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

L. Maxwell, G. Rodney, W. Napier, J. Alkins, Antonio R Anzueto

Research output: Contribution to journalArticle

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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)
JournalFASEB Journal
Volume10
Issue number3
StatePublished - 1996

Fingerprint

allopurinol
Allopurinol
diaphragm
Diaphragms
Diaphragm
Rats
xanthine oxidase
Xanthine Oxidase
rats
tungsten
Tungsten
Nutrition
breathing
Respiration
Diet
apnea
chest
Apnea
Artificial Respiration
diet

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

Cite this

Allopurinol fails to protect rat diaphragm (dph) from functional impairment during inspiratory resistive loading (IRL). / Maxwell, L.; Rodney, G.; Napier, W.; Alkins, J.; Anzueto, Antonio R.

In: FASEB Journal, Vol. 10, No. 3, 1996.

Research output: Contribution to journalArticle

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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.",
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