POTENTIATION OF THE ANTI-THROMBOTIC EFFECT OF PROSTACYCLIN BY SIMULTANEOUS ADMINISTRATION OF AMINOPHYLLINE IN A CANINE MODEL OF CORONARY-ARTERY THROMBOSIS

  • 1 January 1983
    • journal article
    • research article
    • Vol. 227  (2) , 288-294
Abstract
The antithrombotic efficacy of prostacyclin (PG[prostaglandin]I2) 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 per min) into the left atrial appendage and aminophylline (20 .mu.g/kg per 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-h stimulation period. Every animal in the control (Tris buffer plus ethylene diamine, n = 7), PGI2 (25 ng/kg per min) only (n = 6) and aminophylline only (n = 7) groups developed completely occlusive coronary artery thrombi. None of the animals receiving PGI2 (25 ng/kg per min) plus aminophylline or PGI2 (50 ng/kg per min) plus aminophylline underwent occlusive thrombus formation. The average thrombus mass developed in response to intimal injury of the LXC coronary artery was 57 .+-. 14 mg (mean) in the control group. Aminophylline administration in conjunction with PGI2 infusion at doses of 25 and 50 ng/kg per min significantly reduced thrombus mass to 11 .+-. 2 and 10 .+-. 1 mg, respectively (P < 0.05). PGI2 (25 ng/kg per min) plus aminophylline reduced mean arterial pressure by 12% from 116 .+-. 5 to 102 .+-. 4 mm Hg. Evidently the combined administration of aminophylline with low-dose PGI2 provides antithrombotic efficacy with minimizing the detrimental hemodynamic effects of large-dose PGI2 administration.