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.