Zidovudine (AZT)-induced diaphragmatic contractile dysfunction

R. A. Herb, A. M. Maxwell, J. K. Stears, J. Frisbie, S. Ristow, L. Mieding, Richard J Coast

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Abstract

Numerous reports indicate a unique, drug-induced striated muscle myupathy associated with zidovudine (AXT) administration. To date however, the impact of AZT on respiratory muscle contractile function is unknown. To test the hypothesis that AZT administration would reduce normalized specific force production (specific Po) and fatigue resistance, costal diaphragm strips from control (n =6) and AZT-treated (n =6) female, Sprague-Dawley rats were studied utilizing an in vitro muscle preparation. Animals were administered AZT (IP; 20mg/kg/day) or saline (CON) over a 6 week experimental period. Maximal diaphragmatic specific Po of AZT-treated animals (24.9 N/cm2) were significantly (p<0.01) reduced when compared to the CON group (30.1 N/cm2). Further, following a 30 min fatigue protocol, diaphragmatic fatiguability was significantly (p<0.05) increased in the AZT group. These data indicate that AZT treatment induces diaphragmatic contractile dysfunction which may exacerbate clinical pulmonary complications associated with AIDS infection. Future studies will be necessary to elucidate the mechanisim(s) responsible for the observed reductions in diaphragmatic fatigue resistance and force development. Funded by NAU Organized Research.

Original languageEnglish (US)
JournalFASEB Journal
Volume11
Issue number3
StatePublished - 1997

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ASJC Scopus subject areas

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

Cite this

Herb, R. A., Maxwell, A. M., Stears, J. K., Frisbie, J., Ristow, S., Mieding, L., & Coast, R. J. (1997). Zidovudine (AZT)-induced diaphragmatic contractile dysfunction. FASEB Journal, 11(3).