Development of an in vitro rat phrenic nerve–diaphragm muscle preparation

PURPOSE: To evaluate in vitro lidocaine and racemic bupivacaine effects in neuromuscular transmission and in neuromuscular blockade produced by rocuronium. METHODS: Rats were distributed in 5 groups (n = 5) in agreement with the studied drugs: lidocaine, racemic bupivacaine, rocuronium, separately (Groups I, II, III); rocuronium in preparations exposed to local anesthetics (Groups IV, V). The concentrations used were: 20 µg/mL, 5 µg/mL and 4 µg/mL, for lidocaine, bupivacaine and rocuronium, respectively. It was evaluated: 1) amplitude of diaphragm muscle response to indirect stimulation, before and 60 minutes after separately addition of lidocaine, racemic bupivacaine and rocuronium and the association of local anesthetics - rocuronium; 2) membrane potentials (MP) and miniature end-plate potentials (MEPP). RESULTS: Lidocaine and bupivacaine separately didn't alter the amplitude of muscle response and MP. In preparations previously exposed to lidocaine and racemic bupivacaine, the rocuronium blockade was significantly larger (90.10 ± 9.15% and 100%, respectively), in relation to the produced by rocuronium separately (73.12 ± 9.89%). Lidocaine caused an increase in the frequency of MEPP, being followed by blockade; racemic bupivacaine produced decrease being followed by blockade. CONCLUSIONS: Local anesthetics potentiated the blockade caused by rocuronium. The alterations of MEPP identify presynaptic action.

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Differential actions of brevetoxin on phrenic nerve and diaphragm muscle in the rat

Toxicon ◽

10.1016/0041-0101(93)90181-h ◽

1993 ◽

Vol 31 (4) ◽

pp. 459-470 ◽

Cited By ~ 6

Author(s):

Sharad S. Deshpande ◽

Michael Adler ◽

Robert E. Sheridan

Keyword(s):

Phrenic Nerve ◽

Diaphragm Muscle

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

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y82-124 ◽

1982 ◽

Vol 60 (7) ◽

pp. 877-884 ◽

Cited By ~ 10

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.

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Neurotoxic Effects of Root Filling Materials on Rat Phrenic Nerve in vitro

Journal of Dental Research ◽

10.1177/00220345820610080501 ◽

1982 ◽

Vol 61 (8) ◽

pp. 1020-1023 ◽

Cited By ~ 56

Author(s):

P. Brodin ◽

A. Røed ◽

H. Aars ◽

D. ørstavik

Keyword(s):

Phrenic Nerve ◽

Filling Materials ◽

Neurotoxic Effects

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Visualization of the diaphragm muscle with ultrasound improves diagnostic accuracy of phrenic nerve conduction studies

Muscle & Nerve ◽

10.1002/mus.24059 ◽

2014 ◽

Vol 49 (5) ◽

pp. 669-675 ◽

Cited By ~ 12

Author(s):

Nicholas E. Johnson ◽

Michael Utz ◽

Erica Patrick ◽

Nicole Rheinwald ◽

Marlene Downs ◽

...

Keyword(s):

Diagnostic Accuracy ◽

Phrenic Nerve ◽

Nerve Conduction ◽

Nerve Conduction Studies ◽

Diaphragm Muscle

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Theophylline minimally alters contractile properties of canine diaphragm in vitro

Journal of Applied Physiology ◽

10.1152/jappl.1990.69.4.1390 ◽

1990 ◽

Vol 69 (4) ◽

pp. 1390-1396 ◽

Cited By ~ 1

Author(s):

E. Derom ◽

S. Janssens ◽

V. De Bock ◽

M. Decramer

Keyword(s):

