Am. J. Respir. Crit. Care Med., Volume 156, Number 5, November 1997, 1567-1571

Effect of N-Acetylcysteine on Human Diaphragm Strength and Fatigability

JOHN M. TRAVALINE, SHRIVAS SUDARSHAN, BRUCE G. ROY, FRANCIS CORDOVA, VADIM LEYENSON, and GERARD J. CRINER

Division of Pulmonary and Critical Care Medicine, Department of Medicine, Temple University School of Medicine, Philadelphia, Pennsylvania

Free radical injury is believed to be important in diaphragm dysfunction. N-Acetylcysteine (NAC) is a potent free radical scavenger shown in animal models to attenuate diaphragm fatigue; however, its effects on human diaphragm function are unknown. We assessed diaphragm function by electrophrenic twitch stimulation (Pdi_T) and twitch occlusion (to yield Pdi_max) in four healthy subjects 35 ± 3 yr of age (mean ± SD). We intravenously administered NAC (150 mg/kg in 250 ml D₅W) or placebo (CON) (250 ml D₅W) in a randomized manner after subjects were premedicated with antihistamines. There were no significant side effects with the infusion. After infusion, we measured baseline Pdi_max and Pdi_T at FRC. Diaphragm fatigue was then induced by subjects breathing through an inspiratory resistive load. Pdi_max and Pdi_T were then measured at 15 to 30 min and 1, 2, 3, 4, and 20-25 h after fatigue. Times to fatigue were 13 ± 4 min (CON) and 21 ± 6 min (NAC) (p = 0.04). At 15 min after fatigue, Pdi_T was reduced to 40% (CON) compared with 30% (NAC) initial Pdi_T value (p = 0.05). Other twitch characteristics (maximal rate of relaxation and maximal contraction rate) were reduced to a greater degree after placebo compared with NAC. There were no significant differences in the rate of recovery between CON and NAC. Pdi_max at 30 min after fatigue was significantly greater with NAC; however, at 1 h after fatigue, Pdi_max for CON and NAC were not different, suggesting similar rates of recovery in high-frequency fatigue. These data suggest that NAC may attenuate low-frequency human diaphragm fatigue.

This article has been cited by other articles:

				S. K. Powers and M. J. Jackson Exercise-Induced Oxidative Stress: Cellular Mechanisms and Impact on Muscle Force Production Physiol Rev, October 1, 2008; 88(4): 1243 - 1276. [Abstract] [Full Text] [PDF]

				L. F. Ferreira and M. B. Reid Muscle-derived ROS and thiol regulation in muscle fatigue J Appl Physiol, March 1, 2008; 104(3): 853 - 860. [Abstract] [Full Text] [PDF]

				C. A. C. Ottenheijm, L. M. A. Heunks, and P. N. R. Dekhuijzen Diaphragm Muscle Fiber Dysfunction in Chronic Obstructive Pulmonary Disease: Toward a Pathophysiological Concept Am. J. Respir. Crit. Care Med., June 15, 2007; 175(12): 1233 - 1240. [Abstract] [Full Text] [PDF]

				J. D. Pierce, C. Goodyear-Bruch, S. Hall, and R. L. Clancy Effect of dopamine on rat diaphragm apoptosis and muscle performance Exp Physiol, July 1, 2006; 91(4): 731 - 740. [Abstract] [Full Text] [PDF]

				E. Barreiro, J. B. Galdiz, M. Marinan, F. J. Alvarez, S. N. A. Hussain, J. Gea, and on behalf of the ENIGMA in COPD project Respiratory loading intensity and diaphragm oxidative stress: N-acetyl-cysteine effects J Appl Physiol, February 1, 2006; 100(2): 555 - 563. [Abstract] [Full Text] [PDF]

				A. Couillard and C. Prefaut From muscle disuse to myopathy in COPD: potential contribution of oxidative stress Eur. Respir. J., October 1, 2005; 26(4): 703 - 719. [Abstract] [Full Text] [PDF]

				I. Medved, M. J. Brown, A. R. Bjorksten, K. T. Murphy, A. C. Petersen, S. Sostaric, X. Gong, and M. J. McKenna N-acetylcysteine enhances muscle cysteine and glutathione availability and attenuates fatigue during prolonged exercise in endurance-trained individuals J Appl Physiol, October 1, 2004; 97(4): 1477 - 1485. [Abstract] [Full Text] [PDF]

