Preserved coronary endothelial function by inhibition of delta protein kinase C in a porcine acute myocardial infarction model.
BACKGROUND
Previous studies demonstrate impairment of endothelial-dependent vasodilation after ischemia/reperfusion (I/R). Though we have demonstrated that inhibition of delta protein kinase C (delta PKC) at reperfusion reduces myocyte damage and improves cardiac function in a porcine acute myocardial infarction (AMI) model, impact of the selective delta PKC inhibitor on epicardial coronary endothelial function remains unknown.


METHODS
Either delta PKC inhibitor (delta V1-1, n=5) or saline (n=5) was infused into the left anterior descending artery at the last 1 min of the 30-min ischemia by balloon occlusion. In vivo responses to bradykinin (endothelium-dependent vasodilator) or nitroglycerin (endothelium-independent vasodilator) were analyzed at 24 h after I/R using intravascular ultrasound. Vascular responses were calculated as the ratio of vessel area at each time point (30, 60, 90 and 120 s after the infusion), divided by values at baseline (before the infusion).


RESULTS
In control pigs, endothelial-dependent vasodilation following bradykinin infusion in infarct-related epicardial coronary artery was impaired, whereas in delta PKC inhibitor-treated pigs the endothelial-dependent vasodilation was preserved. Nitroglycerin infusion caused similar vasodilatory responses in the both groups.


CONCLUSIONS
This is the first demonstration that a delta PKC inhibitor preserves vasodilator capacity in epicardial coronary arteries in an in vivo porcine AMI model. Because endothelial dysfunction correlates with worse outcome in patients with AMI, this preserved endothelial function in epicardial coronary arteries might result in a better clinical outcome.
Kaneda
Hideaki
H
Ikeno
Fumiaki
F
Inagaki
Koichi
K
Mochly-Rosen
Daria
D
D000818:Animals; D003331:Coronary Vessels; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000503:physiopathology*; D008955:Models, Cardiovascular; D009203:Myocardial Infarction / Q000503:physiopathology*; D032383:Myocytes, Cardiac / Q000502:physiology; D051745:Protein Kinase C-delta / Q000037:antagonists & inhibitors*; D013552:Swine; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
D051745:Protein Kinase C-delta