Selected Contribution: Pulmonary hypertension in mice following intermittent hypoxia.
Sleep apnea (intermittent periods of hypoxia with or without hypercapnia) is associated with systemic hypertension and increased mortality from cardiovascular disease, but the relationship to pulmonary hypertension is uncertain. Previous studies on intermittent hypoxia (IH) in rats that demonstrated pulmonary hypertension utilized relatively long periods of hypoxia. Recent studies that utilized brief periods of hypoxia have conflicting reports of right ventricular (RV) hypertrophy. In addition, many studies have not measured pulmonary hemodynamics to asses the severity of pulmonary hypertension in vivo. Given the increasing availability of genetically engineered mice and the need to establish a rodent model of IH-induced pulmonary hypertension, we studied the effect of IH (2-min cycles of 10% and 21% O2, 8 h/day, 4 wk) on wild-type mice, correlating in vivo measurements of pulmonary hypertension with RV mass and pulmonary vascular remodeling. RV systolic pressure was increased after IH (36 +/- 0.9 mmHg) compared with normoxia (29.5 +/- 0.6) but was lower than continuous hypoxia (44.2 +/- 3.4). RV mass [RV-to-(left ventricle plus septum) ratio] correlated with pressure measurements (IH = 0.27 +/- 0.02, normoxia = 0.22 +/- 0.01, and continuous hypoxia = 0.34 +/- 0.01). Hematocrits were also elevated after IH and continuous hypoxia (56 +/- 1.6 and 54 +/- 1.1 vs. 44.3 +/- 0.5%). Evidence of neomuscularization of the distal pulmonary circulation was found after IH and continuous hypoxia. We conclude that mice develop pulmonary hypertension following IH, representing a possible animal model of pulmonary hypertension in response to the repetitive hypoxia-reoxygenation of sleep apnea.
Fagan
K A
KA
Cardiovascular Pulmonary Research Laboratory, Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA. karen.fagan@uchsc.edu
D000818:Animals; D006400:Hematocrit; D006439:Hemodynamics / Q000502:physiology; D006976:Hypertension, Pulmonary / Q000209:etiology* / Q000503:physiopathology; D017380:Hypertrophy, Right Ventricular / Q000473:pathology; D000860:Hypoxia / Q000150:complications*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic / Q000473:pathology; D010101:Oxygen Consumption / Q000502:physiology; D011086:Polycythemia / Q000209:etiology / Q000503:physiopathology