Laboratory of Medical Investigation, LIM-51, Department of Clinical Medicine, University of São Paulo Medical School, São Paulo, Brazil.
Int J Exp Pathol. 2013 Jun;94(3):178-87. doi: 10.1111/iep.12025. Epub 2013 Apr 18.
The experimental model of aortocaval fistula is a useful model of cardiac hypertrophy in response to volume overload. In the present study it has been used to investigate the pathologic subendocardial remodeling associated with the development of heart failure during the early phases (day 1, 3, and 7) following volume overload. Compared with sham treated rats, aortocaval fistula rats showed lower systemic blood pressure and higher left ventricular end-diastolic pressure This resulted in lower coronary driving pressure and left ventricular systolic and diastolic dysfunction. Signs of myocyte necrosis, leukocyte cell infiltration, fibroplasia and collagen deposition appeared sequentially in the subendocardium where remodeling was more prominent than in the non-subendocardium. Accordingly, increased levels of TNF-alpha, IL-1 beta, and IL-6, and enhanced MMP-2 activity were all found in the subendocardium of rats with coronary driving pressure ≤ 60 mmHg. The coronary driving pressure was inversely correlated with MMP-2 activity in subendocardium in all time-points studied, and blood flow in this region showed positive correlation with systolic and diastolic function at day 7. Thus the predominant subendocardial remodeling that occurs in response to low myocardial perfusion pressure during the acute phases of aortocaval fistula contributes to early left ventricular dysfunction.
腔静脉-主动脉瘘模型是一种研究心脏对容量超负荷反应性肥大的有用模型。本研究应用该模型在容量超负荷早期（术后第 1、3 和 7 天）观察心力衰竭相关的心肌内下壁重构。与假手术组比较，腔静脉-主动脉瘘组大鼠表现为较低的全身血压和较高的左室舒张末压，这导致较低的冠状动脉灌注压和左室收缩及舒张功能障碍。心肌细胞坏死、白细胞浸润、纤维形成和胶原沉积的征象在内膜下心肌顺序出现，且重构比心外膜下心肌更为显著。因此，在冠状动脉灌注压≤60mmHg 的大鼠心内膜下发现 TNF-α、IL-1β和 IL-6 水平增加，MMP-2 活性增强。在所有研究时间点，冠状动脉灌注压与心内膜下 MMP-2 活性呈负相关，并且在第 7 天，该区域的血流与收缩和舒张功能呈正相关。因此，在腔静脉-主动脉瘘的急性早期，由于心肌灌注压低导致的主要心内膜下重构导致左室早期功能障碍。
