Effects of platelet-activating factor antagonist CV-3988 in preservation of heart and lung for transplantation.
The preservation of heart and lung for transplantation remains a major concern in extended ischemic intervals. This experiment evaluated the effect of high molecular weight deferoxamine and a platelet-activating factor antagonist (CV-3988) in ischemic reperfused tissue. Heart-lung transplantation was performed in a swine model after 4 hours 45 minutes of ischemia. Animals were divided into three groups. Group A was a control without pharmacological intervention. In group B, high molecular weight deferoxamine, 50 mg/kg, was used, and in group C, platelet-activating factor antagonist CV-3988, 10 mg/kg, was used. The results of functional variables (cardiac index, stroke index, lung water, oxygen and carbon dioxide tensions, alveolar-arterial gradient, and alveolar-arterial ratio) demonstrated superior heart and lung function for groups B and C compared with the control group. These alterations of heart and lung function were significantly less (p less than 0.001) in group C, in which the platelet-activating factor antagonist (CV-3988) was used. The study revealed that formation of hydroxyl radicals and platelet-activating factor play an important role in the pathogenesis of ischemia reperfusion injury. Prevention of hydroxyl radical formation with high molecular weight deferoxamine and inactivation of platelet-activating factor with CV-3988 reduce the ischemia-reperfusion injury significantly.
Department of Surgery, University of British Columbia, Vancouver, Canada.
A K
AK
Qayumi
W R
WR
Jamieson
A
A
Poostizadeh
D000818:Animals; D002245:Carbon Dioxide / Q000097:blood; D003676:Deferoxamine; D015633:Extravascular Lung Water / Q000378:metabolism; D005260:Female; D016041:Heart-Lung Transplantation; D006439:Hemodynamics / Q000187:drug effects; D009926:Organ Preservation; D010100:Oxygen / Q000097:blood; D010742:Phospholipid Ethers; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D012119:Respiration; D013552:Swine
D010742:Phospholipid Ethers; D010972:Platelet Activating Factor; D002245:Carbon Dioxide; C037913:CV 3988; D003676:Deferoxamine; D010100:Oxygen