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Improvement of diaphragm and limb muscle isotonic contractile performance by K+ channel blockade.

van Lunteren E, Pollarine J - J Neuroeng Rehabil (2010)

Bottom Line: Most restorative applications involve muscle shortening; however, previous studies on the effects of aminopyridines have involved muscle being held at constant length.The present study tested effects of 3,4-diaminopyridine (DAP) on isotonic contractile performance of diaphragm, extensor digitorum longus (EDL) and soleus muscles from rats.Work and peak power of both diaphragm and EDL were augmented by DAP for considerable periods of time, whereas that of soleus muscle was not affected significantly.

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Affiliation: Division of Pulmonary & Critical Care Medicine, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Case Western Reserve University, Cleveland, OH 44106, USA. exv4@cwru.edu

ABSTRACT
The K+ channel blocking aminopyridines greatly improve skeletal muscle isometric contractile performance during low to intermediate stimulation frequencies, making them potentially useful as inotropic agents for functional neuromuscular stimulation applications. Most restorative applications involve muscle shortening; however, previous studies on the effects of aminopyridines have involved muscle being held at constant length. Isotonic contractions differ substantially from isometric contractions at a cellular level with regards to factors such as cross-bridge formation and energetic requirements. The present study tested effects of 3,4-diaminopyridine (DAP) on isotonic contractile performance of diaphragm, extensor digitorum longus (EDL) and soleus muscles from rats. During contractions elicited during 20 Hz stimulation, DAP improved work over a range of loads for all three muscles. In contrast, peak power was augmented for the diaphragm and EDL but not the soleus. Maintenance of increased work and peak power was tested during repetitive fatigue-inducing stimulation using a single load of 40% and a stimulation frequency of 20 Hz. Work and peak power of both diaphragm and EDL were augmented by DAP for considerable periods of time, whereas that of soleus muscle was not affected significantly. These results demonstrate that DAP greatly improves both work and peak power of the diaphragm and EDL muscle during isotonic contractions, which combined with previous data on isometric contractions indicates that this agent is suitable for enhancing muscle performance during a range of contractile modalities.

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Effects of DAP on fatigue indexes for isotonic work (A) and peak power (B) of diaphragm, extensor digitorum longus (EDL) and soleus during repetitive 20 Hz stimulation at a load of 40%. Asterisks indicate significant increases: ** P ≤ 0.01, * P < 0.05, NS = not significant.
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Figure 5: Effects of DAP on fatigue indexes for isotonic work (A) and peak power (B) of diaphragm, extensor digitorum longus (EDL) and soleus during repetitive 20 Hz stimulation at a load of 40%. Asterisks indicate significant increases: ** P ≤ 0.01, * P < 0.05, NS = not significant.

Mentions: For the diaphragm, there was a brisk initial increase in work near the onset of repetitive stimulation, which was found both in the absence and presence of DAP (Figure 4). However, the magnitude of the early work increase was augmented by DAP. The initial increase was followed by progressive declines in work for both untreated and DAP-treated muscle. Nonetheless, work of DAP-treated muscle was significantly greater than that of untreated muscle (P < 0.001), in particular for the first half of the fatigue testing period. Furthermore, the fatigue index for work was higher in DAP-treated than untreated muscle (indicating a smaller relative drop in work over time with DAP) (Figure 5A). For the EDL, the transient work increase at the beginning of stimulation was both increased and prolonged by DAP, and work was augmented by DAP (P = 0.001) for most of the repetitive stimulation period (Figure 4). However in contrast to the diaphragm, the work fatigue index was similar in the presence and absence of DAP (Figure 5A). Work of the soleus muscle over time was not affected by DAP (P = 0.69) (Figure 4), although the fatigue index was higher in DAP-treated than untreated muscle (Figure 5A).


Improvement of diaphragm and limb muscle isotonic contractile performance by K+ channel blockade.

van Lunteren E, Pollarine J - J Neuroeng Rehabil (2010)

Effects of DAP on fatigue indexes for isotonic work (A) and peak power (B) of diaphragm, extensor digitorum longus (EDL) and soleus during repetitive 20 Hz stimulation at a load of 40%. Asterisks indicate significant increases: ** P ≤ 0.01, * P < 0.05, NS = not significant.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2821379&req=5

Figure 5: Effects of DAP on fatigue indexes for isotonic work (A) and peak power (B) of diaphragm, extensor digitorum longus (EDL) and soleus during repetitive 20 Hz stimulation at a load of 40%. Asterisks indicate significant increases: ** P ≤ 0.01, * P < 0.05, NS = not significant.
Mentions: For the diaphragm, there was a brisk initial increase in work near the onset of repetitive stimulation, which was found both in the absence and presence of DAP (Figure 4). However, the magnitude of the early work increase was augmented by DAP. The initial increase was followed by progressive declines in work for both untreated and DAP-treated muscle. Nonetheless, work of DAP-treated muscle was significantly greater than that of untreated muscle (P < 0.001), in particular for the first half of the fatigue testing period. Furthermore, the fatigue index for work was higher in DAP-treated than untreated muscle (indicating a smaller relative drop in work over time with DAP) (Figure 5A). For the EDL, the transient work increase at the beginning of stimulation was both increased and prolonged by DAP, and work was augmented by DAP (P = 0.001) for most of the repetitive stimulation period (Figure 4). However in contrast to the diaphragm, the work fatigue index was similar in the presence and absence of DAP (Figure 5A). Work of the soleus muscle over time was not affected by DAP (P = 0.69) (Figure 4), although the fatigue index was higher in DAP-treated than untreated muscle (Figure 5A).

Bottom Line: Most restorative applications involve muscle shortening; however, previous studies on the effects of aminopyridines have involved muscle being held at constant length.The present study tested effects of 3,4-diaminopyridine (DAP) on isotonic contractile performance of diaphragm, extensor digitorum longus (EDL) and soleus muscles from rats.Work and peak power of both diaphragm and EDL were augmented by DAP for considerable periods of time, whereas that of soleus muscle was not affected significantly.

View Article: PubMed Central - HTML - PubMed

Affiliation: Division of Pulmonary & Critical Care Medicine, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Case Western Reserve University, Cleveland, OH 44106, USA. exv4@cwru.edu

ABSTRACT
The K+ channel blocking aminopyridines greatly improve skeletal muscle isometric contractile performance during low to intermediate stimulation frequencies, making them potentially useful as inotropic agents for functional neuromuscular stimulation applications. Most restorative applications involve muscle shortening; however, previous studies on the effects of aminopyridines have involved muscle being held at constant length. Isotonic contractions differ substantially from isometric contractions at a cellular level with regards to factors such as cross-bridge formation and energetic requirements. The present study tested effects of 3,4-diaminopyridine (DAP) on isotonic contractile performance of diaphragm, extensor digitorum longus (EDL) and soleus muscles from rats. During contractions elicited during 20 Hz stimulation, DAP improved work over a range of loads for all three muscles. In contrast, peak power was augmented for the diaphragm and EDL but not the soleus. Maintenance of increased work and peak power was tested during repetitive fatigue-inducing stimulation using a single load of 40% and a stimulation frequency of 20 Hz. Work and peak power of both diaphragm and EDL were augmented by DAP for considerable periods of time, whereas that of soleus muscle was not affected significantly. These results demonstrate that DAP greatly improves both work and peak power of the diaphragm and EDL muscle during isotonic contractions, which combined with previous data on isometric contractions indicates that this agent is suitable for enhancing muscle performance during a range of contractile modalities.

Show MeSH
Related in: MedlinePlus