title: Characterization of right ventricular function after monocrotaline-induced pulmonary hypertension in the intact rat.
abstract: We characterized hemodynamics and systolic and diastolic right ventricular (RV) function in relation to structural changes in the rat model of monocrotaline (MCT)-induced pulmonary hypertension. Rats were treated with MCT at 30 mg/kg body wt (MCT30, n = 15) and 80 mg/kg body wt (MCT80, n = 16) to induce compensated RV hypertrophy and RV failure, respectively. Saline-treated rats served as control (Cont, n = 13). After 4 wk, a pressure-conductance catheter was introduced into the RV to assess pressure-volume relations. Subsequently, rats were killed, hearts and lungs were rapidly dissected, and RV, left ventricle (LV), and interventricular septum (IVS) were weighed and analyzed histochemically. RV-to-(LV + IVS) weight ratio was 0.29 +/- 0.05 in Cont, 0.35 +/- 0.05 in MCT30, and 0.49 +/- 0.10 in MCT80 (P < 0.001 vs. Cont and MCT30) rats, confirming MCT-induced RV hypertrophy. RV ejection fraction was 49 +/- 6% in Cont, 40 +/- 12% in MCT30 (P < 0.05 vs. Cont), and 26 +/- 6% in MCT80 (P < 0.05 vs. Cont and MCT30) rats. In MCT30 rats, cardiac output was maintained, but RV volumes and filling pressures were significantly increased compared with Cont (all P < 0.05), indicating RV remodeling. In MCT80 rats, RV systolic pressure, volumes, and peak wall stress were further increased, and cardiac output was significantly decreased (all P < 0.05). However, RV end-systolic and end-diastolic stiffness were unchanged, consistent with the absence of interstitial fibrosis. MCT-induced pressure overload was associated with a dose-dependent development of RV hypertrophy. The most pronounced response to MCT was an overload-dependent increase of RV end-systolic and end-diastolic volumes, even under nonfailing conditions.
authors.affiliation: Dept. of Cardiology, C5-P, Leiden Univ. Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands.
authors.forename: Marleen H M
authors.initials: MH
authors.lastname: Hessel
authors.forename: Paul
authors.initials: P
authors.lastname: Steendijk
authors.forename: Brigit
authors.initials: B
authors.lastname: den Adel
authors.forename: Cindy I
authors.initials: CI
authors.lastname: Schutte
authors.forename: Arnoud
authors.initials: A
authors.lastname: van der Laarse
mesh_terms: D000818:Animals; D001794:Blood Pressure; D002302:Cardiac Output; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D017380:Hypertrophy, Right Ventricular / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D007150:Immunohistochemistry; D008297:Male; D016686:Monocrotaline; D009929:Organ Size; D051381:Rats; D017208:Rats, Wistar; D013318:Stroke Volume; D013997:Time Factors; D018497:Ventricular Dysfunction, Right / Q000139:chemically induced / Q000503:physiopathology*; D017725:Ventricular Pressure
chemical_list: D016686:Monocrotaline