Allopurinol fails to protect rat diaphragm (dph) from functional impairment during inspiratory resistive loading (IRL)

L. Maxwell, G. Rodney, W. Napier, J. Alkins, A. Anzueto

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Recent studies have linked reactive oxygen species to DPH impairment during IRL (JAP 72:529, 1992; JAP 77:812, 1994). We have previously shown that inhibition of xanthine oxidase (XO) activity with a tungsten diet protects the DPH from the effects of IRL (Chest 104:45, 1993; AJRCCM 151:AS84, 1995). We further tested the involvment of XO in the IRL Induced DPH dysfunction by chronic administration of allopurinol, a competitive inhibitor of XO. Adult male Sprague-Dawley rats (N.24,260-440 g) received allopurinol (10 mg/kg, PO) or distilled water for 7 days. Each group was divided into: 1 (unimpeded breathing (Control, Allopurinol) and 2) breathing through an inspirator/ resistance at 70% of maximal airway pressure until apnea (IRL, Allopurinol+IRL), followed by 15 minutes of mechanical ventilation (MV). After in-vivo protocols, a portion of DPH was removed tor in-vttro contractile properties, including maximum isometric (Po, N/cm2) and twitch (Pt, N/cm2) tensions, and rate of twitch force development (dP/dT, N/cm2/s). Control Allopurinol IRL Allopurlnol+IRL Po 29.1 ± .6 29.5 ± .1.1 22.2±3.1t 21.7±2.6 a Pt 12.7 ±.9 12.0 ±-2 7.8 ± 2-2 5.4 ±.8 dP/dT 634±55 512±58 385 ±87 275± 36 Mean ±SEM, t p≤0.05 vs Control, p≤0.05 vs Control & Allopurinol Inhibition of XO activity with allopurinol prior to IRL does not protect rat DPH function. These results are not consistent with our previous experiments using a tungsten diet to inhibit XO.

Original languageEnglish (US)
Pages (from-to)A3
JournalFASEB Journal
Volume10
Issue number3
StatePublished - Dec 1 1996

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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