180 min after reperfusion; P < 0.05). In terstitial purine concentrations were increased during multiple occlus ions and reperfusions of the LAD in dogs not receiving isoflurane, but they were unchanged by coronary artery occlusion and reperfusion in d ogs receiving isoflurane. Conclusions: The results indicate that isofl urane-induced cardioprotection in stunned myocardium is partially medi ated by adenosine type 1 receptor activation and is accompanied by dec reases in endogenous adenosine release.