The effects of pentoxifylline on skeletal muscle contractility and neuromuscular transmission during hypoxia


Simsek-Duran F., Ertunc M., Onur R.

INDIAN JOURNAL OF PHARMACOLOGY, cilt.41, sa.5, ss.213-217, 2009 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 41 Sayı: 5
  • Basım Tarihi: 2009
  • Doi Numarası: 10.4103/0253-7613.58509
  • Dergi Adı: INDIAN JOURNAL OF PHARMACOLOGY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.213-217
  • Anahtar Kelimeler: Contractility, hypoxia, neuromuscular transmission, pentoxifylline, NITRIC-OXIDE, TNF-ALPHA, FATIGUE, CYTOKINES, PROTEASES, RELEASE, INJURY, CAMP, CA2+, NO
  • Hacettepe Üniversitesi Adresli: Evet

Özet

Objectives : 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. Materials and 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. Conclusion : 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.