Tobacco smoke exposure in either the donor or recipient before transplantation accelerates cardiac allograft rejection, vascular inflammation, and graft loss.
BACKGROUND
Tobacco exposure in cardiac transplant recipients, before and after transplantation, may increase the risk of cardiac allograft vasculopathy and allograft loss, but no direct evidence for this phenomenon is forthcoming. In this experimental study, we investigated early consequences of tobacco smoke exposure in cardiac transplant donors and recipients with an emphasis on alloinflammatory mediators of graft outcome.


RESULTS
Using heterotopic rat cardiac transplantation, we tested the effects of donor or recipient tobacco smoke exposure in 6 groups of animals (rat heterotopic cardiac transplantation) as follows: tobacco-naïve allogeneic rejecting controls (n=6), tobacco-naïve nonrejecting controls (n=3; killed on day 5 to simulate survival times of tobacco-treated animals), isografts (n=3), both donor and recipient rats exposed to tobacco smoke (n=4), only donor rats exposed to tobacco smoke (n=7), and only recipient rats exposed to tobacco smoke (n=6). Polymerase chain reaction studies of tissue and peripheral (systemic) protein expression were performed to evaluate inflammatory (tumor necrosis factor-alpha, interferon-gamma, interleukin-6) and alloimmune (interleukin-1 receptor 2, programmed cell death-1, and stromal cell-derived factor-1) pathways, as was histological analysis of the cardiac allografts. Our experiments reveal that pretransplantation tobacco exposure in donors and/or recipients results in heightened systemic inflammation and increased oxidative stress, reduces posttransplantation cardiac allograft survival by 33% to 57%, and increases intragraft inflammation (tumor necrosis factor-alpha, interferon-gamma, interleukin-6) and alloimmune activation (CD3, interleukin-1 receptor 2, programmed cell death-1, and stromal cell-derived factor-1) with consequent myocardial and vascular destruction.


CONCLUSIONS
These sentinel findings confirm that tobacco smoke exposure in either donors or recipients leads to accelerated allograft rejection, vascular inflammation, and graft loss. Molecular pathways that intersect as arbiters in this phenomenon include instigation of alloimmune activation associated with tobacco smoke-induced inflammation.
Division of Cardiology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Ashwani K
AK
Khanna
Jianping
J
Xu
Patricia A
PA
Uber
Allen P
AP
Burke
Claudia
C
Baquet
Mandeep R
MR
Mehra
D000818:Animals; D001808:Blood Vessels / Q000473:pathology*; D016207:Cytokines / Q000032:analysis / Q000276:immunology; D006084:Graft Rejection / Q000209:etiology*; D006085:Graft Survival; D016027:Heart Transplantation / Q000473:pathology*; D007249:Inflammation / Q000209:etiology*; D018384:Oxidative Stress; D051381:Rats; D014019:Tissue Donors; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*; D014184:Transplantation, Homologous
D016207:Cytokines; D014028:Tobacco Smoke Pollution