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A New Platelet-Activating Factor Antagonist (CV-6209) in Preservation of Heart and Lung for Transplantation

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Abstract

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

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Authors and Affiliations

  1. Departments of Surgery, Pathology, and Anaesthesiology, University of British Columbia, Vancouver Hospital and Health Science Centre, and British Columbia Transplant Society, Vancouver, BC, Canada

    Karim A. Qayumi, John C. English, Elizabeth J.E. Feeley, Ahmed Poostizadeh & Maryam Nikbakht-Sangari

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  1. Karim A. Qayumi
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  2. John C. English
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  3. Elizabeth J.E. Feeley
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  4. Ahmed Poostizadeh
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  5. Maryam Nikbakht-Sangari
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Qayumi, K.A., English, J.C., Feeley, E.J. et al. A New Platelet-Activating Factor Antagonist (CV-6209) in Preservation of Heart and Lung for Transplantation. Cardiovasc Drugs Ther 11, 777–785 (1997). https://doi.org/10.1023/A:1007718309177

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