Differences in Lung and Right Ventricle Responses to Sustained and Intermittent Hypoxia

Abstract

Sustained hypoxia (SH) induces pulmonary arterial hypertension, a model of right heart failure. Intermittent Hypoxia (IH) induces both pulmonary and systemic arterial hypertension and is a model of arterial hypoxemia accompanying occlusive sleep apnea. Our long‐term goal is to capitalize on differences between these two models to dissect out the pathophysiological mechanisms that regulate lung and heart function. We hypothesized that sustained and intermittent hypoxia would differentially alter lung and heart structure and function. We collected left ventricle (LV), right ventricle (RV), and lung tissue from three groups of rats subjected to 7 days of a) SH (n=12); b) IH (n=12); and c) normoxic controls (n=18). The lung to body weight ratios were increased in the SH group compared to the normoxic and IH groups (7.03±0.31 mg/g vs 4.72±0.14 mg/g and 4.74±0.16 mg/g, respectively (p<0.05 for SH compared to both normoxic and IH groups). The RV to body ratios were also increased in the SH group compared to the normoxic and IH groups (0.47±0.01 mg/g vs 0.32±0.01 mg/g and 0.36±0.01 mg/g, respectively (p <0.05 for SH compared to both normoxic and IH groups). The increase in the lung and RV masses indicates fluid accumulation in these organs, consistent with pulmonary hypertension and right heart dysfunction. The LV to body weight ratios were similar among the groups (2.35±0.07 mg/g for the SH; 2.29±0.03 mg/g for the normoxia, and 2.22±0.04 mg/g for the IH; p=ns). Our results show that the two models display different responses in terms of increases in organ weights. We can now use these tissues to explore changes in extracellular matrix composition to determine if early gene changes can be delineated in the two types of hypoxia.