Takewa Yoshiaki, Chemaly Elie R, Takaki Miyako, Liang Li Fan, Jin Hongwei, Karakikes Ioannis, Morel Charlotte, Taenaka Yoshiyuki, Tatsumi Eisuke, Hajjar Roger J
Cardiovascular Research Center, Mount Sinai School of Medicine, One Gustave Levy Place, Box 1030, New York, NY 10029, USA.
Am J Physiol Heart Circ Physiol. 2009 Apr;296(4):H1117-24. doi: 10.1152/ajpheart.01120.2008. Epub 2009 Feb 6.
Eccentric cardiac remodeling seen in dilated cardiomyopathy or regurgitant valvular disease is a well-known process of heart failure progression, but its mechanoenergetic profile has not been yet established. We made a volume overload (VO) heart failure model in rats and for the first time investigated left ventricular (LV) mechanical work and energetics in cross-circulated whole heart preparations. Laparotomy was performed in 14 Wistar male rats, and abdominal aortic-inferior vena caval shunt was created in seven rats (VO group). Another seven rats underwent a sham operation without functional shunt (Sham group). LV dimensions changes were followed with weekly transthoracic echocardiography. Three months after surgery, we measured LV pressure and volume and myocardial O(2) consumption in isolated heart cross circulation. LV internal dimensions in both systolic and diastolic phases were significantly increased in the VO group versus the Sham group (P < 0.05). LV pressure was markedly decreased in the VO group versus in the Sham group (P < 0.05). LV end-systolic pressure-volume relation shifted downward, and myocardial O(2) consumption related to Ca(2+) handling significantly decreased. The contractile response to Ca(2+) infusion was attenuated. Nevertheless, the increase in Ca(2+) handling-related O(2) consumption per unit change in LV contractility in the VO group was significantly higher than that in the Sham group (P < 0.05). The levels of sarco(endo)plasmic reticulum Ca(2+)-ATPase 2a protein were reduced in the VO group (P < 0.01). In conclusion, VO failing rat hearts had a character of marked contractile dysfunction accompanied with less efficient energy utilization in the Ca(2+) handling processes. These results suggest that restoring Ca(2+) handling in excitation-contraction coupling would improve the contractility of the myocardium after eccentric cardiac remodeling.
扩张型心肌病或瓣膜反流性疾病中出现的离心性心脏重塑是心力衰竭进展的一个众所周知的过程，但其机械能量学特征尚未确定。我们在大鼠中建立了容量超负荷（VO）心力衰竭模型，并首次在交叉循环的全心制备中研究了左心室（LV）的机械功和能量学。对14只雄性Wistar大鼠进行剖腹手术，7只大鼠建立腹主动脉-下腔静脉分流术（VO组）。另外7只大鼠接受假手术，不进行功能性分流（假手术组）。每周通过经胸超声心动图监测左心室尺寸变化。术后三个月，我们在离体心脏交叉循环中测量左心室压力和容积以及心肌氧耗。与假手术组相比，VO组收缩期和舒张期的左心室内径均显著增加（P<0.05）。与假手术组相比，VO组的左心室压力显著降低（P<0.05）。左心室收缩末期压力-容积关系向下移位，与钙处理相关的心肌氧耗显著降低。对钙输注的收缩反应减弱。然而，VO组每单位左心室收缩性变化中与钙处理相关的氧耗增加显著高于假手术组（P<0.05）。VO组肌浆网钙-ATP酶2a蛋白水平降低（P<0.01）。总之，VO衰竭大鼠心脏具有明显的收缩功能障碍特征，同时在钙处理过程中的能量利用效率较低。这些结果表明，恢复兴奋-收缩偶联中的钙处理将改善离心性心脏重塑后心肌的收缩性。
