Effects of indomethacin on systemic and coronary hemodynamics in patients with coronary artery disease.
The effects and possible mechanisms of actions of indomethacin on systemic and coronary hemodynamics were studied in 17 patients with coronary artery disease. Group I patients (12) were given either indomethacin or placebo in the absence of prior cyclooxygenase inhibition and group II (five) were given indomethacin after prior treatment with 2600 mg of aspirin. In group I, systolic blood pressure rose from a baseline of 136 +/- 5 mm Hg to a peak level of 158 +/- 8 mm Hg 5 minutes after drug (p less than 0.01). This was associated with a fall in coronary blood flow and a rise in coronary vascular resistance from a baseline of 1.36 +/- 0.4 mm Hg/ml/min to 1.99 +/- 0.7 mm Hg/ml/min 5 minutes after indomethacin (p less than 0.01). Immunoreactive thromboxane B2 levels fell from 191 to 1.4 ng/ml. No changes were noted in plasma renin activity, angiotensin II, or catecholamine levels. Immunoreactive thromboxane B2 levels were undetectable throughout the study period in group II patients and the blood pressure response to indomethacin was attenuated. Baseline coronary blood flow was significantly higher (p less than 0.01) and baseline coronary vascular resistance significantly lower (p less than 0.01) than in group I. At all time points after indomethacin, the fall in coronary blood flow was greater and the increase in coronary vascular resistance less in group II versus group I (p less than 0.001). These findings suggest a dissociation between the effect of indomethacin on systemic and coronary hemodynamics, the former apparently being more prostaglandin-dependent than the latter.
D000328:Adult; D001241:Aspirin / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects*; D003327:Coronary Disease / Q000503:physiopathology*; D016861:Cyclooxygenase Inhibitors; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D011453:Prostaglandins / Q000502:physiology; D014655:Vascular Resistance / Q000187:drug effects
D016861:Cyclooxygenase Inhibitors; D011453:Prostaglandins; D001241:Aspirin; D007213:Indomethacin