Electrical stimulation of the diaphragm may counteract muscle degradation during prolonged mechanical ventilation: A pilot study using transcriptome analyses

Abstract 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 aimed to evaluate the effects of electrical stimulation of the diaphragm muscle 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. Those 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 improving mitochondrial respiration.