AJP - Heart Calcium Transients and Cell-Sarcomere
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Am J Physiol Heart Circ Physiol (February 6, 2009). doi:10.1152/ajpheart.01120.2008
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Submitted on October 24, 2008
Revised on January 21, 2009
Accepted on February 3, 2009

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

Yoshiaki Takewa1, Elie R Chemaly1, Miyako Takaki2, Li Fan Liang1, Hongwei Jin1, Ioannis Karakikes1, Charlotte Morel1, Yoshiyuki Taenaka3, Eisuke Tatsumi3, and Roger J Hajjar1*

1 Mount Sinai School of Medicine
2 Nara Medical University
3 National Cardiovascular Center Research Institute

* To whom correspondence should be addressed. E-mail: roger.hajjar{at}mssm.edu.

Eccentric cardiac remodeling in dilated cardiomyopathy or regurgitant valvular disease is a well-known process of heart failure progression, but its mechanoenergetic profile has not yet been established. We made a volume-overload 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 7 rats (VO group). Another 7 rats underwent a sham operation without functional shunt (Sham group). LV dimension changes were followed with weekly transthoracic echocardiography. Three months after surgery, we measured LV pressure and volume, and myocardial oxygen consumption in isolated heart cross-circulation. LV internal dimensions in both systolic and diastolic phases (LVIDs and LVIDd) were significantly increased in VO group versus Sham group (P<0.05). LV pressure was markedly decreased in VO group than that in Sham group (P<0.05). LV end-systolic pressure-volume relation shifted downward and myocardial oxygen consumption related to Ca2+ handling significantly decreased. The contractile response to Ca2+ infusion was attenuated. Nevertheless, the increase in oxygen consumption related to Ca2+ handling and excitation-contraction coupling per unit change in LV contractility in VO group was significantly higher than that in Sham group (P<0.05). The levels of SERCA2a protein were reduced in the VO group (p<0.01). In conclusion, volume-overloaded failing rat hearts were characterized by marked contractile dysfunction accompanied by a less efficient energy utilization in Ca2+ handling processes. Present results suggest the possibility that repairing Ca2+ handling in excitation-contraction coupling would improve the contractility of the myocardium after eccentric cardiac remodeling.




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Am. J. Physiol. Heart Circ. Physiol.Home page
C. Nakajima-Takenaka, G.-X. Zhang, K. Obata, K. Tohne, H. Matsuyoshi, Y. Nagai, A. Nishiyama, and M. Takaki
Left ventricular function of isoproterenol-induced hypertrophied rat hearts perfused with blood: mechanical work and energetics
Am J Physiol Heart Circ Physiol, November 1, 2009; 297(5): H1736 - H1743.
[Abstract] [Full Text] [PDF]




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