Involvement of endogenous adenosine in ischaemic preconditioning in swine

Adenosine release and the subsequent activation of adenosine receptors are involved in ischaemic preconditioning in dogs and rabbits. In the present study, we investigated whether adenosine also mediates ischaemic preconditioning in swine. Swine were used since, due to the lack of an innate collateral circulation, infarct development in this species most closely resembles that observed in humans. In 36 enflurane-anaesthetized swine the impact of increased adenosine breakdown with exogenous porcine adenosine deaminase (5 IU/ml blood/min) on global and regional myocardial function (sonomicrometry), subendocardial blood flow (ENDO, microspheres) and infarct size (IS, triphenyl tetrazolium chloride staining following 90 min ischaemia and 120 min reperfusion) were analysed. Low-flow ischaemia for 90 min at an ENDO of 0.09±0.04 (mean±SD) ml/min/g caused an IS of 13.2±9.7% (n=8) of the area at risk. Ischaemic preconditioning by a cycle of 10 min low-flow ischaemia followed by 15 min reperfusion prior to the 90-min ischaemic period (ENDO=0.06±0.03 ml/min/g) reduced IS to 2.6±3.0% (n=11, P<0.05). The interstitial adenosine concentration (microdialysis) increased from 1.60±0.87 nmol/ml to above 10 M during ischaemia; with intracoronary adenosine deaminase, the interstitial adenosine concentration fell from 1.65±0.23 to 0.12±0.07 nmol/ml and did not increase during ischaemia. Adenosine deaminase per se did not alter IS after 90 min ischaemia (n=7, ENDO=0.08±0.04 ml/min/g, IS=12.1±6.9%) but abolished the beneficial effect of ischaemic preconditioning (n=10, ENDO=0.06±0.03 ml/min/g, IS=8.8±5.8%). For any given ENDO, IS was significantly reduced in the ischaemic preconditioned group compared with the other three groups. Global and regional myocardial function were comparable among all groups of swine. We conclude that endogenous adenosine mediates ischaemic preconditioning also in swine.