N-tert-butyl-[alpha]-phenylnitrone: a free radical trap with unanticipated effects on diaphragm function. Andersen, Katherine A., Philip T. Diaz, Valerie P. Wright, and Thomas L. Clanton. The Ohio State University, College of Medicine, Department of Internal Medicine, Division of Pulmonary and Critical Care
APStracts 2:0476A, 1995.
The spin trap N-tert-butyl-[alpha]-phenylnitrone (PBN) has a high avidity for free-radical species and hence functions as an antioxidant in many biological systems. As such, we hypothesized that PBN would have powerful antioxidant effects on muscle function. We examined the effects of PBN on directly stimulated in vitro (37 C) rat diaphragm. First, a dose response curve for the effects of PBN on force-frequency was established (n = 8) by comparing PBN-treated muscle strips (0.01-10 mM) with time- and stimulus-matched controls. Second, the effect of 1.0 mM PBN on muscle endurance (n = 8) was established. We found that: 1) Compared to baseline, peak twitch and low frequency muscle tensions increased in a dose-dependent fashion, with peak effects at 1.0 mM PBN. 2) Muscle function at all stimulation frequencies was depressed at doses above 1.0 mM PBN. 3) Complete inhibition at 10 mM PBN was reversed with caffeine administration or washout. 4) During early fatigue, 1.0 mM PBN facilitated force. However, endurance time decreased in the PBN -treated group. We conclude that PBN has direct, reversible, dose -dependent effects on diaphragm function. Facilitation of low frequency forces and the lack of fatigue attenuating properties, however, suggests PBN has atypical antioxidant effects on muscle function. 

Received 14 June 1995; accepted in final form 6 October 1995.
APS Manuscript Number A643-5.
Article publication pending Journal of Applied Physiology.
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 6 November 95