Influence of weaning modes on diaphragmatic remodeling in an animal model of ventilator-induced diaphragmatic dysfunction

• Applicant: Professor Dr. Rolf Rossaint
• Subject Area: Anaesthesiology
• Term: from 2012 to 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 221808144

Mechanical ventilation (MV) is a life saving intervention in patients with respiratory failure. Ventilatory support time can last for weeks while the diaphragm is inactive or only partially active. Previous studies involving animals and humans demonstrate the rapid muscle atrophy associated with MV. Partial activation of the diaphragm reduces atrophy but does not prevent it completely. To our knowledge, all studies examining diaphragmatic activation did not mimic an already atrophic diaphragm and/or pre-existent injury prior to MV, although this is common in intensive care units. Therefore, the proposed experiments will examine the influence of weaning modes on the regeneration of a pre-injured or healthy diaphragmatic muscle that underwent 12 h of mechanical ventilation. Two experimental settings will investigate either healthy rats or rats with lung emphysema. Latter animals establish a differing diaphragmatic texture due to long term resistive breathing over several months. All animals will be assigned to experimental groups undergoing MV to induce diaphragmatic atrophy, after which the diaphragm will be reloaded either directly or stepwise. Changes in atrophy, myogenesis and cell damage will be investigated. Due to the fact that neuromuscular blocking agents aggravate the pathohphysiology occurring during MV, these processes will be tested in the experimental setting that uses healthy animals. Overall results will provide insight in the effectiveness of weaning modalities, especially under the consideration of an ICU setting with additional comorbidities and potentially harmful drug use .

• DFG Programme: Research Grants
• Participating Person: Privatdozent Dr. Christian Brülls