Presynaptic Effect of the Aziridinium Ion of Acetylcholine Mustard (Methyl-2-acetoxyethyl-2′-chloroethylamine) on the Phrenic Nerve – Rat Diaphragm Preparation

1975 ◽  
Vol 53 (2) ◽  
pp. 264-272 ◽  
Author(s):  
John G. Clement ◽  
E. Howard Colhoun
Keyword(s):  
Phrenic Nerve ◽  
Neuromuscular Transmission ◽  
Neuromuscular Block ◽  
Neuromuscular Blocking ◽  
Choline Uptake ◽  
Rat Diaphragm ◽  
Neuromuscular Activity ◽  
Aziridinium Ion ◽  
Reported Data ◽  
Frequency Of Stimulation

The rat diaphragm has been used to investigate the neuromuscular blocking action of acetylcholine mustard which yields a potent nicotinic agonist, an aziridinium ion, in aqueous medium. Evidence was obtained that the acetylcholine mustard aziridinium ion impaired neuromuscular activity when the phrenic nerve was stimulated and that the ion did not directly inhibit muscle contraction. Impairment of neuromuscular activity was characterized by a latent period and depended both on the concentration of aziridinium ion and the frequency of stimulation of the phrenic nerve. Elevated concentrations of Ca2+ and choline changed the response of the rat diaphragm to the aziridinium ion, the former increasing the rate of development of neuromuscular block and the latter protecting against neuromuscular block. These results indicated that the aziridinium ion may act either at the site of choline uptake or have an effect on acetylcholine synthesis in the nerve ending and that impairment of neuromuscular transmission in the rat diaphragm involved the availability of acetylcholine. Similar results were obtained with acetylcholine mustard aziridinium ion subjected to alkaline hydrolysis. This substance is thought to be choline mustard aziridinium ion. Although difficult to prove with the rat diaphragm it is possible that acetylcholinesterase of this preparation could hydrolyze acetylcholine mustard aziridinium ion at the neurotransmitter site and the resultant choline mustard aziridinium ion would interfere with the uptake of choline and eventually prevent neuromuscular transmission. This hemicholinium-like hypothesis for the mechanism of action of choline mustard aziridinium ion is compatible with reported data for toxicity of acetylcholine mustard aziridinium ion in the mouse.

The effect of a benzodiazepine, flurazepam, on the response of in vitro skeletal muscle preparations to muscle relaxants: are purines or their receptors involved?

1982 ◽  
Vol 60 (7) ◽  
pp. 877-884 ◽  
Author(s):  
John T. Hamilton ◽  
Peggy A. Stone
Keyword(s):  
Skeletal Muscle ◽  
Phrenic Nerve ◽  
Neuromuscular Blocking ◽  
Muscle Relaxants ◽  
Water Soluble ◽  
Neuromuscular Activity ◽  
Changing Trends ◽  
Low Concentrations ◽  
Partial Blockade

Changing trends in the use of anxiolytic agents and recent reassessment of their neuropharmacological activity has prompted this evaluation of the peripheral neuromuscular activity of the benzodiazepine, flurazepam. In previous reports we have documented peripheral neuromuscular activity of chlordiazepoxide and diazepam on the rat phrenic nerve diaphragm preparation. The water soluble benzodiazepine, flurazepam, has been studied on the rat phrenic nerve diaphragm and frog rectus abdominis in vitro. On the former preparation flurazepam enhanced and then blocked the response to indirect electrical stimulation (0.2 Hz) and readily blocked posttetanic potentiation and prevented the preparation from sustaining a tetanic contracture (30 Hz). On the later preparation, flurazepam blocked in a noncompetitive manner the response of the frog muscle to applied cholinergic agonists. Studies on the rat preparation with the neuromuscular blocking drug succinylcholine have shown an unexpected protection against blockade in preparations pretreated with low concentrations of flurazepam. This was not observed when flurazepam was given prior to d-tubocurarinc. The application of adenosine to rat diaphragms during steady-state partial blockade caused by flurazepam or d-tubocurarine showed an inhibiting action of adenosine which was reversed by theophylline. Pretreatment of rat preparations with dipyridamole significantly enhanced the blocking action of standard concentrations of succinylcholine.These results, along with those in the literature, encourage a reassessment of the action of purines and benzodiazepines on skeletal muscle and encourage a consideration of a possible involvement of purinergic neuromodulation of transmission which is unmasked when the safety factor for transmission is altered by muscle relaxants. The possible clinical significance of protection against succinylcholine by benzodiazepines is noted.

