Improvement of dy/dy dystrophic diaphragm by 3,4-diaminopyridine.
Concerns have been raised that inotropic agents may worsen function of dystrophic muscle due to structural fragility. Studies tested the hypothesis that force increments elicited by potassium (K(+)) channel blockade can be maintained during the course of repetitive stimulation. In vitro twitch force of dy/dy dystrophic mouse diaphragm was significantly lower than normal (796 versus 1271 g/cm(2)). 3,4-Diaminopyridine (DAP) increased twitch force of dystrophic diaphragm by 111 +/- 12% (P <.0001) and increased force at stimulation frequencies of 5-50 Hz by 41-77%. During fatigue-inducing stimulation, force augmentation by DAP was well maintained in dystrophic muscle throughout 25 Hz (P =.0047) and 50 Hz (P =.0059) stimulation. These findings indicate that the K(+) channel blocker DAP augments the force of dystrophic muscle to values close to that of normal muscle over a range of stimulation frequencies. Furthermore, these functional increments can be achieved without causing force to eventually deteriorate below that of untreated dystrophic muscle during fatiguing stimulation. It is possible that DAP may be useful for the clinical management of a variety of disorders causing muscle weakness.[1]References
- Improvement of dy/dy dystrophic diaphragm by 3,4-diaminopyridine. van Lunteren, E., Moyer, M. Muscle Nerve (2002) [Pubmed]
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