Cardiac dysfunction in terms of left ventricular mechanical work and energetics in hypothyroid rats

Ohga, Yoshimi; Satoh, Susumu; Takenaka, Chikako; Abe, Takeji; Tsuji, Tsuyoshi; Taniguchi, Shigeki; Takaki, Miyako

doi:10.1152/ajpheart.00046.2002

Cited by 40 publications

(69 citation statements)

References 40 publications

(93 reference statements)

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“…The slope of the V O 2 -PVA relation remained unchanged in hypothyroid (11) and diabetic (1) rat hearts, whereas a steeper slope of the V O 2 -PVA relation was reported in hyperthyroid rabbit hearts. It was reported that the slope of the V O 2 -PVA relation was related to the ratio of the myosin isoform component from predominantly V3 to predominantly V1 (i.e., the slope of the V O 2 -PVA relation increases when the V1-to-V3 ratio increases, and the slope of the V O 2 -PVA relation is unchanged when the V1-to-V3 ratio decreases) (6).…”

Section: Chemomechanical Energy Transductionmentioning

confidence: 83%

“…its V O2 intercept represents the PVA-independent V O2. The PVAindependent V O2 is composed of V O2 in excitation-contraction (E-C) coupling (18) and basal metabolism (11,17). The RV was kept collapsed (and therefore unloaded) by continuous hydrostatic drainage of the coronary venous return so that the RV PVA and hence PVA-dependent V O2 were assumed to be negligible (19,20).…”

Section: Mechanical and Energetic Studiesmentioning

confidence: 99%

“…Such parallelism was also observed in VO rat hearts in our preliminary experiments. The V O2-intercept (PVA-independent V O2) corresponds primarily to the V O2 for Ca 2ϩ handling in E-C coupling and for basal metabolism (11,17,18). The increased V O2 intercept of the Ca 2ϩ V O2-PVA relation is attributable to the increased V O2 for enhanced Ca 2ϩ handling due to the unchanged V O2 for basal metabolism (17).…”

Section: Data Analysis V O2 For Ca 2ϩ Handling During the Ca 2ϩ Ino-runmentioning

confidence: 99%

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

Takewa

Chemaly²,

Takaki³

et al. 2009

American Journal of Physiology-Heart and Circulatory Physiology

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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 Ͻ 0.05). LV pressure was markedly decreased in the VO group versus in the Sham group (P Ͻ 0.05). LV end-systolic pressurevolume relation shifted downward, and myocardial O2 consumption related to Ca 2ϩ handling significantly decreased. The contractile response to Ca 2ϩ infusion was attenuated. Nevertheless, the increase in Ca 2ϩ handling-related O2 consumption per unit change in LV contractility in the VO group was significantly higher than that in the Sham group (P Ͻ 0.05). The levels of sarco(endo)plasmic reticulum Ca 2ϩ -ATPase 2a protein were reduced in the VO group (P Ͻ 0.01). In conclusion, VO failing rat hearts had a character of marked contractile dysfunction accompanied with less efficient energy utilization in the Ca 2ϩ handling processes. These results suggest that restoring Ca 2ϩ handling in excitation-contraction coupling would improve the contractility of the myocardium after eccentric cardiac remodeling. eccentric left ventricular hypertrophy; myocardial oxygen consumption; Ca 2ϩ handling; sarco(endo)plasmic reticulum Ca 2ϩ -ATPase 2a; cross circulation; aortocaval shunt HEART FAILURE IS A MAJOR CAUSE of mortality and morbidity. It is due to various diseases such as hypertension, ischemic heart disease, valvular heart disease, congenital heart disease, cardiomyopathy, myocarditis, and others. The heart is subject to excessive and/or long-term overload, which induces myocardial hypertrophy. Hypertrophy initially compensates cardiac function but finally leads to heart failure. The process of hypertrophy and heart failure progression is divided into two mechanisms, depending on the type of overload: pressure overloading (PO) and volume overloading (VO). PO induces concentric hypertrophy to normalize wall stress from the increase in pressure placed on cardiomyocytes. Concentric remodeling of the left ventricle (LV) is characterized by an increase in ventricular wall thickness due to vertical growing of cardiomyocytes, which is caused by the parallel addition of sarcomeres (8).Conversely, VO promotes eccentric hypertrophy to compensate for excess blood volum...