				I. Medved, M. J. Brown, A. R. Bjorksten, and M. J. McKenna Effects of intravenous N-acetylcysteine infusion on time to fatigue and potassium regulation during prolonged cycling exercise J Appl Physiol, January 1, 2004; 96(1): 211 - 217. [Abstract] [Full Text] [PDF]

				F. Laghi and M. J. Tobin Disorders of the Respiratory Muscles Am. J. Respir. Crit. Care Med., July 1, 2003; 168(1): 10 - 48. [Abstract] [Full Text] [PDF]

				A. Couillard, F. Maltais, D. Saey, R. Debigare, A. Michaud, C. Koechlin, P. LeBlanc, and C. Prefaut Exercise-induced Quadriceps Oxidative Stress and Peripheral Muscle Dysfunction in Patients with Chronic Obstructive Pulmonary Disease Am. J. Respir. Crit. Care Med., June 15, 2003; 167(12): 1664 - 1669. [Abstract] [Full Text] [PDF]

				I. Medved, M. J. Brown, A. R. Bjorksten, J. A. Leppik, S. Sostaric, and M. J. McKenna N-acetylcysteine infusion alters blood redox status but not time to fatigue during intense exercise in humans J Appl Physiol, April 1, 2003; 94(4): 1572 - 1582. [Abstract] [Full Text] [PDF]

				J. D. Pierce, R. L. Clancy, N. Smith-Blair, and R. Kraft Treatment and Prevention of Diaphragm Fatigue Using Low-Dose Dopamine Biol Res Nurs, January 1, 2002; 3(3): 140 - 149. [Abstract] [PDF]

				J. S. Coombes, S. K. Powers, B. Rowell, K. L. Hamilton, S. L. Dodd, R. A. Shanely, C. K. Sen, and L. Packer Effects of vitamin E and {alpha}-lipoic acid on skeletal muscle contractile properties J Appl Physiol, April 1, 2001; 90(4): 1424 - 1430. [Abstract] [Full Text] [PDF]

				M. B. Reid Plasticity in Skeletal, Cardiac, and Smooth Muscle: Invited Review: Redox modulation of skeletal muscle contraction: what we know and what we don't J Appl Physiol, February 1, 2001; 90(2): 724 - 731. [Abstract] [Full Text] [PDF]

				N. FUJIMURA, S. SUMITA, M. AIMONO, Y. MASUDA, Y. SHICHINOHE, E. NARIMATSU, and A. NAMIKI Effect of Free Radical Scavengers on Diaphragmatic Contractility in Septic Peritonitis Am. J. Respir. Crit. Care Med., December 1, 2000; 162(6): 2159 - 2165. [Abstract] [Full Text]

				L. M A Heunks and P N R. Dekhuijzen Respiratory muscle function and free radicals: from cell to COPD Thorax, August 1, 2000; 55(8): 704 - 716. [Full Text]

				L. M. A. Heunks, A. Bast, C. L. A. van Herwaarden, G. R. M. M. Haenen, and P. N. R. Dekhuijzen Effects of emphysema and training on glutathione oxidation in the hamster diaphragm J Appl Physiol, June 1, 2000; 88(6): 2054 - 2061. [Abstract] [Full Text] [PDF]

				G. Supinski, D. Nethery, D. Stofan, and A. DiMarco Extracellular calcium modulates generation of reactive oxygen species by the contracting diaphragm J Appl Physiol, December 1, 1999; 87(6): 2177 - 2185. [Abstract] [Full Text] [PDF]

				T. L. Clanton, L. Zuo, and P. Klawitter Oxidants and Skeletal Muscle Function: Physiologic and Pathophysiologic Implications Experimental Biology and Medicine, December 1, 1999; 222(3): 253 - 262. [Abstract] [Full Text]

				L. C. Lands, V. L. Grey, and A. A. Smountas Effect of supplementation with a cysteine donor on muscular performance J Appl Physiol, October 1, 1999; 87(4): 1381 - 1385. [Abstract] [Full Text] [PDF]

				G. Supinski, D. Nethery, D. Stofan, L. Szweda, and A. DiMarco Oxypurinol administration fails to prevent free radical-mediated lipid peroxidation during loaded breathing J Appl Physiol, September 1, 1999; 87(3): 1123 - 1131. [Abstract] [Full Text] [PDF]