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Biomedical subjects

W F Riker

Publications and source records attributed to W F Riker.

At least 19 recordsLinked to original sources
PubMed1992

Neuromuscular pharmacology in rat neonates: development of responsiveness to prototypic blocking and reversal drugs.

The neonatal pharmacology of neuromuscular drugs was studied in vivo in newborn rats and in vitro in neonatal phrenic nerve-hemidiaphragm preparations. Drugs used to probe neuromuscular development in rat neonates were physostigmine, edrophonium, neostigmine, 4-aminopyridine, d-tubocurarine (dTc), and succinylcholine. The prejunctional actions of these drugs were monitored in relation to neonatal age by the appearance of stimulus-evoked repetitive discharge initiated by motor nerve endings and the occurrence and magnitude of the resulting enhancement of twitch tension. The occurrence and incidence of drug-induced fasciculations also served to track the development of functional motor nerve endings. Each of these prejunctional actions was inoperative until the third neonatal week, indicative of incomplete motor nerve development. In contrast, 4-aminopyridine, a nonanticholinesterase, evoked these prejunctional actions in 1-wk-old rat neonates. Neostigmine and edrophonium antagonized dTc as early as the first week; presumably, postsynaptic maturation had reached a functional level. 4-Aminopyridine also antagonized dTc at week 1. Rat neonates showed resistance to dTc blockade when tested by neonatal phrenic nerve-hemidiaphragm preparations in vitro. Relationships between age and 85%-95% transmission block declined to the adult level by week 5. This result indicates that in rat neonates, pharmacodynamic rather than pharmacokinetic mechanisms predominate in the development of responsiveness to dTc.

4-Aminopyridine↗
PubMed1990

The interactions of ouabain with post-tetanic and facilitatory drug potentiations at cat soleus neuromuscular junctions in vivo.

Cat soleus motor nerve terminals, after high frequency conditioning, generate a post-tetanic repetition (PTR) which leads to a post-tetanic (PTP) of the muscle response. This property enables quantitative assessment of enhancement or depression of this nerve terminal excitability in vivo. The present study focuses on ionic mechanisms underlying the PTRs produced in this neuromuscular system either by high frequency stimulation or edrophonium. Ouabain was used as a specific probe for inhibition of Na(+)-K+ ATPase and its known consequences on Na+ and Ca2+ translocation. Ouabain pretreatment doubled the duration over which single stimuli, following either high frequency or edrophonium conditioning produced PTR. Ouabain in the doses used had no effect per se but as a function of dose augmented the frequency dependent responses. This pointed to Na+ loading of nerve terminals via high frequency stimulation plus ouabain inhibition of Na(+)-K+ ATPase. Ouabain potentiation of PTR responses evidently depends on exchange of intra-terminal sodium for external calcium. Thus, calcium entry blockers, Mn2+, and Co2+ suppressed or abolished the potentiations both before and after ouabain. Diphenylhydantoin, a Na+ and Ca2+ blocker, acted similarly. The effects of stimulation frequency, ouabain and the sequence of events leading to PTR in the soleus neuromuscular system appeared in general no different from those derived from the many in vitro microphysiologic studies of this phenomenon. Thus, EPPs were augmented and prolonged. It was concluded that intracellular Ca2+ is critical for regulating the stability of systems in which repetitive firing is both a normal and abnormal function.

Animals↗
PubMed1988

Motor nerve ending disorder in myasthenia gravis.

Mild myasthenia gravis patients were compared with normals with respect to the capacity of their motor nerve endings (MNEs) to generate a neostigmine-induced postactivation repetition (PAR). Dose-response analyses of PAR recorded from muscle electrically and by contractile measurement disclose a loss of this pharmacologic responsiveness in myasthenia. Since mild myasthenics transmitted nerve impulse trains of 20 to 200 Hz, as did normals, it was evident that PAR is transmitted insofar as it can be generated by MNEs. The dose-response analyses support this. These data indicate an MNE disorder in the disease.

Action Potentials↗
PubMed1986

Succinylcholine: mechanism of fasciculations and their prevention by d-tubocurarine or diphenylhydantoin.

