A new platelet-activating factor antagonist (CV-6209) in preservation of heart and lung for transplantation.

Abstract

The objective of this experimental protocol was to evaluate the protective effect of a new, potent platelet-activating factor (PAF) antagonist CV-6209 and the use of this compound in combination with allopurinol on ischemia-reperfusion injury in a swine model of heart-lung transplantation. Forty-two swine were divided into three groups, with seven donors and seven recipients in each. In group A, the PAF antagonist CV-6209 was administered in a single dosage of 1 mg/kg by slow intravenous injection at 1 hour before crossclamping of the aorta in both donors and recipients. In group B the combination of allopurinol and the PAF antagonist CV-6209 was used. Allopurinol was administered as a pretreatment regime of 50 mg/kg/day for 3 days prior to ischemia. The PAF antagonist dosage and regime of administration were the same as in group A, and both donors and recipients were pretreated with this combination. Group C was the control in which heart-lung transplantations were performed without interventional therapies. Based on the comparison of pre- and post-transplantation assessments of cardiac and pulmonary functional integrity within groups, and post-transplantation among groups, animals in groups A and B were significantly (P < 0.05) better protected from ischemia-reperfusion injury than animals in group C. The difference between groups A and B, however, was insignificant at all times. Morphological findings are in agreement with measures of physiological variation among experimental groups. It is suggested that the new PAF antagonist CV-6209 is effective in the prevention of heart and lung ischemia-reperfusion injury with and without allopurinol pretreatment.