Continuous inhalation of carbon monoxide induces right ventricle ischemia and dysfunction in rats with hypoxic pulmonary hypertension.
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.
Gautier
Mathieu
M
University Francois Rabelais of Tours, IFR 135, Labpart EA 3852, Tours Cedex, France.
Antier
Daniel
D
Bonnet
Pierre
P
Le Net
Jean-Loic
JL
Hanton
Gilles
G
Eder
Veronique
V
D000280:Administration, Inhalation; D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002248:Carbon Monoxide / Q000008:administration & dosage / Q000633:toxicity*; D002263:Carboxyhemoglobin / Q000378:metabolism; D006328:Cardiac Catheterization; D003326:Coronary Circulation / Q000187:drug effects; D004195:Disease Models, Animal; D004452:Echocardiography; D005355:Fibrosis; D006352:Heart Ventricles / Q000187:drug effects / Q000503:physiopathology; D006400:Hematocrit; D006976:Hypertension, Pulmonary / Q000097:blood / Q000150:complications* / Q000209:etiology / Q000503:physiopathology; D017380:Hypertrophy, Right Ventricular / Q000097:blood / Q000209:etiology* / Q000503:physiopathology; D000860:Hypoxia / Q000097:blood / Q000150:complications* / Q000503:physiopathology; D017078:Laser-Doppler Flowmetry; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D017202:Myocardial Ischemia / Q000139:chemically induced* / Q000150:complications / Q000473:pathology / Q000503:physiopathology; D011651:Pulmonary Artery / Q000187:drug effects / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D016277:Ventricular Function, Left / Q000187:drug effects; D016278:Ventricular Function, Right / Q000187:drug effects*; D017725:Ventricular Pressure / Q000187:drug effects; D020257:Ventricular Remodeling / Q000187:drug effects*
D002248:Carbon Monoxide; D002263:Carboxyhemoglobin