Endocrine changes in a rat model of chronic hypoxia mimicking cyanotic heart disease.

Objective: The endocrine system plays an important role in the adaptation to hypoxia. The aim of this study is to assess the effect of chronic hypoxia on endocrine changes in a neonatal animal model mimicking cyanotic heart disease.

Methods: Sprague-Dawley rats were placed in a normobaric hypoxic environment at birth and oxygen levels were maintained at 10% in an airtight Plexiglas chamber. Controls remained in room air. Animals were sacrificed at 4 and 8 weeks of life. Hematocrit, Free T4 (FT4), Thyrotropin (TSH), corticosterone, and Growth hormone (GH) were measured.

Results: Significant polycythemia developed in the hypoxic rats. Free T4 levels were significantly lower in the hypoxic (H) group compared to the control (C) group at 4 and 8 weeks with FT4 of 2.44 +/- 1.11 ng/dL (H) and 4.35 +/- 1.62 (C) at 4 weeks with a p value < 0.005 and FT4 of 2.01 +/- 0.36 (H) and 3.25 +/- 0.54 (C) ng/dL at 8 weeks with p < 0.01. At 8 weeks TSH levels were significantly lower in the hypoxic group (1.84 +/- 0.9 ng/mL (H) vs. 3.11 +/- 1.1 (C)) with p < 0.05. Corticosterone levels were higher in the hypoxic group with values of 126 +/- 14.8 ng/mL (H) and 114.1 +/- 12.6 (H) at 4 and 8 weeks respectively, when compared to the control group with values of 82.9 +/- 18.1 (C) and 92.7 +/- 10.3 (C) and 4 and 8 weeks with p < 0.0005 and < 0.05 respectively. Growth hormone levels were lower in the hypoxic group at 4 and 8 weeks with p < 0.05 and p < 0.001, respectively.

Conclusion: Chronic hypoxia in our neonatal rat model was associated with decrease in growth hormone levels and an increase in corticosterone levels. Furthermore, hypoxia resulted in thyroid hormone axis suppression. This effect seems to centrally mediated.