title: Pre-clamp cardioprotection by protein kinase C (PKC) inhibitor improves left ventricular function following canine normothermic arrest.
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%.
authors.affiliation: St. Luke's-Roosevelt Hospital Center at Columbia University, College of Physicians and Surgeons, New York, New York, USA.
authors.forename: C E
authors.initials: CE
authors.lastname: Anagnostopoulos
authors.forename: C P
authors.initials: CP
authors.lastname: Connery
authors.forename: H
authors.initials: H
authors.lastname: Dumont
authors.forename: Z
authors.initials: Z
authors.lastname: Hillel
authors.forename: W
authors.initials: W
authors.lastname: Herring
authors.forename: L
authors.initials: L
authors.lastname: Adams
authors.forename: G W
authors.initials: GW
authors.lastname: Davis
mesh_terms: D000818:Animals; D002315:Cardiopulmonary Bypass; D004285:Dogs; D004311:Double-Blind Method; D004452:Echocardiography; D004562:Electrocardiography; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D006324:Heart Arrest, Induced; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000175:diagnosis / Q000000981:diagnostic imaging / Q000517:prevention & control*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors* / Q000502:physiology*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013318:Stroke Volume; D013997:Time Factors; D016277:Ventricular Function, Left
chemical_list: D004791:Enzyme Inhibitors; D011493:Protein Kinase C; D013110:Sphingosine; C005682:safingol