Amelioration of the deleterious effects of platelets activated during cardiopulmonary bypass. Comparison of a thromboxane synthetase inhibitor and a prostacyclin analogue.

ABSTRACT

Thrombocytopenia and platelet dysfunction are commonly seen after cardiopulmonary bypass. In addition, the microvascular bed of ischemic myocardium is a potent stimulus for platelet deposition and microvascular plugging. Thus, it would appear theoretically advantageous to provide pharmacologic protection of platelets by inhibiting their response to activating agents and thereby preventing their loss into the extracorporeal circuit; this would further inhibit myocardial platelet deposition and the deleterious effects therein. Twenty-one mongrel dogs were placed on cardiopulmonary bypass with 30 minutes of normothermic global ischemia. They were randomly assigned to receive pretreatment with an infusion of saline (control, n = 8), a thromboxane synthetase inhibitor (RO-22-4679, n = 5), or a prostacyclin analogue that does not produce hypotension (ZK 36,374, n = 8). The platelet count in those animals treated with ZK 36,374 was significantly higher at the end of the experiment than in the control group (102.8 +/- 10.7 X 10(3) versus 69.7 +/- 10.6 X 10(3), p less than 0.01); the animals treated with RO-22-4679 had a platelet count between the other two groups (92.8 +/- 14.8 X 10(30)), which was not significantly different from either. Myocardial platelet deposition was measured with indium 111-labeled platelets. Those animals treated with ZK 36,374 had a much lower level of platelet deposition than the group of controls; again the RO-22-4679 group had values between the other two. Finally, myocardial blood flow after global ischemia and cardiopulmonary bypass, measured with radioactive microspheres, was significantly higher in the ZK 36,374 group than in the control group. We conclude that ZK 36,374 prevents platelet consumption during cardiopulmonary bypass over and above that seen with inhibition of thromboxane synthesis alone. It also prevents deposition of platelets into the myocardium after global ischemia and we presume by that mechanism increases myocardial blood flow.