Objective: 

This study was performed to assess the relative effect of sarcolemmal and mitochondrial ATP-dependent K⁺ channel (KATP) modulation on ischemia reperfusion (I/R)-induced arrhythmias in different gender of rats. We compared the effect of a selective sarcolemmal KATP blocker, HMR 1098; a selective mitochondrial KATP opener, diazoxide; a nonselective KATP opener, pinacidil and the combination of pinacidil with HMR 1098 on the incidence and duration of ventricular arrhythmias in 2 groups: anesthetized males (n = 31) and females (n = 31).

Methods: 

Ischemia and reperfusion was produced by occluding the left main coronary artery of anesthetized Sprague-Dawley rats for 6 minutes followed by re-opening of the artery for 6 minutes.

Results: 

The arrhythmia score and the duration of arrhythmias were significantly reduced by HMR 1098, diazoxide, and pinacidil in male rats. The combination of pinacidil with HMR 1098 did not change the antiarrhythmic effect of pinacidil (Arrhythmia scores: HMR 1098, 1.5±0.2; diazoxide, 1.6±0.4; pinacidil, 1.1±0.3; and pinacidil+HMR 1098, 1.5±0.2 vs control, 3.1±0.6; P<0.05). The duration of arrhythmas was shorter in females. Drug treatments were not effective in decreasing arrhythmias in female groups to the same extent as in the male group.

Conclusions: 

Results of the current study indicate that both mitochondrial KATP activation and sarcolemmal KATP inhibition exert antiarrhythmic action in male rats. The antiarrhythmic effect of pinacidil does not depend on the sarcolemmal KATP opening. These results also indicate that KATP modulators show no discernable effect in female rats due to the already low incidence of arrhythmias in females.