Detrimental Effects of Short-term Mechanical Ventilation on Diaphragm Function and IGF-I MRNA in Rats

Objectives: Because respiratory muscle weakness appears to play an important role in weaning from mechanical ventilation, we developed an animal model of mechanical ventilation with appropriate controls in order to determine whether 24 h of mechanical ventilation already affected diaphragmatic function.

Design And Interventions: Fifty-two male Wistar rats were randomized into three groups: a non-anesthetized control group (C, n=10), an anesthetized spontaneously breathing group (SB, n=9 out of 26), and an anesthetized and mechanically ventilated group (MV, n=12 out of 16).

Results: After 24 h, in vitro diaphragmatic force was decreased in SB group but even more so in MV group (i.e., 80 Hz: -15% in SB, P<0.005 vs C and -34% in MV group, P<0.005 vs C and SB). This was associated with a significant decrease in the diaphragm type I and type IIa dimensions in the SB group, which was more pronounced in the MV group. Interestingly, diaphragm IGF-I mRNA was decreased in the SB group (-14%, P<0.05 vs C), but more so in MV group (-29%, P<0.001 vs C and P<0.01 vs SB). Moreover, there was a significant correlation between diaphragm force and IGF-I mRNA (at 80 Hz r=0.51, P=0.0056).

Conclusions: We conclude that 24 h of mechanical ventilation in rats, independently of anesthesia, already significantly reduced diaphragm force, fiber dimensions, and its IGF-I mRNA levels.