Objective: To evaluate the role of platelet-activating factor antagonism (PAFA) and mechanical neutrophil depletion with leukocyte depleting filters for control of ischemia-reperfusion injury in corrective surgery for cyanotic heart disease.

Methods: A swine model of cyanotic heart disease was evaluated with three study groups; 1) control, 2) PAFA and 3) leukocyte depleting filters. The cyanotic model was created by left atrial appendage and pulmonary artery fistula and distal (to the fistula) pulmonary artery banding in the weanling stage. The fistula shunt was performed under general anesthesia (maintained with isoflurane) through left thoracotomy approach. The shunt was approximately 4 mm by 6 mm. The experimental procedure was performed after 5 weeks to 7 weeks with body weight >20 kg and oxygen saturation 80±5%. Corrective surgery was performed through median sternotomy on cardiopulmonary bypass with repair of the shunt. Myocardial preservation was afforded by 4:1 blood cardioplegia delivered antegrade at 8°C. The total ischemic time was 90 minutes. The PAFA-CV6209 was delivered IV 10 min before cross-clamping. The leukocyte depleting Pall filters on CPB were utilized in the second group. Ten and 30 minute post-CPB hemodynamics were performed with impedance ventriculography assessed.

Results: There are 4 deaths in the control group within 30 min post-bypass; treated groups all survived over 60 min (p<0.05). Significant dopamine was required in the control group vs leukocyte-depleting filter and PAFA groups (46.6+43.7 vs 6.5+7.8 and 11.0+9.0)(mean + STD)(p<0.05). Ventricular performance assessment revealed Emax was significantly superior in the leukocyte-depleting filter group at 10 and 30 min post-bypass vs control group.

Conclusions: Leukocyte-depleting filters and platelet- activating factor antagonism both provide myocardial protection while leukocyte-depleting filter provides superior postoperative myocardial contractility.