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Almitrine and doxapram decrease fatigue and increase subsequent recovery in isolated rat diaphragm

M McGuire1, M F Carey, J J O'Connor

  • 1Department of Human Anatomy and Physiology, University College, Dublin 2, Ireland.

Journal of Applied Physiology (Bethesda, Md. : 1985)
|July 1, 1997
PubMed
Summary
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Almitrine bimesylate and doxapram HCl enhance recovery of rat diaphragm muscle function after fatigue. These respiratory drugs show direct benefits on muscle force and fatigue resistance, particularly almitrine.

Area of Science:

  • Physiology
  • Pharmacology
  • Respiratory Medicine

Background:

  • Almitrine bimesylate and doxapram HCl are known to improve respiratory function by stimulating the phrenic nerve.
  • The direct effects of these drugs on respiratory muscles, like the diaphragm, are less understood, especially concerning muscle fatigue.

Purpose of the Study:

  • To investigate the direct effects of almitrine bimesylate and doxapram HCl on rat diaphragm muscle force production.
  • To determine if these drugs can mitigate or reverse muscle fatigue in different age groups of rats.

Main Methods:

  • In vitro isometric force measurements were performed on rat diaphragm muscle strips.
  • Muscle fatigue was induced using a low-frequency stimulation protocol.
  • The effects of varying concentrations of doxapram HCl and almitrine bimesylate were assessed before and after fatigue, in young (6-14 wk) and aged (50-55 wk) rats.

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Main Results:

  • Doxapram and almitrine, at higher concentrations, increased twitch tension in aged rat diaphragm muscle.
  • Fatigue significantly reduced twitch tension in both age groups, with aged rats showing greater impairment.
  • Both drugs significantly improved the recovery of twitch tension after fatigue, with almitrine demonstrating a more pronounced effect, especially in aged rats.

Conclusions:

  • Almitrine bimesylate and doxapram HCl exert direct positive effects on rat diaphragm muscle contractility and fatigue resistance.
  • These drugs significantly enhance the recovery of muscle function following fatigue, suggesting potential therapeutic applications for respiratory muscle weakness.
  • The observed benefits may involve mechanisms related to intracellular calcium regulation, energy metabolism (ADP/ATP ratios), or antioxidant effects.