Received January 25, 2006
Revised February 22, 2006
Accepted after revision April 25, 2006

¹ University of Kansas Medical Center

^* To whom correspondence should be addressed. E-mail: jpierce{at}kumc.edu.

	Abstract

The purpose of this study was to determine if dopamine (DA) decreases diaphragm apoptosis and attenuate the decline in diaphragmatic contractile performance associated with repetitive isometric contractions using an in-vitro diaphragm preparation. Strenuous diaphragm contractions produce free radicals and muscle apoptosis. DA is a free radical scavenger and at higher concentrations increases muscle contractility by simulating 2 adrenoreceptors. At the University research laboratory, a total of 47 male Sprague-Dawley rats weighing 330-450 g were used in a prospective, randomized, controlled in-vitro study. Following animal anesthetization, diaphragms were excised, muscle strips prepared and placed in a temperature controlled isolated tissue bath containing Kreb (KR) or KR plus 100 µM DA. The solutions were equilibrated with oxygen (O2) (10%, 21%, or 95%), and 5% carbon dioxide with the balance being nitrogen. Diaphragm isometric twitch and subtetanic contractions were measured intermittently over 65 minutes (min). The diaphragms were then removed and using a nuclear differential dye uptake method, the percentage of normal, apoptotic and necrotic nuclei were determined using fluorescent microscopy. There were significantly fewer apoptotic nuclei in the DA group diaphragms than the KR only 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 DA's affect on muscle performance. DA decreased diaphragmatic apoptosis perhaps by preventing the activation of intricate apoptotic pathways, stimulating antiapoptotic mechanisms, and/or scavenging free radicals.

Key Words: Diaphragm, Dopamine, Muscle contraction

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