The healing process is a key determinant for postinfarction left ventricular (LV) remodeling and the development of
heart failure, which could be influenced by mechanical (pressure and/or volume) load. So far, limited information exists regarding an indepth characterization of the postinfarct healing process in the mechanically unloaded state. In the present work, we performed isogenic Lewis-to-Lewis rat abdominal heterotopic
heart transplantation, which is characterized by hemodynamic unloading in the left ventricle, and simultaneously ligated the left anterior descending coronary artery (T-
infarct group). Pathological evolution was dynamically compared with that of in situ infarcted Lewis hearts (I-
infarct group) on days 3, 7, 14, and 35. There was a remarkable myocardial salvage in the unloaded heart, as shown by the improvement in
infarct size (T-
infarct group: 25.47% ± 4.31%
vs. I-
infarct group: 38.46% ± 4.82%, P < 0.01) and the smaller fraction of
fibrosis in
infarct segments (T-
infarct group: 42.12% ± 8.40%
vs. I-
infarct group: 75.65% ± 10.51%, P < 0.01). In addition, there was a progressive disorganization of the two-dimensional
collagen fiber alignment as well as retarded
collagen fiber maturation in the T-
infarct group. We also observed enhanced angiogenesis, lymphangiogenesis, and inflammatory cell retention in the
infarct region during mechanical unloading. Moreover, capillary density and
collagen deposition were significantly increased in the noninfarcted area of the unloaded heart compared with the same region in the in situ infarcted heart. In conclusion, ischemic insult in the mechanically unloaded heart elicits an altered inflammatory and healing response, which is characterized by myocardial salvage, delayed resolution of
inflammation, and disorganization of the
collagen orientation in the infarcted region. These findings could provide novel insights into the contribution of hemodynamic load in the postinfarction healing process. Further studies are warranted to elucidate its potential mechanism.