A1 adenosine receptor overexpression decreases stunning from anoxia-reoxygenation:: role of the mitochondrial KATP channel

Myocardial A, adenosine receptor (AIAR) overexpression protects hearts from ischemia-reperfusion injury; however, the effects during anoxia are unknown. We evaluated responses to anoxia-reoxygenation in wild-type (WT) and transgenic (Trans) hearts with similar to200-fold overexpression of A(1)ARs. Langendorff perfused hearts underwent 20 min anoxia followed by 30 min reoxygenation. In WT hearts peak diastolic contracture during anoxia was 45 +/- 3 mmHg, diastolic pressure remained elevated at 18 +/- 3 mmHg after reoxygenation, and developed pressure recovered to 52 +/- 4% of pre-anoxia. A(1)AR overexpression reduced hypoxic contracture to 29 +/- 4 mmHg, and improved recovery of diastolic pressure to 8 1 mmHg and developed pressure to 76 +/- 3 % of pre-anoxia. Mitochondrial K-ATP blockade with 100 muM 5-hydroxydecanoate (5-HD) increased hypoxic contracture to 73 +/- 6 mmHg in WT hearts, reduced post-hypoxic recoveries of both diastolic (40 +/- 5 mmHg) and developed pressures (33 +/- 3 %). In contrast, 5-HD had no effect on hypoxic contracture (24 8 mmHg), or post-hypoxic diastolic (10 +/- 2 mmHg) and developed pressures (74 3 %) in Trans hearts. In summary, (i) A(1)AR overexpression improves myocardial tolerance to anoxia-reoxygenation, (ii) intrinsic mitochondrial K-ATP channel activation decreases hypoxic contracture and improves functional recovery in wild-type hearts, and (iii) mitochondrial K-ATP channels do not appear to play a major role in the functional protection from anoxia afforded by A(1)AR overexpression.