Phrenic nerve stimulation protects against mechanical ventilation-induced diaphragm dysfunction in rats

ABSTRACT Introduction: We investigated a novel application of phrenic nerve stimulation (PNS) in diaphragm dysfunction induced by mechanical ventilation (MV). Methods: Twenty‐one Sprague‐Dawley rats were assigned randomly to 3 groups: spontaneous breathing, 18‐h controlled MV, and 18‐h controlled MV with PNS. Upon completion of the experimental protocol, diaphragm contractility, gene expression of insulin‐like growth factor‐1 (IGF‐1) and ubiquitin ligases, and serum IGF‐1 levels were analyzed. Results: Compared with the spontaneously breathing rats, impaired diaphragm contractile function, including force‐related properties and force‐frequency responses, were pronounced with MV. Furthermore, MV suppressed IGF‐1 and induced muscle ring finger 1 mRNA expression in the diaphragm. In contrast, PNS counteracted MV‐induced gene expression changes in the diaphragm and restored diaphragm function. Conclusions: PNS exerted a protective effect against MV‐induced diaphragm dysfunction by counteracting altered expression of IGF‐1 and ubiquitin ligase in the diaphragm. Muscle Nerve 48: 958–962, 2013