Cardioprotective effect of diadenosine tetraphosphate (AP4A) preservation in hypothermic storage and its relation with mitochondrial ATP-sensitive potassium channels

Background, The Preconditioning effect of diadenosine tetraphosphate (AP4A) was reported in ischemia/reperfused hearts, but its effect in heart preservation was unknown. According to the possible role of mitochondrial ATP-sensitive potassium channel (mK(ATP) channel) in the effect of ischemic preconditioning, the contribution of mK(ATP), channel to the effect of AP4A was tested; Methods. Isolated rat hearts were arrested and preserved by Eurocollin's (EC) solution at 4 degrees C for 8 hr, AP4A (80 mu M) or AP4A with the 5-hydroxydecanoic acid (100 mu M), a selective inhibitor of the mK(ATP), channel, was added into the EC solution. The preischemic and postischemic cardiac functions were evaluated on a buffer-perfused Langendorff apparatus before storage and after 20 min of reperfusion. Results. AP4A administration improved the recovery of poststorage cardiac functions (tho rate-pressure production, left ventricular systolic pressure, heart rate, coronary flow rate, and derivative of left ventricular systolic pressure; P<0.05) and reduced the Leakage of lactate dehydrate and creatine kinase during reperfusion, compared with EC alone. Those effects of AP4A were completely reversed by 5-hydroxydecanoie acid administration in combination subjects. Conclusion. AP4A administration protects the heart through opening of the mK(ATP) channel during hypothermic preservation. Thus, addition of AP4A into cardioplegia may be a novel method of ischemic preconditioning in the transplantation context.