Molecular response of the human diaphragm on different modes of mechanical ventilation.

BACKGROUND The mechanical stress that the human diaphragm is exposed to during mechanical ventilation affects a variety of processes, including signal transduction, gene expression, and angiogenesis. OBJECTIVES The study aim was to assess the change in the production of major angiogenic regulators [vascular endothelial growth factor (VEGF), fibroblast growth factor-2 (FGF2), and transforming growth factor beta 1 (TGFB1)] on the human diaphragm before and after contraction/relaxation cycles during mechanical ventilation. METHODS This observational study investigates the diaphragmatic mRNA expression of VEGF, FGF2, and TGFB1 in surgical patients receiving general anesthesia with controlled mechanical ventilation (CMV) with muscle relaxation (group A, n = 13), CMV without muscle relaxation (group B, n = 10), and pressure support of spontaneous breathing (group C, n = 9). Diaphragmatic samples were obtained from each patient at two time points: 30 min after the induction of anesthesia (t1) and 90 min after the first specimen collection (t2). RESULTS No significant changes in the mRNA expression of VEGF, FGF2, and TGFB1 were documented in groups A and C between time points t1 and t2. In contrast, in group B, the mRNA levels of the above angiogenic factors were increased in time point t2 compared to t1, a finding which was statistically significant (pVEGF = 0.003, pFGF2 = 0.028, pTGFB1 = 0.001). CONCLUSIONS These findings suggest that the molecular response of the human diaphragm before and after application of diverse modes of mechanical ventilation is different. Angiogenesis via the expression of VEGF, FGF2, and TGFB1 was only promoted in CMV without muscle relaxation, and this may have important clinical implications.