Electrical Stimulation Mitigates Muscle Degradation Shift in Gene Expressions during 12-hour Mechanical Ventilation

Ventilator-induced diaphragm dysfunction (VIDD), a dysfunction of the diaphragm muscle caused by prolonged mechanical ventilation (MV), is an important factor that hinders successful weaning from ventilation. We evaluated the effects of electrical stimulation of the diaphragm muscle (pulsed current with off-time intervals) on genetic changes during 12 hours of MV (E-V12). Rats were divided into four groups: control, 12-hour MV, sham operation, and E-V12 groups. Transcriptome analysis using an RNA microarray revealed that 12-hour MV caused upregulation of genes promoting muscle atrophy and downregulation of genes facilitating muscle synthesis, suggesting that 12-hour MV is a reasonable method for establishing a VIDD rat model. Of the genes upregulated by 12-hour MV, 18 genes were not affected by the sham operation but were downregulated by E-V12. These included genes related to catabolic processes, inflammatory cytokines, and skeletal muscle homeostasis. Of the genes downregulated by 12-hour MV, 6 genes were not affected by the sham operation but were upregulated by E-V12. These included genes related to oxygen transport and mitochondrial respiration. These results suggested that 12-hour MV shifted gene expression in the diaphragm muscle toward muscle degradation and that electrical stimulation counteracted this shift by suppressing catabolic processes and increasing mitochondrial respiration. The study involved 16 rats divided into four groups (CON, V12, S-V12, E-V12): Control (CON): Rats not subjected to ventilation, diaphragm harvested after anesthesia. Ventilatory management (V12): Rats with tracheostomy, mechanically ventilated for 12 hours. Sham operation (S-V12): Rats with tracheostomy and abdominal incision, no electrical stimulation applied during 12 hours of mechanical ventilation. Ventilatory management and electrical stimulation (E-V12): Rats with tracheostomy and abdominal incision, continuous electrical stimulation applied during 12 hours of mechanical ventilation with diaphragmatic contraction monitoring. Transcriptome analysis of the diaphragm was performed using the Clariom S Assays Array.