Fatigue of isolated rat diaphragm: role of impaired neuromuscular transmission

1986 ◽  
Vol 61 (3) ◽  
pp. 1077-1083 ◽  
Author(s):  
T. K. Aldrich ◽  
A. Shander ◽  
I. Chaudhry ◽  
H. Nagashima
Keyword(s):  
Neuromuscular Blockade ◽  
Phrenic Nerve ◽  
Neuromuscular Transmission ◽  
Low Frequency ◽  
Rat Diaphragm ◽  
Direct Stimulation ◽  
Low Frequency Stimulation ◽  
Before And After ◽  
Frequency Stimulation ◽  
Isolated Rat

We compared the contributions of impaired neuromuscular transmission (transmission fatigue) and impaired muscle contractility (contractile fatigue) to fatigue of the isolated rat diaphragm. To make this comparison, we measured the differences in active tension elicited by direct muscle stimulation and by indirect (phrenic nerve) stimulation before and after fatigue induced by indirect supramaximal stimulation at varying frequencies and durations. Transmission fatigue was observed after all experimental protocols. Although significant contractile fatigue was not demonstrated after brief periods of low-frequency stimulation (6 min, 15 Hz, 25% duty cycle), it was present after longer or higher frequency stimulation. We repeated the direct stimulation in the presence of neuromuscular blockade with 6 microM d-tubocurarine to demonstrate that a reduced response to stimulation of intramuscular branches of the phrenic nerve during direct stimulation was not responsible for the apparent contractile fatigue. Since we found significant decreases in the response to direct stimulation even after neuromuscular blockade, we could verify the presence of contractile fatigue. We conclude that both contractile and transmission fatigue can occur in the isolated rat diaphragm and that transmission fatigue is a much more important factor after brief periods of fatiguing contractions.

scholarly journals The tof-guard neuromuscular transmission monitor and its use in horses

1999 ◽  
Vol 29 (1) ◽  
pp. 57-62 ◽  
Author(s):  
Juliana Noda Bechara ◽  
Denise Tabacchi Fantoni ◽  
Paulo Sergio de Moraes Barros ◽  
Elton Rodrigues Migliati ◽  
Marcio Augusto Ferreira ◽  
...  
Keyword(s):  
Surgical Procedure ◽  
Neuromuscular Transmission ◽  
Medical Literature ◽  
Neuromuscular Block ◽  
Blocking Agent ◽  
Neuromuscular Blocking ◽  
Neuromuscular Blocking Agent ◽  
Neuromuscular Transmission Monitor ◽  
To Receive ◽  
Neuromuscular Transmission Monitoring

It has been emphasized in the human medical literature, that when using a neuromuscular blocking agent, it is of vital importance the monitoring of the neuromuscular block and that these agents should never be used without it. The purpose of this study was to evaluate the use of the neuromuscular transmission monitor TOF-Guard in horses. Twelve horses were randomly assigned whether to receive pancuronium or atracurium as the neuromuscular blocking agent. All horses were pre-medicated with romifidine, anaesthesia induced with diazepam and ketamine and maintenance with halothane. Abolition of spontaneous ventilation was accomplished by the administration of atracurium or pancuronium. The time from injection of the muscle relaxant agent to the onset of maximum block (T1=0), recovery of T1 to 25% and the recovery of TOF ratio to 0.7 were recorded, as was the time for recovery of T1 from 25 to 75%. It was concluded that it is very important the neuromuscular transmission monitoring during the use of a nondepolarizing neuromuscular blocking agent, since it provides a safer anaesthetic and surgical procedure with the use of adequate dosages and due to the impossibility of a superficialization of the neuromuscular blockade during a surgical procedure. The TOF-Guard showed to be a good option for neuromuscular monitoring in horses.

Effect of hypoxia on neuromuscular transmission in the developing diaphragm

1994 ◽  
Vol 76 (2) ◽  
pp. 708-713 ◽  
Author(s):  
A. R. Bazzy
Keyword(s):  
Nerve Stimulation ◽  
Phrenic Nerve ◽  
Neuromuscular Transmission ◽  
Ringer Solution ◽  
Diaphragm Muscle ◽  
Control Force ◽  
Force Response ◽  
Direct Stimulation ◽  
Frequency Of Stimulation ◽  
Predominant Effect

