Myocardial function following cold ischemic storage is improved by cardiac-specific overexpression of A1-adenosine receptors.
Cold ischemic storage of hearts for transplantation is limited to 4-6 h, and therefore the development of strategies to extend preservation time may increase the donor pool of hearts. Overexpression of A1-adenosine receptors (A1AR) can protect hearts from acute ischemic injury, and the purpose of this study was to test the hypothesis that overexpression of A1AR will improve tolerance to longer periods of cold ischemic preservation. Hearts from 18 wild type and 16 transgenic mice with overexpression of A1AR (A1AR Trans) were isolated and perfused, and then subjected to 18 h of preservation in 5 degrees C University of Wisconsin solution followed by 2 h of reperfusion. Left ventricular end diastolic pressure and left ventricular developed pressure were measured as indices of ventricular function. Cell viability was assessed by determination of infarct size and myocardial cell apoptosis. A1AR Trans hearts showed improved function following 18 h of ischemia, as shown by lower end diastolic pressure (p < 0.05) and higher recovery of left ventricular developed pressure (p < 0.05) during reperfusion. A1AR Trans hearts had markedly reduced infarct size (p < 0.05) and decreased apoptosis (p < 0.05). Overexpression of cardiac A1AR imparts cardioprotection during long-term cold ischemic preservation.
Crawford
Marguerite
M
Department of Pediatrics, Division of Cardiology, Cardiovascular Research Center, University of Virginia, Charlottesville, Virginia 22908, USA.
Ford
Sara
S
Henry
Michele
M
Matherne
G Paul
GP
Lankford
Amy
A
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D003080:Cold Temperature; D006321:Heart / Q000502:physiology* / Q000503:physiopathology; D006339:Heart Rate / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D009336:Necrosis; D009926:Organ Preservation / Q000379:methods*; D043682:Receptor, Adenosine A1 / Q000096:biosynthesis* / Q000235:genetics; D013997:Time Factors; D016277:Ventricular Function, Left / Q000502:physiology
D043682:Receptor, Adenosine A1