Infection induced diaphragm weakness is a major contributor to death and prolonged mechanical ventilation in critically ill patients. Infection induced muscle dysfunction is associated with activation of muscle proteolytic enzymes, and taurine is known to suppress proteolysis. We therefore postulated that taurine administration may prevent infection induced diaphragm dysfunction. The purpose of this study was to test this hypothesis using a clinically relevant animal model of infection, i.e. cecal ligation puncture induced sepsis (CLP). Studies were performed on (n = 5–7 mice/group): (a) sham operated controls, (b) animals with sepsis induced by CLP, (c) sham operated animals given taurine (75 mg/kg/d, intraperitoneally), and (d) CLP animals given taurine. At intervals after surgery animals were euthanized, diaphragm force generation measured in vitro, and diaphragm calpain, caspase and proteasomal activity determined. CLP elicited a large reduction in diaphragm specific force generation at 24 h (1–150 Hz, p < 0.001) and taurine significantly attenuated CLP induced diaphragm weakness at all stimulation frequencies (p < 0.001). CLP induced significant increases in diaphragm calpain, caspase and proteasomal activity; taurine administration prevented increases in the activity of all three pathways. In additional time course experiments, diaphragm force generation remained at control levels over 72 h in CLP animals treated with daily taurine administration, while CLP animals demonstrated severe, sustained reductions in diaphragm strength (p < 0.01 for all time points). Our results indicate that taurine administration prevents infection induced diaphragm weakness and reduces activation of three major proteolytic pathways. Because this agent is has been shown to be safe, non-toxic when administered to humans, taurine may have a role in treating infection induced diaphragm weakness. Future clinical studies will be needed to assess this possibility.
|Journal||Respiratory Physiology and Neurobiology|
|State||Published - Jan 2020|
Bibliographical noteFunding Information:
Dr. Supinski is supported by R01HL113494 and R01HL141356 National Heart, Lung and Blood Institute of the National Institutes of Health and by 5I01BX002132 from the Department of Veterans Affairs . Dr. Callahan is supported by R01HL112085 and R01HL141356 from the National Heart, Lung and Blood Institute of the National Institutes of Health . Dr. Schroder is supported by R01HL141356 from the National Heart, Lung and Blood Institute of the National Institutes of Health .
© 2019 Elsevier B.V.
- Diaphragm force generation
- Diaphragm weakness
ASJC Scopus subject areas
- Neuroscience (all)
- Pulmonary and Respiratory Medicine