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  • Title: Endothelium-dependent vasodilation during acute rejection in dogs.
    Author: Pearson PJ, Wei CM, Lin PJ, Burnett JC, Cable DG, Hamner CE, Schaff HV.
    Journal: J Surg Res; 2004 Sep; 121(1):56-61. PubMed ID: 15313376.
    Abstract:
    BACKGROUND: Acute rejection, which is a major cause of death after cardiac transplantation, is associated with increased coronary artery resistance and decreased coronary blood flow, leading to congestive heart failure. MATERIALS AND METHODS: To examine the contribution of endothelium-derived vasoactive factors on coronary artery tone during acute rejection, dogs underwent orthotopic heart transplantation without immunosuppression. Plasma levels of endothelin, a potent endogenous vasoconstrictor peptide, and atrial natriuretic peptide, an endogenous coronary vasodilator of cardiac origin, were measured daily by radioimmunoassay until sacrifice. RESULTS: Over 7 days, all animals developed acute rejection accompanied by progressive increases in plasma endothelin (10 +/- 3 to 25 +/- 4 pg/ml, n = 6, P < 0.05) and atrial natriuretic peptide (57 +/- 10 to 188 +/- 42 pg/ml, n = 6, P < 0.05). However, in organ chamber experiments, coronary artery segments from rejecting hearts exhibited normal endothelium-dependent vasodilation to acetylcholine, adenosine diphosphate, and the calcium ionophore A23187. In addition, coronary arteries exhibited normal relaxation to sodium nitroprusside (cyclic guanosine monophosphate-dependent) and isoproterenol (cyclic adenosine monophosphate-dependent). CONCLUSIONS: In early, untreated acute rejection after orthotopic heart transplantation, graft dysfunction is not associated with impaired endothelium-dependent coronary artery vasodilation but may result from enhanced production of endothelin, a potent vasoconstrictor.
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