In the present study we have investigated the effect of Amrinone on the hemodynamics, platelet counts, prostacyclin and thromboxane synthesis and platelet function. Results show that infusion of the drug increased the heart rate and lowered left atrial, aortic and pulmonary artery pressures within five minutes after a single bolus injection of 2 mg/kg IV dose. Platelet counts made from the blood obtained from anesthetized dogs after the drug infusion showed severe loss of platelets. However, infusion of a similar dose in awake dogs showed no such detrimental effect on platelets. Examination of formalin fixed blood for aggregates showed no more clumps in the treated samples than in the control. Platelets obtained from canine blood drawn at 30 minutes post infusion of the drug showed no aggregatory response to arachidonate. However, the response of these platelets to ADP was quite normal. Amrinone infusion had no inhibitory effect on the ability of vascular tissue to convert arachidonic acid to prostacyclin. Similarly, no inhibitory action could be observed on platelet cyclo-oxygenase activity at this concentration (2 mg/kg). In vitro studies on human platelets showed significant inhibition of cyclo-oxygenase at high concentrations (0.5 mg/ml). Therefore it is unlikely that the drug caused inhibition of the platelet response to arachidonate by the inhibition of prostaglandin synthesis during infusion, as the dose used was quite low (2 mg/kg) compared to what is required for the inhibition of cyclo-oxygenase.
Bibliographical noteFunding Information:
This work was supported by USPHS grants HL-18204, HL-II880, AM-06317, HL-06314, CA-12607, CA-08832, CA-I1996, GM-AM-22167, HL-20695, HL-16833, AM-15317 and a grant from the Leukemia Task Force. The authors wish to thank Mrs. Linda A. Leis and Dr. K.R. Reddy for their technical assistance.