Administration of d-tubocurarine (dTC) or diphenylhydantoin (DPH) was evaluated as a pretreatment to prevent succinylcholine (Sch) evoked fasciculations. Experiments were designed to determine the nature of the drug-drug interactions, sites of interaction, and site of fasciculation suppression. Sch is known to evoke repetitive discharge generation by motor nerve terminals (MNTs). Transmission of these prejunctional discharges causes fasciculations. A cat soleus neuromuscular preparation in situ, which enables recording of nerve action potentials initiated by MNTs, their transmitted muscle action potentials, and the resultant contractile responses, was used to explore Sch effects before and after iv pretreatment with dTC or DPH. dTC is known to act prejunctionally to suppress repetitive discharges initiated by facilitatory drugs and tetanic conditioning of MNTs. Accordingly, pretreatment with dTC 50 micrograms X kg-1 suppressed the Sch-induced MNT repetitive discharging and correspondingly suppressed generalized fasciculations without affecting twitch. This dTC dose, however, also reduced Sch blocking potency by 33%, slowed its rate, and shortened block duration. These latter effects represent competitive postjunctional antagonism. DPH is also known to suppress MNT repetitive discharging. Correspondingly, Sch-induced repetitive firing and ensuing fasciculations were suppressed by DPH (30 mg X kg-1) without affecting twitch. Unlike dTC, this DPH dose increased Sch blocking potency by 50%, increased the initial rate of block, and did not alter block duration. These DPH effects were dose-dependent and within the anticonvulsant range for cats. Therefore, patients with anticonvulsant levels of DPH may not require pretreatment before Sch.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

d-Tubocurarine sensitivities of a fast and a slow neuromuscular system of the rat.

Fast and slow neuromuscular systems in the rat were compared with respect to their sensitivity to d-tubocurarine (dTC). The fast tibialis anterior was more sensitive than the slow soleus to dTC-induced block of contractile tension when stimulated at either 0.2 or 1.0 Hz. These results in the rat contrast those made by others in the cat. Thus, relative drug sensitivities are not simply related to neuromuscular type.

Animals↗
PubMed1985

Prolongation of procaine's and procainamide's actions by binding to acryloyl polymers.

Procaine and procainamide were covalently bound to acryloyl monomers and polymers. The dose-response and time-action parameters of the cardiac antiarrhythmic protection afforded by the prototype drugs and their acryloyl derivatives against chloroform-hypoxia-induced cardiac arrhythmias in unanesthetized mice and epinephrine-induced arrhythmias in alpha-chloralose anesthetized cats were determined. Similarly, the pharmacological parameters which characterized their acute toxic responses in unanesthetized male albino mice were also determined. The similar pharmacological spectra of their activity and the parallelism of their lethal dose-response curves indicate that the active constituents of the polymer derivatives are the local anesthetic moieties. Compared to the prototype drugs, the polymer derivatives were more potent on a molar basis and their pharmacological effects were prolonged. The increased potency and duration of action reinforce the idea that the local anesthetic moieties are pharmacologically active while still bound to the polymer backbones.

Acrylic Resins↗
PubMed1985

Pharmacologic excitability of rat motor nerve endings: the effect of adrenalectomy on neostigmine-induced fasciculations.

Neostigmine-induced muscle fasciculations, quantitated as fasciculatory muscle action potentials, served as an indirect in vivo indicator of motor nerve ending (MNE) excitability. By this method, MNE excitability was depressed in adrenalectomized rats compared to matched intact controls. Daily or continuous administration of the mineralocorticoids aldosterone or desoxycorticosterone acetate restored MNE excitability toward normal; corticosterone, the endogenous corticosteroid having both mineralo- and glucocorticoid activity, was variably effective. There was a strong negative correlation (r = -0.95) between log plasma [K+]and the fasciculatory response to neostigmine. Dietary restriction of K in adrenalectomized rats lowered plasma [K+]to near normal and significantly increased MNE excitability. This effect of adrenalectomy on MNE excitability was further demonstrated by recording directly the neostigmine-induced repetitive neural discharges responsible for the muscle fasciculations. In adrenalectomized animals, neostigmine-induced neural discharges were reduced in intensity; restoration of neostigmine responsiveness was attained by lowering plasma [K+]through dietary restriction. Stimulus strength-duration relationships for both ventral and dorsal roots disclosed deficits in axonal excitability after adrenalectomy. These returned toward normal when plasma [K+]was lowered by K withdrawal from the diet. From these studies, it is concluded that 1) in adrenalectomized rats, peripheral nerve excitability, including the unmyelinated endings of motor nerve, is depressed; 2) mineralocorticoids play a significant role in restoring MNE excitability in these animals; 3) mineralocorticoid-induced changes in MNE excitability relate to the lowering of an elevated plasma [K+].

Action Potentials↗
PubMed1983

Beneficial action of glucocorticoid treatment on neuromuscular transmission during early motor nerve degeneration.

The effects of a short-term, high-dose glucocorticoid pretreatment regimen (triamcinolone diacetate, 8 mg/kg i.m. daily for 7 days) were examined on neuromuscular transmission deficits observed in the in vivo cat soleus nerve-muscle preparation at 48 hr after soleus nerve transection. The pretreated preparations had 20% more functional motor nerve terminals than the untreated. This was evidenced by a significantly (P less than 0.01) lesser difference in the indirectly evoked isometric contractile tensions between the denervated muscle and the contralateral intact preparation as a result of prior glucocorticoid treatment. The glucocorticoid pretreatment also significantly improved the capacity of the trophically deprived soleus motor nerve terminals to maintain transmission during high-frequency activation (100 to 400 Hz for 10 s). Moreover, triamcinolone treatment before nerve transection completely prevented the development of an increased sensitivity to d-tubocurarine neuromuscular block in untreated, 48-h nerve-transected preparations. These results demonstrate an ability of an intensive high-dose glucocorticoid treatment to sustain single and repetitive neuromuscular transmission during early anterograde nerve degeneration.

