Cardiac transplantation and resistance artery myogenic tone.
Transplantation is an effective treatment for end-stage heart disease; however, most grafts eventually fail by progressive cardiac failure. Primarily, failure is ischemic due to the occlusive nature of transplant vascular disease (TVD). Early after transplantation and preceding TVD, alterations in coronary physiology such as reduced vascular myogenic tone occur. Resistance arteries possess an inherent ability to constrict in response to transmural pressure; this constrictive response (myogenic tone) is important in fluid homeostasis. Recent evidence suggests that a decline in myogenic tone leads to deficits in cardiac contractility. Factors that reduce myogenic tone in transplantation include constitutive nitric oxide synthase and inducible nitric oxide synthase catalyzed, NO-mediated vasodilation as well as deficits in arterial contractile function. Reduced myogenic tone in allograft resistance arteries increases coronary blood flow such that hydrostatic pressure surpasses oncotic pressure, causing cardiac interstitial edema. This generalized edema decreases ventricular compliance leading to heart failure during the course of acute immune rejection of the graft. Cyclosporine A treatment reduces immune mediated dysregulation of myogenic tone, resulting in reduced interstitial edema and improved cardiac function. In this review, we discuss aspects of TVD and myogenic tone signaling mechanisms and how aberrations in myogenic regulation of arterial tone contribute to functional changes observed in cardiac transplant.
Moien-Afshari
Farzad
F
Department of Pharmacology and Therapeutics, Faculty of Medicine, University of British Columbia, Vancouver, Canada.
Skarsgard
Peter L
PL
McManus
Bruce M
BM
Laher
Ismail
I
D000818:Animals; D003331:Coronary Vessels / Q000502:physiology*; D016027:Heart Transplantation / Q000502:physiology*; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D018006:Myogenic Regulatory Factors / Q000502:physiology; D014655:Vascular Resistance / Q000502:physiology*
D018006:Myogenic Regulatory Factors