Potentiation of the antithrombotic effect of prostacyclin by simultaneous administration of aminophylline in a canine model of coronary artery thrombosis.
The antithrombotic efficacy of prostacyclin (PGI2) when administered in conjunction with the phosphodiesterase inhibitor aminophylline was evaluated in a canine model in which coronary artery thrombosis was induced by electrical stimulation of the intimal surface of the left circumflex (LCX) coronary artery. Infusions of PGI2 (25 or 50 ng/kg/min) into the left atrial appendage and aminophylline (20 micrograms/kg/min) or ethylene diamine into the left jugular vein were initiated 10 min before the start of LCX coronary artery stimulation and continued for the 6-hr stimulation period. Every animal in the control (Tris buffer plus ethylene diamine, n = 7), PGI2 (25 ng/kg/min) only (n = 6) and aminophylline only (n = 7) groups developed completely occlusive coronary artery thrombi. In contrast, none of the animals receiving PGI2 (25 ng/kg/min) plus aminophylline or PGI2 (50 ng/kg/min) plus aminophylline underwent occlusive thrombus formation. The average thrombus mass developed in response to intimal injury of the LCX coronary artery was 57 +/- 14 mg (X +/- S.E.M.) in the control group. Aminophylline administration in conjunction with PGI2 infusion at doses of 25 and 50 ng/kg/min significantly reduced thrombus mass to 11 +/- 2 and 10 +/- 1 mg, respectively (P less than .05). PGI2 (25 ng/kg/min) plus aminophylline reduced mean arterial pressure by 12% from 116 +/- 5 to 102 +/- 4 mm Hg. These data demonstrate that the combined administration of aminophylline with low-dose PGI2 provides antithrombotic efficacy while minimizing the detrimental hemodynamic effects of large-dose PGI2 administration.
D000628:Aminophylline / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003327:Coronary Disease / Q000188:drug therapy* / Q000209:etiology; D000242:Cyclic AMP / Q000378:metabolism; D004285:Dogs; D004357:Drug Synergism; D011464:Epoprostenol / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D013806:Theophylline / Q000097:blood
D000628:Aminophylline; D013806:Theophylline; D011464:Epoprostenol; D000242:Cyclic AMP