Sepsis results in respiratory failure requiring mechanical ventilation. Inducible nitric oxide synthase (iNOS) production increases in diaphragm from LPS-stimulated animals. We hypothesized that nitric oxide (NO) was responsible for the loss of force production in diaphragm contractile fibers, and that blocking the action of NOS in diaphragm strips from LPS-stimulated animals would augment contractile function.
PURPOSE: To determine whether NOS blockade in LPS-stimulated diaphragm results in increased force production, reduced fatigue, or improved recovery from fatigue.
METHODS AND RESULTS: Diaphragm strips were harvested from control or from guinea pigs18 hours after receiving intraperitoneal E.coli LPS. The strips were mounted between clamps and force transducers suspended in tissue baths. Optimal length and force-frequency curves were established and data were recorded by polygraph. Each run included control strips and strips exposed to the NOS blocker N-w-Nitro-L-Arginine (NLA). Experimental diaphragm strips were incubated with 10mM NLA and fatigued by 10 serial stimulations. Strips were washed and recovery of F was assessed for 30 minutes. Data were evaluated as F (g/cm2) and relative change in force produced. LPS(n=9) and LPS+NLA(n=10) showed a significant (p<0.05) left shift of the force-frequency curve. There was no difference in the rate or extent of fatigue or recovery between NLA(n=8) and control(n=9), or LPS and NLA+LPS. Given this lack of difference, all non-LPS strips were compared to all LPS(non-NLA and NLA) strips, and showed a statistically significant (p<0.001) increase in the initial rate of fatigue but no difference in extent of fatigue.
CONCLUSION: NOS blockade does not alter force, fatigue or recovery in diaphragm, but LPS stimulation shifts the force-frequency relationship to the left and increases the initial rate of diaphragm fatigue without altering the extent of diaphragm fatigue.
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Takano, J., Grange, R. & Levin, D. NITRIC OXIDE SYNTHESIS BLOCKADE DOES NOT ALTER FORCE PRODUCTION IN LPS-STIMULATED OR CONTROL GUINEA PIG DIAPHRAGM STRIPS, BUT LPS STIMULATION INCREASES THE RATE OF FATIGUE • 311. Pediatr Res 39, 54 (1996). https://doi.org/10.1203/00006450-199604001-00331