The role of adenosine in ischemic preconditioning in swine.

Abstract

Previous studies suggest that increases in adenosine (ADO) may mediate the protective effects ischemic preconditioning (PC). We tested this hypothesis using an open-chest, isoflurane anesthetized micropig model and six experimental groups: (1) control underwent 60 minutes of coronary artery occlusion (CAO) and 3 hours of reperfusion (REP), (2) preconditioned (PC) with 10 minutes of CAO and REP prior to sustained CAO, (3) pentostatin (PS, 2-deoxycoformycin, 0.2 mg/Kg IV 30$\sp\prime$ prior to CAO), an inhibitor of adenosine deaminase (ADA), (4) PS treatment with pacing of heart rates, (5) PD 126,280 (5.0 $\mu$g/kg IV 20$\sp\prime$ prior to CAO), an A1 selective adenosine receptor agonist, and (6) 8-sulfophenyl theophilline (SPT, 5.0 $\mu$g/kg IV 10$\sp\prime$ prePC), a non-specific adenosine receptor antagonist. Infarct size was determined with negative tetrazolium salt staining, and expressed as a percentage of the region at risk (RAR).(DIAGRAM, TABLE OR GRAPHIC OMITTED...PLEASE SEE DAI)These results indicate that PC, ADA inhibition, and A1 receptor activation attenuate myocardial ischemic injury. To determine if the cardioprotective effects of ADA inhibition or PC could be attributed to augmentation of regional adenosine (ADO), direct measurement of interstitial fluid (ISF) ADO was made using microdialysis probes in a separate group of animals. ADO concentrations ($\mu$M) in control (n = 6), pentostatin treated (n = 6), and PC animals (n = 6) were measured.(DIAGRAM, TABLE OR GRAPHIC OMITTED...PLEASE SEE DAI)The data suggest that preischemic stimulation of ADO receptors is as effective as elevations in ISF ADO during prolonged ischemia in limiting the development of irreversible myocardial injury. These results indicate that preischemic increases in ISF ADO, and subsequent A1 stimulation, mediates PC.