Animals↗
PubMed1982

A morphological study of the effect of glucocorticoid treatment on delayed organophosphorus neuropathy.

The delayed neuropathy caused by the organophosphate diisopropylfluorophosphate (DFP) can be minimized by a high dose glucocorticoid regimen started after exposure to DFP. In cats 21 days after an intraarterial injection (2 mg/kg) of DFP, morphologic alterations of neuromuscular junctions and myelinated intramuscular axons are evident. These alterations include the presence of extensive lamellar whorls in nerve axons and terminals, the disruption and retraction of nerve terminals from the synaptic cleft and a widening of secondary junctional folds with coincident dispersion of the basal lamina. The pathologic changes while more intense in the DFP-treated leg are also evident in the contralateral leg. Only 2% of motor nerve terminals from the soleus of DFP-treated legs were rated as normal in morphologic evaluations. In contrast 90% were rated normal in cats exposed to DFP and subsequently treated with one dose of methyl prednisolone (90 mg/kg, i.v.) and 7 doses (8 mg/kg, i.m.) of triamcinolone over a 20 day period. The mechanism whereby glucocorticoid therapy exerted this effect during the time interval studied remains unresolved. However, this observation may be important in the further definition of both the normal and diseased state.

Animals↗
PubMed1979

Myokymia and impaired muscular relaxation with continuous motor unit activity.

We have studied two cases of the syndrome of myokymia and impaired muscular relaxation with continuous motor unit activity. Both patients complained of muscle twitching, weakness, stiffness, and hyperhydrosis during their illness. Myokymia was present over the entire body in both. On repetitive testing of muscle strength each patient showed initial fatigue followed by increasing strength as he continued his efforts. Both patinets improved on phenytoin therapy at high blood levels. Nerve conduction velocities were decreased. Electromyograms showed continuous electrical activity at rest which persisted during sleep and spinal anaesthesia but was diminished by curare. Intravital staining with methylene blue in one case demonstrated sprouting and beading of motor nerve terminals with multiple innervation of muscle fibres. The neurophysiological and pathological findings in these two cases indicate an abnormality of peripheral nerve in this disorder.

Adult↗
PubMed1978

The neuropathology of DFP at cat soleus neuromuscular junction.

The fine structure of the cat soleus neuromuscular junction was studied following a single intra-arterial injection of di-isopropylfluorophosphate (DFP) into the right femoral artery. DFP induced separate subacute and delayed morphologic changes in soleus non-myelinated motor nerve terminals. Three days after DFP administration motor nerve terminals were reduced in number. Subacute DFP damage was also noted in the subneural apparatus and in the immediate subjacent muscle. Both pre- and post-junctional subacute changes were resolved two weeks post-DFP. One week following this initial regeneration, soleus motor nerve terminals underwent a delayed transient degeneration, followed by reinnervation of damaged endplates 6--8 weeks following DFP. Quantitative analysis of methylene blue-stained intramuscular nerves indicated that both subacutely and chronically denervated soleus muscle fibres were reinnervated by regeneration of the original motor axon. Reinnervation by means of collateral sprouting was insignificant. This mechanism of reinnervation and the rapidity with which it occurred suggests that both subacute and delayed soleus motor nerve damage is initiated from local actions of DFP on the non-myelinated terminal. The subacute reaction probably results from a direct cytotoxic action of DFP at pre- and post-junctional sites. The delayed nerve terminal degeneration may also stem from an acute effect not immediately detrimental to nerve function.

Animals↗
PubMed1977

Effects of a single methylprednisolone dose on a facilitatory response of mammalian motor nerve.

Long-term glucocorticoid dosing directly enhances a facilitatory function of cat soleus motor nerve terminals. Posttetanic potentiation (PTP) of soleus contraction is a manifestation of this prejunctional facilitation. The present study demonstrates that the same enhancement of facilitation is produced with a single large intravenous dose methylprednisolone. The single dosing method, however, showed an initial suppression of facilitation that neared recovery in four hours. Thereafter, the characteristic augmentation of prejunctional facilitation emerged, peaking in 24 hours. Return to control required four days. Knowledge of this time course enabled centrally disconnected motor nerve endings to be identified as the site of both phases of the steroid action. Since the neuromuscular facilitation studied is equivalent to that triggered by neostigmine-like drugs, the results infer that the antimyasthenic effect of glucocorticoids may involve a direct action on motor nerve endings.

Animals↗