AJP - Heart Calcium Transients and Cell-Sarcomere
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Am J Physiol Heart Circ Physiol 293: H1046-H1052, 2007. First published May 4, 2007; doi:10.1152/ajpheart.01040.2006
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Continuous inhalation of carbon monoxide induces right ventricle ischemia and dysfunction in rats with hypoxic pulmonary hypertension

Mathieu Gautier,1 Daniel Antier,1 Pierre Bonnet,1 Jean-Loic Le Net,2 Gilles Hanton,2 and Veronique Eder1

1University Francois Rabelais of Tours, IFR 135, Labpart EA 3852, Tours Cedex; and 2Pfizer Global Research and Development, Centre de Recherche, Amboise Cedex, France

Submitted 22 September 2006 ; accepted in final form 3 May 2007

We aimed to investigate the toxicity of carbon monoxide (CO) in rats with right ventricle (RV) remodeling induced by hypoxic pulmonary hypertension (PHT). A group of Wistar rats was exposed to 3-wk hypobaric hypoxia (H). A second group was exposed to 50 ppm CO for 1 wk (CO). A third group was exposed to chronic hypoxia including 50 ppm CO during the third week (H+CO). These groups were compared with controls. RV and left ventricle (LV) functions were assessed by echocardiography and transparietal catheterization. Ventricular perfusion was estimated with the fluorescent microsphere method. Results were confirmed by histology. PHT induced RV hypertrophy and function enhancement. In the H group, RV shortening fraction (RVSF; 71 ± 12% vs. 41 ± 2%) and RV end-systolic pressure (RVESP; 54 ± 6 vs. 19 ± 2 mmHg) were increased compared with controls. Moreover, myocardial perfusion was increased in the RV (36 ± 2% vs. 22 ± 2%) and decreased in the LV (64 ± 3% vs. 78 ± 2%). In the H+CO group, RVSF (45 ± 3% vs. 71 ± 12%) and RVESP (38 ± 3 vs. 54 ± 6 mmHg) were decreased compared with the H group. RV perfusion was decreased in the H+CO group compared with the H group (21 ± 5% vs. 36 ± 2%), and LV perfusion was increased (79 ± 5% vs. 64 ± 3%). PHT and RV hypertrophy were still present in the H+CO group, and fibroses localized in the RV were detected. Similar lesions were observed in an additional group exposed simultaneously to hypoxia and 50 ppm CO over 3 wk. We demonstrated that rats with established PHT were more sensitive to CO, which dramatically alters the RV adaptive response to PHT, leading to ischemic lesions.

right ventricle remodeling; right ventricle perfusion



Address for reprint requests and other correspondence: V. Eder, Labpart EA 3852, Fac. of Medicine, Univ. Francois Rabelais, 10 Bld Tonnelle, BP 3223, 37032 Tours Cedex 1, France (e-mail: eder{at}med.univ-tours.fr)







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