Activation of human quadriceps femoris muscle during dynamic contractions: effects of load on fatigue.

Muscle fatigue is both multifactorial and task dependent. Electrical stimulation may assist individuals with paralysis to perform functional activities [functional electrical stimulation (FES), e.g., standing or walking], but muscle fatigue is a limiting factor. One method of optimizing force is to use stimulation patterns that exploit the catchlike property of skeletal muscle [catchlike-inducing trains (CITs)]. Although nonisometric (dynamic) contractions are important parts of both normal physiological activation of skeletal muscles and FES, no previous studies have attempted to identify the effect that the load being lifted by a muscle has on the fatigue produced. This study examined the effects of load on fatigue during dynamic contractions and the augmentation produced by CITs as a function of load. Knee extension in healthy subjects was electrically elicited against three different loads. The highest load produced the least excursion, work, and average power, but it produced the greatest fatigue. CIT augmentation was greatest at the highest load and increased with fatigue. Because CITs were effective during shortening contractions for a variety of loads, they may be of benefit during FES applications.

Catchlike-inducing train activation of human muscle during isotonic contractions: burst modulation.

Stimulation trains that exploit the catchlike property [catchlike-inducing trains (CITs)] produce greater forces and rates of rise of force than do constant-frequency trains (CFTs) during isometric contractions and isovelocity movements. This study examined the effect of CITs during isotonic contractions in healthy subjects. Knee extension was electrically elicited against a load of 10% of maximum voluntary isometric contraction. The stimulation intensity was set to produce 20% of maximum voluntary isometric contraction. The muscle was tested before and after fatigue with a 6-pulse CFT and 6-pulse CITs that contained an initial doublet, triplet, or quadruplet. For prefatigue responses, the greatest isotonic performance was produced by CITs with initial doublets. When the muscles were fatigued, triplet CITs were best. CITs produce greater excursion, work, peak power, and average power than do CFTs, because CITs produced more rapid rates of rise of force. Faster rates of rise of force enabled the preload on the muscle to be exceeded earlier during the stimulation train.

Preclinical profile of remacemide: a novel anticonvulsant effective against maximal electroshock seizures in mice.

Anticonvulsant tests in mice revealed specific, potent actions of remacemide for protection of mice against maximal electroshock seizures (MES). Comparisons of oral efficacy to reference compounds yielded the following ED50 values (expressed as mg/kg): remacemide = 33, phenytoin = 11, phenobarbital = 20, carbamazepine = 13 and valproate = 631. The duration for protection by remacemide was longer than carbamazepine or valproate, but shorter than phenytoin or phenobarbital. In neural impairment tests (inverted screen or rotorod) to determine the oral toxic dose 50 (TD50) the following therapeutic indices (TD50/ED50) were obtained: (1) inverted screen--remacemide = 17.6, phenytoin = 57.4, phenobarbital = 5.1, carbamazepine = 10.2, and valproate = greater than 3; and (2) rotorod--remacemide = 5.6, phenytoin = 9.6, phenobarbital 4.8, and valproate = 1.9. Remacemide was devoid of sedative actions and possessed a favorable 28.1 margin of safety value (median estimated lethal dose/ED50 for MES). An intermediate potency against either audiogenic- or N-methyl-D-aspartate-induced seizures was exhibited by remacemide. Tolerance to MES was not apparent after 5 days of oral daily dosing of remacemide. Remacemide was inactive in vitro against gamma-aminobutyrate or benzodiazepine receptors and adenosine uptake mechanisms. Therapeutic utility for generalized tonic/clonic seizures is predicted for remacemide.