Abstract 1568: Loss of Ischemic Postconditioning in the Mouse Hearts Lacking Adenosine A1 or Bradykinin B2 Receptors
Background: Ischemic postconditioning (PostC) is a recently described cardioprotective modality against reperfusion injury, through a series of brief episodes of reperfusion/ischemia at the very onset of reperfusion. It has been well recognized that PostC can activate cellular signaling cascade, in which the role of G protein-coupled membrane receptors serving as upstream triggers of PostC remains to be established. Hence the goal of this study was to determine a definitive role of adenosine A1 receptors (A1) and bradykinin B1 or B2 receptors (B1 or B2) in PostC, using gene knockout (KO) mice.
Methods & Results: The hearts isolated from adult male C57BL/6J wild-type mice (C57-WT) or A1, B1, or B2 KO mice (n=7–9 per group) were subjected to 20 min of zero-flow global ischemia and 30 min of reperfusion with or without PostC in a Langendorff isolated, buffer-perfused heart model. PostC, consisted of 6 cycles of 10 sec of reperfusion and 10 sec of ischemia, significantly reduced myocardial infarct size (22.8±3.1%, Mean±SEM) as compared with C57-WT controls (35.1±2.8%, P<0.05). As shown in Figure⇓ below, the infarct-limiting protection of PostC was absent in A1-KO (34.9±2.7%) or B2-KO (33.3±1.7%) and was partially attenuated in B1-KO (25.6±2.9%) mice, as compared with the corresponding non-PostC controls under same genetic background (P>0.05). However, cardiac contractile function and coronary flow at the end of reperfusion were not significantly altered by PostC.
Conclusion: PostC-induced infarct size reduction in globally ischemic mouse hearts is triggered by activation of multiple G protein-coupled membrane receptors, which include A1, B2, and, to a lesser extent, B1 receptors.