Supplemental oxygen reduces right ventricular hypertrophy in monocrotaline-injected rats.
We evaluated the possible contributory role of hypoxia in the development of monocrotaline-induced pulmonary hypertension. Male Sprague-Dawley rats were injected subcutaneously with monocrotaline (60 mg/kg) or saline in controls and were kept in oxygen-enriched (inspired O2 fraction of 0.35) or compressed air chambers. After 21 days, rats were anesthetized while spontaneously breathing room air, hemodynamic parameters and arterial blood gases were measured, and animals were killed. Right ventricular peak systolic pressures (RVPP), right ventricular-to-left ventricular plus septal weight ratios (RV/LV + S), hematocrits, lung dry weight-to-body weight ratios, and medial thickness of pulmonary arteries were significantly reduced in monocrotaline-injected rats exposed to mild hyperoxia compared with air. The air-exposed monocrotaline-injected rats had significantly more arterial hypoxemia than the other groups, and mild hyperoxia had no effect on any of the measured variables in saline-injected rats. To determine whether the effects of mild hyperoxia occurred early or late after monocrotaline injection, we moved separate groups of rats from air to mild hyperoxia and vice versa 10 days after monocrotaline injection. After 21 days, significant reductions in RVPP and RV/LV + S occurred only in rats exposed to mild hyperoxia during the latter 11 days after injection. Our findings suggest that hypoxia contributes to the development of pulmonary hypertension relatively late after monocrotaline injection in rats but that it does not influence the early injury.
Hill
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NS
Pulmonary Divisions, New England Medical Center, Boston, Massachusetts 01770.
Jederlinic
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Gagnon
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D000818:Animals; D006332:Cardiomegaly / Q000139:chemically induced* / Q000517:prevention & control; D006976:Hypertension, Pulmonary / Q000139:chemically induced* / Q000503:physiopathology; D000860:Hypoxia / Q000503:physiopathology*; D055370:Lung Injury; D008297:Male; D016686:Monocrotaline; D010102:Oxygen Inhalation Therapy; D010947:Plants, Toxic; D011763:Pyrrolizidine Alkaloids / Q000506:poisoning*; D051381:Rats; D011919:Rats, Inbred Strains; D012674:Senecio
D011763:Pyrrolizidine Alkaloids; D016686:Monocrotaline