No prevention of ischemic preconditioning by the protein kinase C inhibitor staurosporine in swine.
The delay of infarct size development by ischemic preconditioning involves the activation of protein kinase C in rats and rabbits. In dogs the role of protein kinase C in ischemic preconditioning is controversial. We investigated whether or not the activation of protein kinase C is a prerequisite for ischemic preconditioning in swine. Swine were used, since they are large mammals and since infarct development in this species, due to the lack of an innate collateral circulation, is similar to that in humans. In 20 enflurane-anesthetized swine, the proximal left anterior descending coronary artery was cannulated and perfused from an extracorporeal circuit. The impact of continuous intracoronary infusion of 10(-7) mol/L staurosporine, a potent protein kinase C inhibitor, on global and regional myocardial function (sonomicrometry), subendocardial blood flow (ENDO, microspheres), and infarct size (IS, triphenyltetrazolium chloride staining after 120 minutes of reperfusion) was analyzed. Staurosporine (10(-7) mol/L) abolished the 1.6-fold increase in coronary arterial resistance in response to 10(-6) mol/L IC 4 beta-phorbol 12-myristate 13-acetate, a potent protein kinase C activator. In the presence of staurosporine, 90 minutes of low-flow ischemia at an ENDO of 0.05 +/- 0.04 (mean +/- SD) mL.min-1.g-1 resulted in an IS of 12.5 +/- 8.6% (n = 10) of the area at risk. Also, in the presence of staurosporine, ischemic preconditioning by a cycle of 10 minutes of low-flow ischemia followed by 15 minutes reperfusion before the 90 minutes sustained ischemic period (ENDO, 0.05 +/- 0.03 mL.min-1.g-1) reduced IS to 3.3 +/- 3.4% (n = 10, P < .05). The protein kinase C inhibitor staurosporine does not prevent ischemic preconditioning in swine.
Vahlhaus
C
C
Abteilung für Pathophysiologie, Universitätsklinikum Essen Germany.
Schulz
R
R
Post
H
H
Onallah
R
R
Heusch
G
G
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D003326:Coronary Circulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006321:Heart / Q000503:physiopathology; D006439:Hemodynamics; D009203:Myocardial Infarction / Q000473:pathology; D017202:Myocardial Ischemia / Q000503:physiopathology*; D015425:Myocardial Reperfusion; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D019311:Staurosporine; D013552:Swine; D013556:Swine, Miniature
D000470:Alkaloids; D004791:Enzyme Inhibitors; D011493:Protein Kinase C; D019311:Staurosporine