title: The effects of pentoxifylline on skeletal muscle contractility and neuromuscular transmission during hypoxia.
abstract: OBJECTIVE
  The objective of this study was to investigate the effects of pentoxifylline (PTX), a drug that is mainly used for indications related to tissue hypoxia, on hypoxia-induced inhibition of skeletal muscle contractility and neuromuscular transmission in mice. We hypothesized that chronic PTX treatment alters skeletal muscle contractility and hypoxia-induced dysfunction.
  
  
  METHODS
  Mice were treated with 50 mg/kg PTX or saline intraperitoneally for a week. Following ether anesthesia, diaphragm muscles were removed; isometric muscle contractions and action potentials were recorded. Time to reach neuromuscular blockade and the rate of recovery of muscle contractility were assessed during hypoxia and re-oxygenation.
  
  
  RESULTS
  The PTX group displayed 90% greater twitch amplitudes (P < 0.01). Hypoxia depressed twitch contractions and caused neuromuscular blockade in both groups. However, neuromuscular blockade occurred earlier in PTX-treated animals (P < 0.05). Muscle contractures developed during hypoxia were more pronounced in the PTX group (P < 0.05). Re-oxygenation reduced contracture and indirect muscle contractions resumed. The rate of recovery of contractions was faster (P < 0.05) and the amplitude of contractions was greater (P < 0.01) in the PTX group. PTX treatment increased amplitude (P < 0.05) and shortened action potential (P < 0.05) without altering resting membrane potential, excitation threshold, and neurotransmitter release.
  
  
  CONCLUSIONS
  Chronic PTX treatment increases diaphragm contractility, but amplifies hypoxia-induced contractile dysfunction in mice. These results may implicate important clinical consequences for clinical usage of PTX in hypoxia-related conditions.
authors.affiliation: Department of Physiology, Faculty of Medicine, Hacettepe University, 06100 Sihhiye, Ankara, Turkey.
authors.forename: Fatma
authors.initials: F
authors.lastname: Simsek-Duran
authors.forename: Mert
authors.initials: M
authors.lastname: Ertunc
authors.forename: Rustu
authors.initials: R
authors.lastname: Onur