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This Article Full Text Full Text (PDF) All Versions of this Article: 295/6/R1891    most recent 90548.2008v1 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 Web of Science (2) Citing Articles via Google Scholar Google Scholar Articles by Calmettes, G. Articles by Diolez, P. Search for Related Content PubMed PubMed Citation Articles by Calmettes, G. Articles by Diolez, P.

NEUROHUMORAL CONTROL OF CARDIOVASCULAR FUNCTION

Modular control analysis of effects of chronic hypoxia on mouse heart

¹Résonance Magnétique des Systèmes Biologiques, UMR5536, Centre National de la Recherche Scientifique and ²Laboratoire de Pharmacologie de l'UFR Pharmacie, Institut National de la Santé et de la Recherche Médicale U885, Université Victor Segalen Bordeaux 2, Bordeaux, France

Submitted 30 June 2008 ; accepted in final form 26 September 2008

Modular control analysis (MoCA; Diolez P, Deschodt-Arsac V, Raffard G, Simon C, Santos PD, Thiaudiere E, Arsac L, Franconi JM. Am J Physiol Regul Integr Comp Physiol 293: 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 ³¹P-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 (–10.4 vs. –2.46). 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; ³¹P-labeled magnetic resonance spectroscopy