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Section: Chemomechanical Energy Transductionmentioning

confidence: 83%

Section: Mechanical and Energetic Studiesmentioning

confidence: 99%

Section: Data Analysis V O2 For Ca 2ϩ Handling During the Ca 2ϩ Ino-runmentioning

confidence: 99%

See 1 more Smart Citation

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

Takewa

Chemaly²,

Takaki³

et al. 2009

American Journal of Physiology-Heart and Circulatory Physiology

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“…Interestingly, in the failing heart of hypothyroid rats, the O 2 consumption for total Ca 2? handling in the E-C coupling significantly decreased, but did not increase [40]. Thus, the remodeling of Ca 2?…”

Section: Discussionmentioning

confidence: 83%

“…PVA, which is a total mechanical energy per beat, has been shown to linearly relate with myocardial O 2 consumption per beat in in vitro cross-circulated (blood-perfused) rat hearts [23,40,47]. PVA-independent myocardial O 2 consumption at PVA = 0 corresponds to energy requirements for Ca 2? handling in E-C coupling and basal metabolism [15,23,32].…”

Section: Discussionmentioning

confidence: 99%

Increased O2 consumption in excitation–contraction coupling in hypertrophied rat heart slices related to increased Na+–Ca2+ exchange activity

et al. 2008

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The goal of our study was to evaluate the origin of the increased O 2 consumption in electrically stimulated left ventricular slices of isoproterenol-induced hypertrophied rat hearts with normal left ventricular pressure. O 2 consumption per minute (mVO 2 ) of mechanically unloaded left ventricular slices was measured in the absence and presence of 1-Hz field stimulation. Basal metabolic mVO 2 , i.e., mVO 2 without electrical stimulation, was significantly smaller, but mVO 2 for the total Ca 2? handling in excitation-contraction coupling (E-C coupling mVO 2 ), i.e., delta mVO 2 (=mVO 2 with stimulation -mVO 2 without stimulation), was significantly larger in the hypertrophied heart. Furthermore, the fraction of E-C coupling mVO 2 was markedly altered in the hypertrophied heart. Namely, mVO 2 consumed by sarcoplasmic reticulum Ca 2? -ATPase (SERCA2) was depressed by 40%; mVO 2 consumed by the Na ? /K ? -ATPase (NKA)-Na ? /Ca 2? exchange (NCX) coupling was increased by 100%. The depressed mVO 2 consumption by SERCA2 was supported by lower protein expressions of phosphorylated-Ser 16 phospholamban and SERCA2. The increase in NKA-NCX coupling mVO 2 was supported by marked augmentation of NCX current. However, the increase in NCX current was not due to the increase in NCX1 protein expression, but was attributable to attenuation of the intrinsic inactivation mechanisms. The present results demonstrated that the altered origin of the increased E-C coupling mVO 2 in hypertrophy was derived from decreased SERCA2 activity (1ATP: 2Ca 2? ) and increased NCX activity coupled to NKA activity (1ATP: Ca 2? ). Taken together, we conclude that the energetically less efficient Ca 2? extrusion pathway evenly contributes to Ca 2? handling in E-C coupling in the present hypertrophy model.

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Methods for the Preparation of an Excised, Cross-Circulated Rat Heart

Okihara

Takaki

2018

Methods in Molecular Biology

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The Emax-Pressure-Volume Area (PVA)-VO framework proposed by Dr. Suga for canine hearts has dramatically advanced the field of cardiac mechanical work and energetics, i.e., mechanoenergetics. He and his collaborators investigated mechanoenergetics in the left ventricle (LV) of excised, cross-circulated canine heart preparations. We instituted the excised cross-circulated rat whole heart preparations and found a curvilinear end-systolic pressure-volume relation (ESPVR) in the rat LV, in contrast to the linear ESPVR in canine, rabbit, and human LVs. Although Emax, the slope of the linear ESPVR, could be used as an index of LV contractility, it was not applicable for evaluating LV contractility in the rat LV. Thus, we proposed a new index of contractility, equivalent Emax (eEmax) in the rat LV. We also found a linear VO-PVA relationship in the rat LV. Here, we introduce the methods for the preparation of excised, cross-circulated rat whole hearts and the eEmax-PVA-VO framework in the rat LV. Using this method, we can obtain accurate LV volume and myocardial O consumption in real time for estimating cardiac mechanoenergetics, which is very challenging in in vivo experiments.

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Cardiac dysfunction in terms of left ventricular mechanical work and energetics in hypothyroid rats

Cited by 40 publications

References 40 publications

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

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

Increased O2 consumption in excitation–contraction coupling in hypertrophied rat heart slices related to increased Na+–Ca2+ exchange activity

Methods for the Preparation of an Excised, Cross-Circulated Rat Heart

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