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This Article Full Text Full Text (PDF) All Versions of this Article: 296/4/H1117    most recent 01120.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Takewa, Y. Articles by Hajjar, R. J. Search for Related Content PubMed PubMed Citation Articles by Takewa, Y. Articles by Hajjar, R. J.

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

¹Cardiovascular Research Center, Mount Sinai School of Medicine, New York, New York; ²Department of Physiology II, Nara Medical University School of Medicine, Nara; and ³Department of Artificial Organs, National Cardiovascular Center Research Institute, Osaka, Japan; and ⁴Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts

Submitted 24 October 2008 ; accepted in final form 3 February 2009

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 O₂ 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 O₂ consumption related to Ca²⁺ handling significantly decreased. The contractile response to Ca²⁺ infusion was attenuated. Nevertheless, the increase in Ca²⁺ handling-related O₂ 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 Ca²⁺-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 Ca²⁺ handling processes. These results suggest that restoring Ca²⁺ handling in excitation-contraction coupling would improve the contractility of the myocardium after eccentric cardiac remodeling.

eccentric left ventricular hypertrophy; myocardial oxygen consumption; Ca²⁺ handling; sarco(endo)plasmic reticulum Ca²⁺-ATPase 2a; cross circulation; aortocaval shunt

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