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This Article Full Text Full Text (PDF) All Versions of this Article: 91/4/731    most recent expphysiol.2006.033316v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Pierce, J. D. Articles by Clancy, R. L. Search for Related Content PubMed PubMed Citation Articles by Pierce, J. D. Articles by Clancy, R. L. Related Collections Muscle

¹ School of Nursing² Department of Molecular and Integrative Physiology³ School of Allied Health, Nurse Anaesthesia⁴Department of Preventive Medicine and Public Health⁵ Department of Molecular and Integrative Physiology, University of Kansas Medical Center, 3901 Rainbow Blvd, Kansas City, KS 66160-7504, USA

The purpose of this study was to determine whether dopamine (DA) decreases diaphragm apoptosis and attenuates the decline in diaphragmatic contractile performance associated with repetitive isometric contraction using an in vitro diaphragm preparation. Strenuous diaphragm contractions produce free radicals and muscle apoptosis. Dopamine is a free radical scavenger and, at higher concentrations, increases muscle contractility by simulating ß₂-adrenoreceptors. A total of 47 male Sprague–Dawley rats weighing 330–450 g were used in a prospective, randomized, controlled in vitro study. Following animal anaesthetization, diaphragms were excised, and muscle strips prepared and placed in a temperature-controlled isolated tissue bath containing Krebs–Ringer solution (KR) or KR plus 100 µM DA. The solutions were equilibrated with oxygen (O₂) at 10, 21 or 95% and 5% carbon dioxide, with the balance being nitrogen. Diaphragm isometric twitch and subtetanic contractions were measured intermittently over 65 min. The diaphragms were then removed and, using a nuclear differential dye uptake method, the percentages of normal, apoptotic and necrotic nuclei were determined using fluorescent microscopy. There were significantly fewer apoptotic nuclei in the DA group diaphragms than in the KR-only group diaphragms in 10 and 21% O₂ following either twitch or subtetanic contractions. Dopamine at 100 µM produced only modest increases in muscle performance in both 10 and 21% O₂. The attenuation of apoptosis by DA was markedly greater than the effect of DA on muscle performance. Dopamine decreased diaphragmatic apoptosis, perhaps by preventing the activation of intricate apoptotic pathways, stimulating antiapoptotic mechanisms and/or scavenging free radicals.

(Received 25 January 2006; accepted after revision 25 March 2006; first published online 27 April 2006)
Corresponding author J. D. Pierce: University of Kansas Medical Center, School of Nursing, 3901 Rainbow Blvd, Mail stop no. 4043, Kansas City, KS 66160, USA. Email: jpierce{at}kumc.edu

This article has been cited by other articles:

				C. A. Goodyear-Bruch, J. Jegathesan, R. L. Clancy, and J. D. Pierce Apoptotic-Related Protein Expression in the Diaphragm and the Effect of Dopamine During Inspiratory Resistance Loading Biol Res Nurs, April 1, 2008; 9(4): 293 - 300. [Abstract] [PDF]