The haemodynamic effects of the thromboxane A2 receptor antagonist GR32191B during cardiopulmonary bypass in the dog.
This study examined whether treatment with the specific thromboxane (TX) A2 receptor antagonist GR32191B would result in an improvement in peripheral haemodynamics during and after cardiopulmonary bypass (CPB) in anaesthetized dogs compared with animals given either saline (control) or aspirin. Following thoracotomy, heparinization and aortic cannulation, and 35 minutes before CPB, dogs received intravenously either GR32191B (15 micrograms/kg/min), saline (50 ml bolus) or aspirin (225 mg bolus) (n = 6 per group). Cardiac output (dye dilution), femoral artery blood flow (electromagnetic flowmeter), gastrocnemius muscle tissue perfusion (133Xe clearance), retinal blood flow (fluorescein angiography), and thromboxane biosynthesis (urinary excretion rates of TXB2 and the metabolite 2,3-dinor-TXB2) were measured before, during and after a standard 90 minute period of CPB at 2.4 l/min/m2 and 28 degrees C. The aspirin-treated group manifested an eightfold reduction in TXB2 excretion compared with controls, indicating a decrease in TXA2 biosynthesis. There were few haemodynamic differences between the groups, though the aspirin-treated group had better maintained muscle tissue perfusion post-CPB and significantly fewer retinal microcirculatory occlusions than GR32191B-treated animals. We conclude that specific TXA2 receptor antagonism provides no significant improvement in peripheral haemodynamics; rather aspirin provides a modest haemodynamic benefit.
Mathie
R T
RT
Department of Surgery, Royal Postgraduate Medical School, London.
Fleming
J S
JS
Barrow
S E
SE
Arnold
J V
JV
Brannan
J J
JJ
Becket
J M
JM
Ritter
J M
JM
Taylor
K M
KM
D000818:Animals; D001713:Biphenyl Compounds / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D002315:Cardiopulmonary Bypass; D004285:Dogs; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006614:Hindlimb; D006868:Hydrolysis; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D009132:Muscles / Q000098:blood supply; D011859:Radiography; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors*; D012171:Retinal Vessels / Q000000981:diagnostic imaging / Q000187:drug effects; D013929:Thromboxane B2 / Q000031:analogs & derivatives / Q000652:urine; D014655:Vascular Resistance / Q000187:drug effects
D001713:Biphenyl Compounds; D006538:Heptanoic Acids; D017482:Receptors, Thromboxane; D013929:Thromboxane B2; C028965:2,3-dinor-thromboxane B2; C060013:vapiprost