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Sex differences in myocardial infarct size are abolished by sarcolemmal K_ATP channel blockade in rat

Department of Integrative Physiology, University of Colorado at Boulder, Boulder, Colorado

Submitted 8 December 2005 ; accepted in final form 24 January 2006

This study was conducted to examine the relationship between myocardial ATP-sensitive potassium (K_ATP) channels and sex differences in myocardial infarct size after in vitro ischemia-reperfusion (I/R). Hearts from adult male and female Sprague-Dawley rats were excised and exposed to an I/R protocol (1 h of ischemia, followed by 2 h of reperfusion) on a modified Langendorff apparatus. Hearts from female rats showed significantly smaller infarct sizes than hearts from males (23 ± 4 vs. 40 ± 5% of the zone at risk, respectively; P < 0.05). Administration of HMR-1098, a sarcolemmal K_ATP channel blocker, abolished the sex difference in infarct size (42 ± 4 vs. 45 ± 5% of the zone at risk in hearts from female and male rats, respectively; P = not significant). Further experiments showed that blocking the K_ATP channels in ischemia, and not reperfusion, was sufficient to increase infarct size in female rats. These data demonstrate that sarcolemmal K_ATP channels are centrally involved in mechanisms that underlie sex differences in the susceptibility of the intact heart to I/R injury.

heart; ischemia; reperfusion

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