Hypoxia-induced pulmonary hypertension in an optimized environment for the guineapig

Abstract

Prolonged exposure to hypoxia elicits a variety of time-related morphologic and physiologic changes in the pulmonary vasculature of mammals, including humans. The study of hypoxia-induced changes in rodents generally requires a prolonged exposure to 9% oxygen for a minimum of 10 days in an airtight chamber, which has only been generally described in the literature as large (200-400 l), sealed acrylic chambers. To assist in the search for better therapies for diseases associated with chronic hypoxia using animal models, we have custom-built an airtight chamber for hypoxic exposure of rodents, and characterized the effect of chronic hypoxia on functional and morphologic changes in the pulmonary vasculature of the guineapig using this system. This chamber has been designed to alleviate any unnecessary stress related to food or water intake, cleanliness and excess illumination to the animals during the hypoxic-exposure period. Chronic exposure of the guineapig to hypoxia (0-21 days) produced time-related physiologic, morphologic, and haematologic changes. For example, after 10 days in hypoxia (9% oxygen), pulmonary artery pressure was significantly increased from 13±1 mmHg in normoxic controls (day 0, n=6) to 26±0 mmHg (day 10, n=4, P<0.01). Right ventricular hypertrophy in hypoxic animals, presented as a ratio of right ventricle free wall weight to body weight, showed a significant increase from 0.054±0.004 (day 0) to 0.069±0.004 on day 10 ( P<0.05), while age-matched normoxic animals showed no changes in right ventricular weight (day 0=0.059; day 10=0.058; P>0.05). Red blood cell count significantly increased over the same time period, from 5.9±0.1 (day 0) to 6.4±0.1 (day 10, P<0.05) as did haematocrit, 48±0.7 (day 0) to 61±0.9 (day 10, P<0.05) and haemoglobin, l6±0.2 (day 0) to 20±0.1 (day 10, P<0.05). It is concluded that considerations for the well-being of the test animals (i.e. continuous water, ample food supplies, burrow-like hiding places, sanitation and protection from excess illumination) can easily be incorporated into a hypoxic chamber. The purpose of the present study was to explore modifications that may provide the animal with an optimized environment which will reduce anxiety and stress, as seen in their behaviour when inside the chambers, and to thoroughly characterize the morphologic and physiologic changes associated with chronic hypoxia which develop in a consistent time-related manner.