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Induction of left ventricular remodeling and dysfunction in the recipient heart after donor heart myocardial infarction

new insights into the pathologic role of tumor necrosis factor-alpha from a novel heterotopic transplant–coronary ligation rat model

Hiroshi Nakamura, MD, PhD^*,*, Seiji Umemoto, MD, PhD^*, George Naik, BSc, Gordon Moe, MD, FACC, Satoko Takata, MD^*, Peter Liu, MD, FACC and Masunori Matsuzaki, MD, PhD, FACC^*

^* Department of Cardiovascular Medicine, Yamaguchi University School of Medicine, Ube, Japan
St. Michael’s Hospital, Toronto, Canada
Centre for Cardiovascular Research, The Toronto Hospital, and University of Toronto, Toronto, Canada

View larger version (53K): [in a new window]   Figure 1 An anatomic scheme of cardiac transplantation and simultaneous coronary artery ligation. Isogenic heterotopic cardiac transplantation was performed by end-to-side anastomosis of the ascending aorta of the donor heart to the abdominal aorta of the recipient and donor pulmonary artery to the recipient inferior vena cava. Note that coronary ligation was performed only in the donor heart.

View larger version (19K): [in a new window]   Figure 2 Time course of plasma tumor necrosis factor (TNF)-alpha and angiotensin II (ANG II) concentrations after surgery. Plasma ANG II concentrations showed no difference between the two groups at any time point (lower panel), whereas plasma TNF-alpha concentrations were significantly increased at 2, 4, and 7 days after surgery, compared with the sham group (upper panel). Data are expressed as the mean ± SD (n = 6). *p < 0.05 vs. sham group.

View larger version (20K): [in a new window]   Figure 3 Tissue tumor necrosis factor-alpha (TNF)-alpha concentrations and angiotensin II (ANG II) content of the donor and recipient hearts on day 7. The tissue ANG II content was significantly increased only at the infarct region, whereas tissue TNF-alpha concentrations were significantly increased only in the recipient heart of the ligation group. Data are expressed as the mean ± SD (n = 6). *p < 0.05 vs. all of the other regions.

View larger version (17K): [in a new window]   Figure 4 Semiquantitative polymerase chain reaction analysis of tumor necrosis factor (TNF)-alpha messenger ribonucleic acid (mRNA) in the recipient heart. Total tissue ribonucleic acid was separated and analyzed on day 7. Data are expressed as the mean ± SD (n = 4). *p < 0.05 vs. sham group.

View larger version (109K): [in a new window]   Figure 5 Photomicrographs of immunostained tumor necrosis factor (TNF)-alpha–positive cells in cross sections of the recipient heart in the ligation group (a, b) and the sham group (c). (a, b) Many monocytes expressing TNF-alpha were observed only in the vessels. Arrows indicate TNF-alpha-positive cells. (c) TNF-alpha-expressing cells were not observed in the recipient heart of the sham group. Scale bar = 50 µm.