Induced hypothermia is protective in a rat model of pneumococcal pneumonia associated with increased adenosine triphosphate availability and turnover*

Abstract

Objective: To determine the effect of induced hypothermia on bacterial growth, lung injury, and mitochondrial function in a rat model of pneumococcal pneumosepsis.

Design: Animal study.

Setting: University research laboratory.

Subjects: Male Sprague-Dawley rats.

Interventions: Subjects were inoculated intratracheally with Streptococcus pneumoniae and controls received saline. After the development of pneumonia, mechanical ventilation was started with or without induced mild hypothermia (32 °C). Bacterial growth and inflammatory markers were determined in bronchoalveolar lavage fluid, blood, and organs. Oxidative phosphorylation and adenosine triphosphate contents were measured in mitochondria isolated from the liver and soleus muscle.

Measurements and main results: Inoculation with S. pneumoniae resulted in severe pneumonia with bacterial dissemination, distal organ injury, and blunted peripheral oxygen consumption on mechanical ventilation. Hypothermia did not affect bacterial growth in bronchoalveolar lavage fluid and in homogenized lungs compared with normothermic controls but was associated with reduced bacterial dissemination to the spleen with a trend toward reduced bacterial load in blood and liver. Hypothermia reduced lung injury, exemplified by reductions in pulmonary cell influx and bronchoalveolar lavage fluid protein levels compared with controls. Hypothermia reduced bronchoalveolar lavage fluid levels of interleukin-1β, tended to reduce bronchoalveolar lavage fluid CINC-3 levels, but no effect was observed on bronchoalveolar lavage fluid tumor necrosis factor-α and interleukin-6 levels. Induced hypothermia restored the fall in oxygen consumption and adenosine triphosphate levels in the liver, whereas adenosine triphosphate/adenosine diphosphate ratios remained low. In muscle, induced hypothermia also reversed low oxygen consumption as a result of pneumonia, but with an increase in adenosine triphosphate levels, whereas adenosine triphosphate/adenosine diphosphate ratios were low.

Conclusion: Hypothermia did not adversely affect bacterial growth, but rather reduced bacterial dissemination in a rat model of pneumococcal pneumosepsis. Furthermore, hypothermia reduced lung injury associated with restored adenosine triphosphate availability and turnover. These findings suggest that hypothermia may reduce organ injury by preventing sepsis-related mitochondrial dysfunction.