Improved donor myocardial recovery with a new lazaroid lipid antiperoxidant in the isolated canine heart.
U74006F is a new 21-amino steroid (lazaroid) that prevents lipid peroxidation without glucocorticoid or mineralocorticoid side effects. Reperfusion injury has been reduced by the addition of various free radical scavengers and antiperoxidants to the reperfusate. To assess the effect of U74006F on reperfusion of donor hearts subjected to prolonged hypothermic ischemia, 21 isolated canine hearts were divided into three groups: control (group 1), drug (2 mg/kg) injected into the oxygenated blood perfusate immediately before 4 hours of preservation (group 2), and drug (2 mg/kg) injected 1 hour before heart isolation and again 15 minutes before reperfusion (group 3). After control left ventricular function studies (with an intraventricular balloon) and biopsy for high-energy phosphates and dry/wet ratios, the hearts were arrested with cold cardioplegia and cooled for 4 hours then reperfused for 3 hours. Left ventricular work was calculated by systolic and diastolic pressure curves, which showed a better return of function in group 3 hearts (1625, 2150, and 3493 mm Hg/ml in groups 1, 2, and 3, respectively, at 180 minutes of reperfusion; p = 0.02). This was likely the result of improved diastolic compliance in group 3. Dry/wet ratios showed increased tissue edema in all hearts at the end of reperfusion. Although high-energy phosphate concentrations were not different between groups, adenosine was best preserved in group 3 (p = 0.03), suggesting reduced washout of this precursor. In conclusion, administration of U74006F before preservation and reperfusion may be useful for donor heart protection.
Hendry
P J
PJ
Department of Surgery, Duke University Medical Center, Durham, N.C. 27710.
Anstadt
M P
MP
Plunkett
M D
MD
Amato
M T
MT
Menius
J A
JA
Lowe
J E
JE
D000227:Adenine Nucleotides / Q000378:metabolism; D000818:Animals; D002314:Cardioplegic Solutions; D004285:Dogs; D006321:Heart / Q000187:drug effects*; D016027:Heart Transplantation / Q000502:physiology*; D008054:Lipid Peroxides / Q000037:antagonists & inhibitors*; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism; D009926:Organ Preservation / Q000379:methods; D011281:Pregnatrienes / Q000494:pharmacology*; D013997:Time Factors; D016277:Ventricular Function, Left / Q000187:drug effects
D000227:Adenine Nucleotides; D002314:Cardioplegic Solutions; D008054:Lipid Peroxides; D011281:Pregnatrienes; C053355:tirilazad