Pre-clamp cardioprotection by protein kinase C (PKC) inhibitor improves left ventricular function following canine normothermic arrest

J Cardiovasc Surg (Torino). 1996 Apr;37(2):141-3.

Abstract

Since protein kinase C (PKC) has been proven to be a mediator of neutrophil activation and of intracellular calcium homeostasis, its inhibition could protect the myocardium from the deleterious effects of ischemic/reperfusion inury (IRI). The principal objective of this study was to evaluate the efficacy of the PK inhibitor SPC-100270 (2S,3S)-2-amino, 3-octadecanediol in a canine model of IRI. A double-blind study was conducted in which 19 coonhound dogs received either SPC-100270 or a vehicle before going on cardiopulmonary bypass (CPB). After 60 minutes of global normothermic (37 degree C) cardiac arrest (cross-clamp time 65-81 minutes for SPC-100270 and 65-72 minutes for control) and discontinuation of CBP, an epicardial short axis view echocardiogram was performed and reviewed by a double-blinded observer to determine the ejection fraction (EF). 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 that SPC-10027 significantly (p=0.01 by Fisher's Exact Test) increased the probability that the animals would exhibit an EF greater than 20%.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Cardiopulmonary Bypass
  • Dogs
  • Double-Blind Method
  • Echocardiography
  • Electrocardiography
  • Enzyme Inhibitors / therapeutic use*
  • Heart Arrest, Induced
  • Male
  • Myocardial Reperfusion Injury / diagnosis
  • Myocardial Reperfusion Injury / diagnostic imaging
  • Myocardial Reperfusion Injury / prevention & control*
  • Protein Kinase C / antagonists & inhibitors*
  • Protein Kinase C / physiology*
  • Sphingosine / analogs & derivatives*
  • Sphingosine / therapeutic use
  • Stroke Volume
  • Time Factors
  • Ventricular Function, Left*

Substances

  • Enzyme Inhibitors
  • Protein Kinase C
  • Sphingosine
  • safingol