THE EARLY EFFECTS OF MECHANICAL VENTILATION ON ISOTONIC CONTRACTILE PROPERTIES AND MAF-box GENE EXPRESSION IN THE DIAPHRAGM

This study aimed to determine the time-dependent effects of diaphragmatic inactivity on its maximum shortening velocity (Vmax) and the Muscle Atrophy F-box (MAF-box, atrogin-1) gene expression during controlled mechanical ventilation (CMV). Twenty-four New Zealand White rabbits were grouped into 1 day, 2 days and 3 days of CMV and controls in equal numbers. The in vitro isotonic contractile properties of the diaphragm were determined. In addition, myosin heavy chain protein and mRNA, myosin light chain, MAF-box mRNA, and volume density of abnormal myofibrils were measured. Tetanic force decreased, and Vmax increased from control of 6.4 to 6.6, 7.7 and 8.1 ML/s after 1 day, 2 days and 3 days of CMV, respectively (P< 0.02). The increased Vmax compensated for the decreased tetanic force; consequently, compared to the controls, maximum power output was unchanged after 3 days of CMV. Vmax correlated with the volume density of abnormal myofibrils (y= 0.1x + 5.7 (r = 0.87, P < 0.01)). In the diaphragm, MAF-box was over-expressed (355 % of control) after 1 day of CMV, prior to the evidence of structural myofibril disarray. In conclusion, CMV produced a time-dependent increase in Vmax that was associated with the degree of myofibrillar disarray and independent of changes in myosin isoform expression. Furthermore, CMV produced an increase in MAF-box mRNA levels that may be partially or completely responsible for the degree of myofibrillar disarray resulting from CMV.