A new platelet-activating factor antagonist (CV-6209) in preservation of heart and lung for transplantation.
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.
Qayumi
K A
KA
Department of Surgery, University of British Columbia, Vancouver Hospital, Canada.
English
J C
JC
Feeley
E J
EJ
Poostizadeh
A
A
Nikbakht-Sangari
M
M
D000818:Animals; D005260:Female; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D016027:Heart Transplantation / Q000379:methods* / Q000502:physiology; D008168:Lung / Q000187:drug effects / Q000502:physiology*; D016040:Lung Transplantation / Q000379:methods* / Q000502:physiology; D009926:Organ Preservation / Q000379:methods*; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D011726:Pyridinium Compounds / Q000494:pharmacology*; D015656:Respiratory Mechanics / Q000187:drug effects; D013552:Swine; D014655:Vascular Resistance / Q000187:drug effects
D010972:Platelet Activating Factor; D011726:Pyridinium Compounds; C053321:CV 6209