HYPOXIA-INDUCED PULMONARY-HYPERTENSION IN AN OPTIMIZED ENVIRONMENT FOR THE GUINEAPIG

Prolonged exposure to hypoxia elicits a variety of time-related morpho logic and physiologic changes in the pulmonary vasculature of mammals, including humans. The study of hypoxia induced changes in rodents gen erally requires a prolonged-exposure to 9% oxygen for a minimum of 10 days in an airtight chamber, which has only been generally described i n the literature as large (200-400 l), sealed acrylic chambers. To ass ist in the search for better therapies for diseases associated with ch ronic hypoxia using animal models, we have custom-built an airtight ch amber for hypoxic exposure of rodents, and characterized the effect of chronic hypoxia on functional and morphologic changes in the pulmonar y vasculature of the guineapig using this system. This chamber has bee n designed to alleviate any unnecessary stress related to food or wate r intake, cleanliness and-excess illumination to the animals during th e hypoxic-exposure period. Chronic exposure of the guineapig to hypoxi a (0-21 days). produced time-related physiologic, morphologic, and hae matologic changes. For example, after 10 days in hypoxia (9% oxygen), pulmonary artery pressure was significantly increased from 13 +/- 1 mm Hg 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 a s 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 cha nges 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 h aematocrit, 48 +/- 0.7 (day 0) to 61 +/- 0.9 (day 10, P < 0.05), and h aemoglobin, 16 +/- 0.2 (day 0) to 20 +/- 0.1 (day 10, P < 0.05). It is concluded that considerations-for the wellbeing of the test animals ( i.e. continuous water, ample food supplies, burrow-like hiding places, sanitation and protection from excess illumination) can easily be inc orporated into a hypoxic chamber. The purpose of the present study was to explore modifications that may provide the animal with an optimize d environment which will reduce anxiety and stress, as seen in their b ehaviour when inside the chambers, and to thoroughly characterize the morphologic and physiologic changes associated with chronic hypoxia wh ich develop in a consistent time-related manner.