Mechanisms of coronary vasomotor dysfunction in the transplanted heart.
The transplanted heart sustains both cold ischemic and reperfusion injuries. These can produce coronary vascular endothelial or smooth muscle injury or both, which, in turn, can produce coronary vasomotor dysfunction. Using a canine model of autologous heart transplantation, we examined the following coronary vasomotor control mechanisms in isolated coronary artery rings: (1) endothelial-dependent cyclic guanosine monophosphate (cGMP)-mediated vasorelaxation (response to acetylcholine); (2) endothelial-independent cGMP-mediated vasorelaxation (response to sodium nitroprusside); and (3) beta-adrenergic cyclic adenosine monophosphate (cAMP)-mediated vasorelaxation (response to isoproterenol hydrochloride). Further, these mechanisms were related to 3 hours of cold ischemia alone and to 3 hours of cold ischemia plus 1 hour of reperfusion. Autologous heart transplantation was performed in dogs, and isolated distal left anterior descending coronary artery rings were studied in individual organ chambers. Cold ischemia alone produced significant dysfunction of beta-adrenergic cAMP-mediated vasorelaxation, which was exacerbated after reperfusion. Neither endothelial-dependent nor endothelial-independent cGMP-mediated vasorelaxation was dysfunctional after cold ischemia alone, but both were significantly impaired after reperfusion. We conclude that cold ischemia and reperfusion each produce coronary vasomotor dysfunction in the transplanted heart. Cumulatively, such coronary vasomotor dysfunction can acutely impair coronary vasodilatation and potentially jeopardize myocardial blood flow in the transplanted heart.
Department of Surgery, University of Colorado Health Sciences Center, Denver 80262.
D A
DA
Fullerton
M B
MB
Mitchell
R C
RC
McIntyre
J M
JM
Brown
X
X
Meng
D N
DN
Campbell
F L
FL
Grover
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D003080:Cold Temperature; D003331:Coronary Vessels / Q000187:drug effects / Q000503:physiopathology*; D000242:Cyclic AMP / Q000502:physiology; D006152:Cyclic GMP / Q000502:physiology; D004285:Dogs; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology; D005260:Female; D016027:Heart Transplantation / Q000502:physiology*; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology*; D009599:Nitroprusside / Q000494:pharmacology; D014666:Vasomotor System / Q000187:drug effects / Q000503:physiopathology*
D009599:Nitroprusside; D000242:Cyclic AMP; D006152:Cyclic GMP; D007545:Isoproterenol; D000109:Acetylcholine