# Effects of a Three-Day vs. Six-Day Exposure to Normobaric Hypoxia on the Cardiopulmonary Function of Rats

## TL;DR

Exposing rats to hypoxia for six days worsens heart and lung function compared to three days, leading to higher stress and early deaths.

## Contribution

This study reveals that prolonged hypoxia worsens cardiopulmonary function in rats, contradicting expectations of acclimatization.

## Key findings

- Prolonged hypoxia worsens left ventricular function and increases right ventricular pressure in rats.
- Pulmonary edema and inflammation persist and worsen with extended hypoxia exposure.
- Six-day hypoxia exposure leads to a 33% premature death rate in rats.

## Abstract

In rats, normobaric hypoxia significantly reduced left ventricular (LV) inotropic function while right ventricular (RV) function was not impaired. In parallel, the animals developed pulmonary edema and inflammation. In the present study, we investigated whether cardiac function and pulmonary injury would aggravate after three and six days of hypoxia exposure or whether cardiopulmonary reactions to prolonged hypoxia would become weaker due to hypoxic acclimatization. Sixty-four female rats were exposed for 72 or 144 h to normoxia. They received a low-rate infusion (0.1 mL/h) with 0.9% NaCl solution. We evaluated indicators of the general condition, blood gas parameters, and hemodynamic function of the rats. In addition, we performed histological and immunohistochemical analyses of the lung. Despite a significant increase in hemoglobin concentration, the LV function deteriorated with prolonged hypoxia. In contrast, the RV systolic pressure and contractility steadily increased by six days of hypoxia. The pulmonary edema and inflammation persisted and rather increased with prolonged hypoxia. Furthermore, elevated protein concentration in the pleural fluid indicated capillary wall stress, which may have aggravated the pulmonary edema. In conclusion, six days of hypoxia and NaCl infusion place significant stress on the cardiopulmonary system of rats, as is also reflected by the 33% of premature deaths in this rat group.