Pulmonary vascular adaptations to augmented polycythemia during
chronic hypoxia.
Petit, Raymond D., Rod R. Warburton, Lo-Chang Ou, and Nicholas S.
Hill.
Division of Pulmonary and Critical Care Medicine, Rhode Island
Hospital and Brown University, Providence, Rhode Island, and the
Department of Physiology, Dartmouth Medical School, Hanover, New
Hampshire
APStracts 2:0133A, 1995.
In a prior study, we found that augmentation of polycythemia by
exogenous human recombinant erythropoietin (EPO) failed to worsen the
severity of hypoxic pulmonary hypertension in rats . The present
study sought to determine whether this unexpected finding was related
to reductions in cardiac output, left ventricular end diastolic
pressure, pulmonary vascular resistance, or some combination of these
factors. Four groups of Sprague-Dawley rats were studied over a 3
week period; hypoxic (0.5 atm) and normoxic animals each injected
with EPO (500 Ukg-1sc thrice weekly) (HE and NE rats) or saline (in
controls) (HC and NC rats). As observed previously, we found that
pulmonary artery (PA) pressures and right ventricular hypertrophy
were not increased in EPO-treated rats despite significant increases
in hematocrit and blood viscosity. Cardiac outputs, blood volumes and
left ventricular end diastolic pressures were also similar in EPO
-treated and control rats. Acute changes in PA pressure in response to
acute normoxia in hypoxic rats and acute hypoxia in normoxic rats
were similar in EPO-treated and control groups, suggesting no
differences in vasoreactivity. In addition, EPO treatment had no
effect on pulmonary vascular resistance or structure in normoxic
rats. However, lungs isolated from EPO-treated hypoxic rats had lower
pulmonary vascular resistance than saline-treated hypoxic rats when
perfused with blood from normocythemic donor rats. In addition, PA
medial thickness and the percentage of muscularized small PAs were
significantly lower in EPO-treated compared to control hypoxic rats.
These results indicate that augmented polycythemia fails to worsen
normoxic pulmonary hypertension in rats because of a decrease in the
severity of structural remodeling.
Received 26 October 1994; accepted in final form 20 February
1995.
APS Manuscript Number A1101-4.
Article publication pending Journal of Applied Physiology.
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 4 April 1995.