PRE-CLAMP CARDIOPROTECTION BY PROTEIN-KINASE-C (PKC) INHIBITOR IMPROVES LEFT-VENTRICULAR FUNCTION FOLLOWING CANINE NORMOTHERMIC ARREST

Since protein kinase C (PKC) has been proven to be a mediator of neutr ophil activation and of intracellular calcium homeostasis, its inhibit ion could protect the myocardium from the deleterious effects of ische mic/reperfusion inury (IRI). The principal objective of this study was to evaluate the efficacy of the PKC inhibitor SPC-100270 (2S,3S)-2-am ino, 3-octadecanediol in a canine model of IRI. A double-blind study w as conducted in which 19 coonhound dogs received either SPC-100270 or a vehicle before going on cardiopulmonary bypass (CPB). After 60 minut es of global normothermic (37 degrees C) cardiac arrest (cross-clamp t ime 65-81 minutes for SPC-100270 and 65-72 minutes for control) and di scontinuation of CBP, an epicardial short axis view echocardiogram was performed and reviewed by a double-blinded observer to determine the ejection fraction CEF). EF value exceeded 20% in 5 out of 9 SPC-100270 animals (27%-44%) and in 0 of 10 controls (0%-16%). These data show t hat SPC-100270 significantly (p=0.01 by Fisher's Exact Test) increased the probability that the animals would exhibit an EF greater than 20% .