The platelet activating factor triggers preconditioning-like cardioprotective effect via mitochondrial K-ATP channels and redox-sensible signaling.

Endogenous platelet activating factor (PAF) is involved in heart ischemic preconditioning. PAF can also afford pharmacological preconditioning. We studied whether mitochondrial-ATP-sensitive K(+) (mK(ATP)) channels and reactive oxygen species (ROS) are involved in PAF-induced cardioprotection. In Group 1 control hearts, Langendorff-perfused rat hearts underwent 30 min ischemia and 2 hours of reperfusion. Group 2 hearts, before ischemia, were perfused for 19 min with PAF (2x10(-11) M); Groups 3 and 4 hearts were co-infused with PAF and N-acetyl-L-cysteine or 5-hydroxydecanoate to scavenge ROS or to block mK(ATP) channels, respectively. Left ventricular pressure and infarct size were determined. PAF-pretreatment reduced infarct size (33 +/- 4% vs 64 +/- 4.6 % of the area at risk of control hearts) and improved pressure recovery. Infarct-sparing effect of PAF was abolished by N-acetyl-L-cysteine and 5-hydroxydecanoate. Thus, the cardioprotective effect exerted by PAF-pretreatment involves activation of mK(ATP) channels and redox signaling in pre-ischemic phase.