Mitochondrial ATP-sensitive potassium channels play a role in reducing both myocardial infarction and reperfusion arrhythmia in romote ischemic preconditioned hearts

Abstract

Background :

Mitochondrial ATP-sensitive potassium (mKATP) channels play a role in reperfusion arrhythmias (RAs) in ischemia-reperfusion (I/R) injury. Evidence suggests that remote ischemic preconditioning (RIPC) reduces RAs, however not much is known on the mechanistic role of mKATP in RIPC. We evaluated whether mKATP channels are associated with reducing arrhythmia and infarct size in RIPC.

Methods : Isolated rat hearts received 30 minutes of regional ischemia followed by 2 hours of reperfusion through the Langendorff perfusion system. RIPC was induced by 3 cycles of 5 minutes occlusion and 5 minutes release of the bilateral femoral artery. The animals were randomly divided into 4 groups as follows: 1) CON, I/R injury but not RIPC, 2) RIPC, 3) HD+RIPC, pretreatment of the selective mKATP channel blocker, 5-hydroxydecanoate (5-HD), in RIPC, and 4) HD, pretreatment of 5-HD in CON. Cardiodynamics and infarct size were determined. The severity of arrhythmia was quantitated via the Curtis and Walker scoring system as well as the Lepran scoring system.

Results : RIPC significantly reduced the infarct size over AR (25.7 ± 2.6%) compared to CON (37.0 ± 2.6%, P < 0.05). The selective mKATP channel blocker 5-HD significantly inhibited the infarct-reducing effect of RIPC (39.3 ± 3.0%, P < 0.05 vs. RIPC). Additionally, RIPC significantly reduced the arrhythmia score compared to CON (14.6 ± 1.9 to 8.7 ± 0.4, P = 0.023, by Curtis and Walker’s system, 16.1 ± 2.1 to 9.1 ± 0.5, P = 0.006, by Lepran’s system). The anti-arrhythmic effect of RIPC was blocked by 5-HD (15.5 ± 1.6 and 16.0 ± 1.2, by Curtis and Walker’s and Lepran’s system, respectively).

Conclusions : The selective mKATP channel blocker, 5-HD, inhibited the infarct-limitation and anti-arrhythmic effect of RIPC. The mKATP channels play a role in the reduction of both infarct size and RAs in RIPC.