Thromboxane A2 receptor-specific antagonism in hypothermic cardiopulmonary bypass.
Using a thromboxane A2 receptor-specific antagonist, SQ 30,741, this study was undertaken to define the role of thromboxane A2 in postischemic myocardial reperfusion injury and in the heparin-protamine reaction. Eighteen heparinized (300 units/kg) sheep were placed on cardiopulmonary bypass (CPB) after complete instrumentation, cooled to 28 degrees C, and had their aortas crossclamped for 1 hour. They were then rewarmed to 36 degrees C and weaned from CPB without inotropic support. Control sheep (n = 6) received a saline infusion throughout the procedure. Bolus animals (n = 6) received 5 mg/kg of SQ 30,741 at 5 minutes after discontinuation of CPB and before protamine sulfate administration. Infusion animals (n = 6) received an SQ 30,741 bolus of 5 mg/kg followed by a continuous infusion of 5 mg.kg-1 hr-1 of SQ 30,741 initiated before CPB. All animals received 5 mg/kg of protamine sulfate over a 15-second period 15 minutes after being weaned from CPB. Control animals exhibited significantly decreased global myocardial function after the 1-hour ischemic interval. Further significant functional decline and increase in pulmonary pressure occurred after protamine sulfate administration. Bolus animals experienced a similar postischemic injury, but had no further decrease in function following protamine infusion. Infusion animals had significantly improved global myocardial function after bypass compared with both other groups and were also protected from the deleterious effects of protamine sulfate administration.(ABSTRACT TRUNCATED AT 250 WORDS)
Mendeloff
E N
EN
Surgery Branch, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD.
Liang
I Y
IY
Swain
J A
JA
Clark
R E
RE
D000818:Animals; D002315:Cardiopulmonary Bypass / Q000009:adverse effects; D003167:Complement Activation; D004353:Drug Evaluation, Preclinical; D004347:Drug Interactions; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D006493:Heparin / Q000494:pharmacology*; D007036:Hypothermia, Induced / Q000009:adverse effects; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D011479:Protamines / Q000009:adverse effects*; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors*; D012756:Sheep; D013928:Thromboxane A2 / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000494:pharmacology
D011479:Protamines; D017482:Receptors, Thromboxane; C054215:SQ 30741; D013928:Thromboxane A2; D006493:Heparin