To study the effects of hypoxia on neuromuscular transmission in the developing diaphragm, phrenic nerve-hemidiaphragm preparations were obtained from newborn (4–9 days) and older (22–30 days) rats. Diaphragms were stimulated directly or indirectly (via the nerve) for 1 s at frequencies of 10–80 Hz. Force generated in response to stimulation was measured during perfusion of oxygenated Ringer solution (control) and Ringer solution bubbled with 95% N2–5% CO2 (hypoxia). After 45 min of hypoxia, the force response of the older diaphragms to direct stimulation had decreased to approximately 50% of control at > or = 40 Hz; however, when stimulation occurred via the nerve at these frequencies only 15–20% of control force was generated. In the newborn diaphragms, the force decrement after similar or longer periods of hypoxia (< or = 90 min) was 30– 40% irrespective of the route or frequency of stimulation. After 15 min of reoxygenation, the force response to both muscle and nerve stimulation recovered completely in the older diaphragms but only partially in the newborn diaphragms (range 77% of control at 50 Hz to 95% of control at 10 Hz). These data suggest that in the newborn diaphragm 1) neuromuscular transmission is more resistant to the effects of hypoxia than the older diaphragm and 2) the predominant effect of hypoxia is peripheral in the diaphragm muscle fibers, whereas in the older diaphragm the effect is before or at the neuromuscular junction.

Developmental changes in neuromuscular transmission in the rat diaphragm

1991 ◽  
Vol 71 (1) ◽  
pp. 280-286 ◽  
Author(s):  
J. D. Feldman ◽  
A. R. Bazzy ◽  
T. R. Cummins ◽  
G. G. Haddad
Keyword(s):  
Phrenic Nerve ◽  
Neuromuscular Transmission ◽  
Peak Force ◽  
Neonatal Rat ◽  
Maximum Force ◽  
Muscle Stimulation ◽  
Rat Diaphragm ◽  
Stimulus Train ◽  
Old Rats

Neuromuscular transmission was studied in diaphragms from rats of three ages, 4–7 days old, 11–12 days old, and adults with the use of an in vitro phrenic nerve-hemidiaphragm preparation. Each hemidiaphragm was stimulated via either muscle or nerve with 1-s stimulus trains at frequencies from 10 to 100 Hz. The patterns of force development obtained in response to the two routes of stimulation were compared for each group. Diaphragms from adults developed maximum force in response to stimulation of approximately 40 Hz with no significant decrease in force at higher frequencies. Within each stimulus train, once peak force was achieved, it was maintained for the remainder of the stimulus and responses to nerve and muscle stimulation were almost identical. In contrast, diaphragms from 4- to 7-day-old rats developed maximum force at approximately 20 Hz; stimulation at greater than or equal to 60 Hz induced significantly less peak force. This decrease in peak force at higher frequencies was significantly larger for nerve than for muscle stimulation. In addition, during each nerve stimulus train diaphragms from 4- to 7-day-old rats were unable to maintain peak force, which decreased at frequencies greater than 20 Hz. The decrease in force reached approximately 50% of peak at stimulation frequencies greater than or equal to 60 Hz. Diaphragms from 11- to 12-day-old rats showed intermediate responses. Based on the responses to phrenic nerve stimulation, we conclude that the neonatal rat diaphragm shows marked neuromuscular transmission failure that is not seen in the adult.(ABSTRACT TRUNCATED AT 250 WORDS)

Characterization of the neuromuscular block produced by clindamycin and lincomycin

1976 ◽  
Vol 54 (6) ◽  
pp. 937-944 ◽  
Author(s):  
J. M. Wright ◽  
B. Collier
Keyword(s):  
Neuromuscular Block ◽  
Active Form ◽  
Neuromuscular Blocking ◽  
Rat Diaphragm ◽  
Depressant Effect ◽  
Clinical Toxicity ◽  
Local Anaesthetic Effect ◽  
Nerve Muscle ◽  
Anaesthetic Effect

The site of neuromuscular blockade induced by clindamycin and lincomycin was studied on isolated nerve and nerve–muscle preparations. Clindamycin (3.6 × 10−3 M) but not lincomycin (up to 1.5 × 10−2 M) had a local anaesthetic effect on a frog desheathed nerve preparation. Clindamycin (8 × 10−4 M) and lincomycin (4 × 10−3 M) depressed the response of the rat diaphragm to nerve stimulation and to direct muscle stimulation in parallel. This indicated that the predominant neuromuscular blocking effect of these antibiotics was due to an effect on the muscle. Clindamycin was fivefold more potent than lincomycin in this effect, and the unionized form of both drugs was the active form. Lincomycin (4 × 10−3 M) but not clindamycin (8 × 10−4 M) also had some depressant effect on nerve–muscle transmission as indicated by the interaction of the effects of the antibiotics and d-tubocurarine. The significance of these findings is discussed in relation to the acute clinical toxicity of these antibiotics.

