Grant: Operating Grant

Patients with respiratory failure from different causes often require temporary respiratory support by a breathing machine (ventilator), a treatment known as mechanical ventilation. Unfortunately, mechanical ventilation itself has many side effects, and this includes the development of respiratory muscle (especially diaphragm) weakness. Once the diaphragm is weak, it becomes very difficult to remove patients from the ventilator. This proposal will investigate the role of abnormal mitochondrial function in causing this problem. Mitochondria are the major energy generators within the cell, and can also be the source of harmful substances such as damaging free radicals. We will study diaphragm samples obtained from genetically altered and drug-treated mice, as well as humans who received mechanical ventilation prior to death. These studies will provide new information about the cellular mechanisms linking mitochondrial dysfunction to diaphragmatic weakness in mechanically ventilated patients, which is a very commonly encountered clinical problem.