Coronary vasoconstrictor effect of indomethacin in patients with coronary-artery disease.
Prostaglandins may be important regulators of coronary blood flow. To investigate this possibility, we studied the effect of blockade of prostaglandin synthesis by indomethacin in nine patients with coronary-artery disease. Coronary-sinus blood flow (determined with the thermodilution technique) was recorded, together with mean arterial blood pressure and the myocardial arteriovenous oxygen difference from simultaneously obtained arterial and coronary-sinus blood samples, before and 20 minutes after an intravenous dose of indomethacin (0.5 mg per kilogram of body weight). There were significant increases (P less than 0.05) in mean arterial pressure (from 99 +/- 4 to 118 +/- 5 mm Hg [+/- S.E.M.]), coronary vascular resistance (+73 per cent), and myocardial arteriovenous oxygen difference (from 107 +/- 5 to 138 +/- 4 ml per liter) after indomethacin, but coronary blood flow fell significantly, from 181 +/- 29 to 111 +/- 14 ml per minute (P less than 0.05). Thus, despite an increase in myocardial oxygen demand, coronary blood flow fell and coronary vascular resistance increased. This coronary vasoconstrictor effect may have been due to blockade of vasodilatory prostaglandin synthesis or to a direct drug effect. Whatever the mechanism, indomethacin should be used with caution in patients with severe coronary-artery disease.
D001794:Blood Pressure / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects; D003327:Coronary Disease / Q000378:metabolism / Q000503:physiopathology*; D003331:Coronary Vessels / Q000187:drug effects*; D006801:Humans; D007213:Indomethacin / Q000009:adverse effects* / Q000494:pharmacology; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism; D010100:Oxygen / Q000097:blood; D010101:Oxygen Consumption; D011453:Prostaglandins / Q000096:biosynthesis; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects*
D011453:Prostaglandins; D010100:Oxygen; D007213:Indomethacin