Submitted on September 22, 2006
Accepted on May 3, 2007
Continuous inhalation of carbon monoxide induces right ventricle ischemia and dysfunction in rat with hypoxic pulmonary hypertension
Mathieu Gautier1, Daniel Antier1, Pierre Bonnet2, Jean-Loic LeNet3, Gilles Hanton3, and Eder Veronique4*
1 LABPART, FACULTY, CHAMBRAY LES TOURS, France; Labpart, Universite tours, Tours, France
2 Faculté de Médecine, LABPART, Tours, France; LABPART, FACULTY, CHAMBRAY LES TOURS, France; Labpart, Universite tours, Tours, France
3 Centre de Recherche, Pfizer Global Research & Development, Amboise, France
4 LABPART, FACULTY, CHAMBRAY LES TOURS, France
* To whom correspondence should be addressed. E-mail: eder{at}med.univ-tours.fr.
We aimed to investigate the toxicity of carbon monoxide (CO) in rats with right ventricle (RV) remodeling induced by hypoxic pulmonary hypertension (PHT). Wistar rats were exposed to 3 weeks hypobaric hypoxia (H). A second group was exposed to 50 ppm CO for one week (CO). A third group was exposed to chronic hypoxia including 50 ppm CO during the third week (HCO). These groups were compared to controls. RV and left ventricle (LV) functions were assessed by Echocardiography and transparietal catheterism. Ventricular perfusion was estimated using the fluorescent microspheres 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 %) as well as RV end-systolic pressure (RVESP) (54±6 mmHg vs 19±2 mmHg) were increased compared to controls. Moreover, myocardial perfusion was increased in RV (36±2 % vs 22±2 %) and decreased in LV (64±3 % vs 78±2 %). In the HCO group, RVSF (45±3 % vs 71±12 %) and RVESP (38±3 mmHg vs 54±6 mmHg) were decreased compared to the H group. RV perfusion was decreased in HCO group compared to the H group (21±5 % vs 36±2 %) and LV perfusion was increased (79±5 % vs 64±3 %). PHT as well as RV hypertrophy were still present in HCO group and fibroses localized in RV were detected. Similar lesions were observed in additional group exposed simultaneously to hypoxia and 50 ppm CO during three weeks. 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.