scholarly journals Influence of stimulus frequency on blockade induced by pancuronium and rocuronium: study on rats phrenic nerve-diaphragm preparation

2007 ◽  
Vol 22 (6) ◽  
pp. 446-450 ◽  
Author(s):  
Angélica de Fátima de Assunção Braga ◽  
Derli Conceição Munoz ◽  
Franklin Sarmento da Silva Braga ◽  
Daniele Ribeiro de Araujo ◽  
Glória Maria Braga Potério ◽  
...  
Keyword(s):  
Neuromuscular Blockade ◽  
Phrenic Nerve ◽  
Stimulus Frequency ◽  
Neuromuscular Blocker ◽  
Rat Diaphragm ◽  
Frequency Stimulation ◽  
Time Periods ◽  
Frequency Of Stimulation ◽  
Stimulation Of

PURPOSE: To evaluate the influence of two stimulation frequencies on the installation of neuromuscular blockade produced by pancuronium and rocuronium on the rat diaphragm. METHODS: Diaphragms were submitted to an indirect frequency stimulation of 0.1 and 1Hz (Groups I and II, respectively). Subgroups were formed (n=5) according to the neuromuscular blocker employed (pancuronium-2µg/ml and rocuronium-4µg/ml). The twitch height depression was evaluated at 5, 15 and 30 minutes after adding the neuromuscular blocker. RESULTS: The decrease in twitch height was greater (p<0.01) with a frequency of 1Hz at all time periods studied both in preparations that are blocked with pancuronium and in those that are blocked with rocuronium. CONCLUSION: The frequency of stimulation interferes significantly with the installation of neuromuscular blockade produced by pancuronium and rocuronium, since the reduction in amplitude of the rat diaphragm response was greater for 1Hz frequencies, at all periods studied.

scholarly journals Neuromuscular block induced by bothrops moojeni snake venom and the effect of Jatropha ellíptica starch

2020 ◽  
Vol 12 (1) ◽  
pp. 651-662
Author(s):  
Sára Cósta Ferreira Rodrigues ◽  
Edson Hideaki Yoshida ◽  
Yoko Oshima Franco ◽  
Marcio Galdino dos Santos ◽  
Carla Simone Seibert
Keyword(s):  
Phrenic Nerve ◽  
Neuromuscular Block ◽  
Protein Profile ◽  
Activity Time ◽  
Nerve Activity ◽  
Neuromuscular Activity ◽  
Granulometric Analysis ◽  
Sds Page ◽  
Before And After ◽  
Bothrops Moojeni

This research evaluated the effect of Bothrops moojeni venom on neuromuscular activity and verified the anti-phallic potential of the J. elliptica starch in this model. The venom was obtained from snakes collected in the state of Tocantins, the protein profile evaluated in electrophoresis (SDS-PAGE), and the activity on the phrenic-diaphragm nerve of mice determined in 50 µg/mL of venom. The JeP, obtained by hand, was sieved in a sieve for granulometric analysis and concentrations of 100 and 1000 µg/mL were tested to verify its anti-phallic potential on the action of the poison. The following models were used: pre-venom - addition of venom and after 15 min addition of JeP; post-poison - addition of JeP and after 15 min the addition of poison; and pre-incubation - for 30 min, of poison with JeP or commercial antivenom. The poison had proteins from 10 to 60 kDa, which induced 50% of neuromuscular activity block in 71.5 ± 8.9 min (T50). The pre-venom and post-venom models with JeP 100 µg/mL prolonged phrenic nerve activity time (100.9 ± 7.6 min and 97 ± 6.1 min, respectively). The results obtained for 1000 µg/mL and in the model of pre-incubation of the venom with JeP 100 (78.2 ± 9.2); 1000 µg/mL (86.5 ± 8.9) and with commercial botropic antivenom (80.2 ± 14.1), did not interfere with the activity of the venom on the phrenic nerve. Bothrops moojeni venom induces neuromuscular block and the lower concentration of the starch caused a protective effect on the junction, before and after the administration of the venom.

Evaluation of Recovery From Nondepolarizing Neuromuscular Block, Using a Digital Neuromuscular Transmission Analyzer

1973 ◽  
Vol 52 (5) ◽  
pp. 740???744 ◽  
Author(s):  
HASSAN H. ALI ◽  
RICHARD J. KITZ
Keyword(s):  
Neuromuscular Transmission ◽  
Neuromuscular Block
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