Thromboxane synthetase inhibition reduces ventricular irritability after coronary occlusion and reperfusion.
Reperfusion of ischemic tissue is responsible for production of metabolites with deleterious local vascular effects. Thromboxane A2, a potent vasoconstrictor and platelet aggregator, has been implicated as a mediator of the "reperfusion injury." We studied the effect of an experimental thromboxane synthetase inhibitor, OKY-046, on coronary sinus thromboxane levels, ventricular irritability, myocardial contractility, infarct salvage, and histologic features of reperfusion. Sixteen sheep were randomized to OKY-046, 3 mg/kg, or saline vehicle before 3-hour occlusion and subsequent reperfusion of the left anterior descending artery. The OKY group demonstrated less ventricular irritability as measured by incidence of ventricular fibrillation and necessity for countershock to reverse tachyarrhythmias. Coronary sinus thromboxane levels were significantly lower in the OKY group compared with the control group. There is additional evidence to suggest that OKY increases infarct salvage and attenuates histologic features of microcirculatory damage.
Austin
J C
JC
Department of Surgery, Harvard Medical School, Boston, MA.
Berrizbeitia
L D
LD
Schoen
F J
FJ
Kauffman
R P
RP
Hechtman
H B
HB
Cohn
L H
LH
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000179:Acrylates / Q000494:pharmacology*; D000818:Animals; D003326:Coronary Circulation; D003327:Coronary Disease / Q000188:drug therapy / Q000201:enzymology*; D004195:Disease Models, Animal; D008689:Methacrylates / Q000494:pharmacology* / Q000627:therapeutic use; D008833:Microcirculation / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects*; D011897:Random Allocation; D012756:Sheep; D013929:Thromboxane B2 / Q000097:blood; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*; D014693:Ventricular Fibrillation / Q000201:enzymology / Q000517:prevention & control*
D000179:Acrylates; D008689:Methacrylates; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D013930:Thromboxane-A Synthase; C034364:ozagrel