In Vivo Metabolic Imaging of Cardiac Bioenergetics in Transgenic Mice

Ömerovic, Elmir; Madhu, Basetti; Bollano, Entela; Bohlooly, Mohammed; Törnell, Jan; Isgaard, Jörgen; Hjalmarson, Å; Soussi, B.; Waagstein, Finn

doi:10.1006/bbrc.2000.2518

Cited by 33 publications

(31 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The values of metabolite contents determined by NMR spectroscopy of the perfused hearts showed a significant 10% decrease in PCr-to-ATP ratio in CH hearts ( Table 2, P Ͻ 0.01). These results may be related to the classical energetic failure observed in hypoxia (19,32,40). MoCA analysis.…”

Section: Resultsmentioning

confidence: 67%

Modular control analysis of effects of chronic hypoxia on mouse heart

Calmettes

Deschodt-Arsac²,

Thiaudière³

et al. 2008

American Journal of Physiology-Regulatory, Integrative and Comp

View full text Add to dashboard Cite

R13-R19, 2007) was applied here on perfused hearts to describe the modifications of the regulation of heart energetics induced in mice exposed to 3-wk chronic hypoxia. MoCA combines 31 P-NMR spectroscopy and modular (top down) control analysis to describe the integrative regulation of energy metabolism in the intact beating heart, on the basis of two modules [ATP/phosphocreatine (PCr) production and ATP/PCr consumption] connected by the energetic intermediates. In contrast with previous results in rat heart, in which all control of contraction was on ATP demand, mouse heart energetics presented a shared control of contraction between ATP/PCr-producing and -consuming modules. In chronic hypoxic mice, the decrease in heart contractile activity and PCr-to-ATP ratio was surprisingly associated with an important and significant higher response of ATP/PCr production (elasticity) to PCr changes compared with control hearts (Ϫ10.4 vs. Ϫ2.46). By contrast, no changes were observed in ATP/PCr consumption since comparable elasticities were observed. Since elasticities determine the regulation of energetics of heart contraction, the present results show that this new parameter may be used to uncover the origin of the observed dysfunctions under chronic hypoxia conditions. Considering the decrease in mitochondrial content reported after exposure to chronic hypoxia, it appears that the improvement of ATP/PCr production response to ATP demand may be viewed as a positive adaptative mechanism. It now appears crucial to understand the very processes responsible for ATP/PCr producer elasticity toward the energetic intermediates, as well as their regulation. perfused mouse heart; systems biology; 31 P-labeled magnetic resonance spectroscopy CHRONIC HYPOXIA (CH) induces numerous adaptative changes in heart physiology, including remodeling. Indeed, in addition to the effect of lowered oxygen availability on oxidative cardiac metabolism, the heart is submitted to an increased workload as a result of the hypoxia-induced pulmonary hypertension (21,22). This pathological situation induces complex structural, hormonal, and biochemical modifications that affect both energy-producing and energy-consuming processes in heart cells (see Refs. 20,33). Concerning energy-producing modifications, an important reduction in the mitochondrial mass has been observed, associated with the reduction of the activities of respiratory chain complexes (29). In parallel, several studies reported a metabolic switch from fatty acid to carbohydrate utilization after CH (13,25,28,36,37). In regard to energyconsuming processes, one of the early mechanisms observed in isolated mammalian cardiomyocytes submitted to acute hypoxia is a downregulation of protein and RNA synthesis (9, 34). Moreover, biochemical investigations under CH also revealed a modification of the contractile apparatus itself, characterized by an increase in ␤-myosin heavy chain expression in both ventricles (35). These modifications of ATP/phosphocreatine (PCr) production and consumption proces...

show abstract

Section: Resultsmentioning

confidence: 67%

Modular control analysis of effects of chronic hypoxia on mouse heart

Calmettes

Deschodt-Arsac²,

Thiaudière³

et al. 2008

American Journal of Physiology-Regulatory, Integrative and Comp

View full text Add to dashboard Cite

show abstract

“…The effects of general overexpression of GH are known from the studies performed on transgenic mice with overexpression of bovine GH in the whole body [10,[26][27][28][29]. These animals are characterised by increased total BW as well as increased weight of other internal organs including the heart.…”

Section: Discussionmentioning

confidence: 99%

“…The MR imaging and spectroscopy experiments were performed on a 2.35 Tesla (T) horizontal magnet with a 20-cm bore (Bruker Biospec 24/30) interfaced with an X-32 acquisition system giving operating frequencies for 1 H and 31 P MR 100 and 40.5 MHz, respectively. The experiments were performed according to the procedure as previously described [10]. The size of the volume of interest (VOI) for cardiac spectroscopy was 8 · 4 · 4 mm 3 (128 lL, Figs.…”

Section: In Vivo Volume-selective 31 P Mrs Of Heart and Brainmentioning

confidence: 99%

Selective cerebral overexpression of growth hormone alters cardiac function, morphology, energy metabolism and catcholamines in transgenic mice

Bohlooly‐Y

Bollano

Mobini

et al. 2005

Growth Hormone & IGF Research

Self Cite

View full text Add to dashboard Cite

“…Left thoracotomy was performed and 500 000 hES diluted in 50 μL hES were injected with a 31 gauge needle directly into the anterior part of the LV wall at a single injections site. The MR imaging experiments were performed on a 2.35 Tesla (T) horizontal magnet with a 20 cm bore Bruker Biospec 24/30 magnet according to the procedure previously described (Omerovic et al, 2000(Omerovic et al, , 1999. In vivo MRI of the heart was performed 24 h and 5 days after the transplantation of the hES under 1% isoflurane anesthesia.…”

Section: In Vivo Mrimentioning

confidence: 99%