Cardiac allograft preservation using donor-shed blood supplemented with L-arginine.
BACKGROUND
Despite improved preservation techniques, myocardial and endothelial dysfunction persists after cardiac transplantation. L-arginine has been shown to decrease endothelial injury in several models of ischemia and reperfusion. We assessed the effects of L-arginine on allograft preservation in a porcine model of cardiac transplantation.


METHODS
Orthotopic cardiac transplants were performed in Yorkshire pigs. Hearts were randomly arrested with high potassium cardioplegia with or without L-arginine at a dose of 2.5 mmol/liter (LARGlow) and 5.0 mmol/liter. Donor-shed blood was collected at the time of organ harvest and intermittently perfused throughout the storage period. Coronary endothelial function was assessed at baseline and after reperfusion by measuring the change in coronary blood flow after exposure to acetylcholine or nitroglycerin. Pressure-volume relationships before and after transplant were evaluated with conductance catheter measurements. Myocardial biopsy specimens were assessed for inflammatory markers of cellular injury.


RESULTS
High-dose L-arginine uniformly resulted in ischemic contracture in all hearts, and there was no return of function in any hearts after storage. The low-dose L-arginine group had a greater ability to wean off cardiopulmonary bypass and displayed improved recovery of left ventricular function. Control animals had a 26% reduction in coronary flow compared with 13% for LARGlow. LARGlow resulted in decreased release of inflammatory cytokines compared with control.


CONCLUSIONS
Low-dose L-arginine preserves myocardial and endothelial function and decreases endothelial injury when it is used as a supplement to intermittent donor blood perfusion. In contrast, high-dose L-arginine resulted in severe endothelial injury and an inability to recover ventricular function after 5 hours of global ischemia.
Ramzy
Danny
D
Division of Cardiac Surgery, University of Toronto, Toronto General Hospital, Toronto, Ontario, Canada.
Rao
Vivek
V
Mallidi
Hari
H
Tumiati
Laura C
LC
Xu
Ning
N
Miriuka
Santiago
S
Feindel
Christopher M
CM
D000818:Animals; D001120:Arginine / Q000008:administration & dosage; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D001804:Blood Transfusion, Autologous; D015815:Cell Adhesion Molecules / Q000097:blood; D003331:Coronary Vessels; D004730:Endothelium, Vascular / Q000276:immunology; D016027:Heart Transplantation; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood; D023421:Models, Animal; D009206:Myocardium / Q000473:pathology; D009926:Organ Preservation / Q000379:methods*; D018384:Oxidative Stress / Q000276:immunology; D010477:Perfusion / Q000379:methods*; D020127:Recovery of Function; D013552:Swine; D014184:Transplantation, Homologous / Q000276:immunology; D014652:Vascular Diseases / Q000276:immunology; D014666:Vasomotor System / Q000276:immunology; D016277:Ventricular Function, Left / Q000276:immunology
D015415:Biomarkers; D015815:Cell Adhesion Molecules; D036341:Intercellular Signaling Peptides and Proteins; D001120:Arginine