Comparison of new iron chelating agents in the prevention of ischemia/reperfusion injury: a swine model of heart-lung transplantation.
The preservation of the heart and lung for transplantation remains a major concern in extended ischemic intervals. This experimental endeavor evaluates and compares the efficacy of iron chelating agents such as high molecular weight deferoxamine and 21-aminosteroid (U74006F) in a swine model of heart-lung transplantation. Heat-lung blocks were exposed to 4 h and 45 min of ischemia and 2 h of reperfusion. Animals were divided into three groups. Group A was a control without pharmacological intervention. In groups B and C, 21-aminosteroid (U74006F), 10 mg/kg, and high molecular weight deferoxamine, 50 mg/kg, were used, respectively. The results of functional parameters (cardiac index, stroke index, lung water, PO2, PCO2, alveolar-arterial gradient, and alveolar-arterial ratio) demonstrated superior heart and lung function for group C, where high molecular weight deferoxamine was used. Alterations of heart and lung function were significantly more (p less than .001) for control animals and for group B where U74006F was used. This study suggests that formation of hydroxyl radicals was affected by chelation of iron with high molecular weight deferoxamine, which reflects better heart and lung function and consequently less damage to this group of animals. The compound 21-aminosteroid U74006F failed to protect the heart and lung from ischemic-reperfusion injury in this model of heart-lung transplantation.
Qayumi
A K
AK
Department of Surgery, University of British Columbia, Vancouver, Canada.
Jamieson
W R
WR
Poostizadeh
A
A
Germann
E
E
Gillespie
K D
KD
D000818:Animals; D002614:Chelating Agents / Q000494:pharmacology*; D003676:Deferoxamine / Q000494:pharmacology; D005260:Female; D016041:Heart-Lung Transplantation / Q000009:adverse effects* / Q000502:physiology; D006878:Hydroxides / Q000378:metabolism; D017665:Hydroxyl Radical; D007501:Iron / Q000378:metabolism; D008054:Lipid Peroxides / Q000037:antagonists & inhibitors; D008168:Lung / Q000503:physiopathology; D055370:Lung Injury; D008954:Models, Biological; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control; D011281:Pregnatrienes / Q000494:pharmacology; D015427:Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control*; D013552:Swine
D002614:Chelating Agents; D006878:Hydroxides; D008054:Lipid Peroxides; D011281:Pregnatrienes; D017665:Hydroxyl Radical; D007501:Iron; D003676:Deferoxamine; C053355:tirilazad