“Preconditioning” the heart with brief periods of ischemia protects it from sustained ischemia such as can occur during surgical correction of congenital heart disease. One possible mechanism of this protection involves the activation of A1 adenosine receptors. To investigate the role of A1 adenosine receptors in ischemic preconditioning, wild-type and transgenic mouse hearts with increased A1 receptors were studied. The effect of preconditioning on recovery from sustained ischemia was examined in isolated Langendorff hearts in each group. Myocardial injury was assessed by postischemic functional recovery (% of baseline developed tension,% DT) and quantitation of enzyme markers of cell death in coronary effluent (creatine kinase, CK and lactate dehydrogenase, LDH; u/L/gm for both). Transgenic overexpression of A1 receptors resulted in greater recovery of developed tension (45% vs 26% p<0.05, ANOVA) and nearly undetectable levels of CK and LDH compared to wild-type (table). Preconditioning wild-type hearts improved recovery of developed tension similar to A1 receptor overexpression (38% vs 45%, n.s.) and also resulted in very low levels of CK and LDH. Interestingly, preconditioning in transgenic hearts caused no further improvement of function (39% vs 45%, n.s.). In summary, both preconditioning and transgenic overexpression of A1 adenosine receptors result in similar improvement of functional recovery and decreased cell death following ischemia. The inability of preconditioning to further enhance the functional recovery in transgenic mice suggests that hearts with A1 adenosine receptor overexpression may already be preconditioned.

Table 1 No caption available.
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