Mechanical work and energetic analysis of eccentric cardiac remodeling in a volume overload heart failure in rats

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.