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J Appl Physiol (July 7, 2005). doi:10.1152/japplphysiol.00411.2005
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Submitted on April 12, 2005
Accepted on June 30, 2005

THE ACUTE AND CHRONIC CARDIOVASCULAR EFFECTS OF INTERMITTENT HYPOXIA IN C57BL/6J MICE

M. J. Campen1, L. A. Shimoda2, and C. P. O'Donnell3*

1 Division of Toxicology, Lovelace Respiratory Research Institute, Albuquerque, NM, USA
2 Department of of Medicine, Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
3 Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

* To whom correspondence should be addressed. E-mail: odonnellcp{at}upmc.edu.

We investigated the effects of (1) acute hypoxia and (2) five weeks of chronic intermittent hypoxia (IH) on the systemic and pulmonary circulations of C57BL/6J mice. Mice were chronically instrumented with either femoral artery or right ventricular catheters. In response to acute hypoxia (four minutes of 10% O2; n=6) systemic arterial blood pressure fell (P<0.005) from 107.7 ± 2.5 to 84.7 ± 6.5 mmHg while right ventricular pressure increased (P<0.005) from 11.7 ± 0.8 to 14.9 ± 1.3 mmHg. Another cohort of mice was then exposed to IH for 5 weeks (O2 nadir = 5%, 60 second cycles, 12 h/day), then implanted with catheters. In response to five weeks of chronic IH, mice (n=8) increased systemic blood pressure by 7.5 mmHg, left ventricle (LV)+septum weight by 32.2 ± 7.5 x10 mg/100g b.w. (P<0.015), and right ventricle (RV) weight by 19.3 ± 3.2 x10 mg/100g b.w. (P<0.001), resulting in a 14% increase in the RV/LV+septum weight (P<0.005). We conclude that in C57BL/6J mice, (1) acute hypoxia causes opposite effects on the pulmonary and systemic circulations leading to preferential loading of the right heart, and (2) chronic IH in mice results in mild to moderate systemic and pulmonary hypertension, with resultant left and right-sided ventricular hypertrophy.




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