Repeated exposure to heat stress results in a diaphragm phenotype that resists ventilator-induced diaphragm dysfunction.

Controlled mechanical ventilation (CMV) is a life-saving intervention for patients in respiratory failure. Unfortunately, prolonged mechanical ventilation (MV) results in diaphragmatic atrophy and contractile dysfunction, both of which are predicted to contribute to problems in weaning patients from the ventilator. Therefore, developing a strategy to protect the diaphragm against ventilator-induced weakness is important. We tested the hypothesis that repeated bouts of heat stress result in diaphragm resistance against CMV-induced atrophy and contractile dysfunction. Male Wistar rats were randomly divided into six experimental groups: 1) control; 2) single bout of whole body heat stress; 3) repeated bouts of whole body heat stress; 4) 12 h CMV; 5) single bout of whole body heat stress 24 h before CMV; and 6) repeated bouts of whole body heat stress 1, 3, and 5 days before 12 h of CMV. Our results revealed that repeated bouts of heat stress resulted in increased levels of heat shock protein 72 in the diaphragm and protection against both CMV-induced diaphragmatic atrophy and contractile dysfunction at submaximal stimulation frequencies. The specific mechanisms responsible for this protection remain unclear: this heat stress-induced protection against CMV-induced diaphragmatic atrophy and weakness may be partially due to reduced diaphragmatic oxidative stress, diminished activation of signal transducer/transcriptional activator-3, lower caspase-3 activation, and decreased autophagy in the diaphragm.