High Frequency ◽

Force Production ◽

Contractile Properties ◽

Diaphragm Muscle ◽

Muscle Bundle ◽

Time To Peak ◽

Diaphragm In Vitro ◽

Tetanic Tension

We examined the effects of theophylline on contractile properties and high-frequency fatigue of canine diaphragm in vitro. Eighteen diaphragm muscle bundles were obtained from 10 anesthetized dogs and equilibrated in oxygenated Krebs solution to 100, 200, or 300 mg/l theophylline. These bundles were compared with 18 matched control bundles from the contralateral hemidiaphragm. No statistically significant differences in twitch tension, tetanic tension, twitch-to-tetanus ratio, time to peak tension, or half-relaxation time were observed. Concentrations of 300 mg/l theophylline, however, significantly (P less than 0.05) increased force production at 10 Hz by 32%. A similar tendency was present at lower concentrations and exhibited a clear dose-response behavior. High-frequency fatigue was similar in control and theophylline-treated bundles. We conclude that supratherapeutic in vitro concentrations of theophylline do not increase maximal tetanic tension and do not protect against muscle fatigue but potentiate relative force production at low stimulation frequencies. This relatively small effect cannot be explained by poor diffusion of the drug in the muscle bundle, because theophylline concentrations in the muscle bath and in the muscle bundle were virtually identical. Moreover, it remains unclear whether this potentially beneficial effect can be achieved at in vivo attainable serum concentrations.

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Adverse effects of myasthenia gravis on rat phrenic diaphragm contractile performance

Journal of Applied Physiology ◽

10.1152/japplphysiol.01266.2003 ◽

2004 ◽

Vol 97 (3) ◽

pp. 895-901 ◽

Cited By ~ 8

Author(s):

Erik van Lunteren ◽

Michelle Moyer ◽

Henry J. Kaminski

Keyword(s):

Myasthenia Gravis ◽

Muscle Function ◽

Initial Period ◽

Neuromuscular Diseases ◽

Diaphragm Muscle ◽

Twitch Force ◽

Continuous Stimulation ◽

Intermittent Stimulation ◽

Contractile Performance

Myasthenia gravis has variable effects on the respiratory system, ranging from no abnormalities to life-threatening respiratory failure. Studies characterized diaphragm muscle contractile performance in rat autoimmune myasthenia gravis. Rats received monoclonal antibody that recognizes acetylcholine receptor determinants (or inactive antibody); 3 days later, phrenic nerve and diaphragm were studied in vitro. Myasthenic rats segregated into two groups, those with normal vs. impaired limb muscle function when tested in intact animals (“mild” and “severe” myasthenic). Baseline diaphragm twitch force was reduced for both severe ( P < 0.01) and mild ( P < 0.05) myasthenic compared with control animals (twitch force: normal 1,352 ± 140, mild myasthenic 672 ± 99, severe myasthenic 687 ± 74 g/cm2). However, only severe myasthenic diaphragm had impaired diaphragm endurance, based on significantly ( P < 0.05) accelerated rate of peak force decline during the initial period of stimulation (0.02 + 0.02, 0.03 ± 0.01, and 0.09 ± 0.01%/pulse for normal, mild myasthenic, and severe myasthenic, respectively, during continuous stimulation) and intratrain fatigue (up to 30.5 ± 7.4% intratrain force drop in severe myasthenic vs. none in normal and mild myasthenic, P < 0.01). Furthermore, compared with continuous stimulation, intermittent stimulation had a protective effect on force of severe myasthenic diaphragm (force after 2,000 pulses was 31.4 ± 2.0% of initial during intermittent stimulation vs. 13.0 ± 2.1% of initial during continuous stimulation, P < 0.01) but not on normal diaphragm. These data indicate that baseline force and fatigue may be affected to different extents by varying severity of myasthenia gravis and furthermore provide a mechanism by which alterations in breathing pattern may worsen respiratory muscle function in neuromuscular diseases.

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Power fatigue of the rat diaphragm muscle

Journal of Applied Physiology ◽

10.1152/jappl.2000.89.6.2215 ◽

2000 ◽

Vol 89 (6) ◽

pp. 2215-2219 ◽

Cited By ~ 23

Author(s):

Bill T. Ameredes ◽

Wen-Zhi Zhan ◽

Y. S. Prakash ◽

Rene Vandenboom ◽

Gary C. Sieck

Keyword(s):

Diaphragm Muscle ◽

Fiber Types ◽

Rat Diaphragm ◽

Shortening Velocity ◽

Reduction In Force ◽

Novel Technique ◽

Velocity Relationship ◽

Stimulus Train ◽

Force Velocity

We hypothesized that decrements in maximum power output (W˙max) of the rat diaphragm (Dia) muscle with repetitive activation are due to a disproportionate reduction in force (force fatigue) compared with a slowing of shortening velocity (velocity fatigue). Segments of midcostal Dia muscle were mounted in vitro (26°C) and stimulated directly at 75 Hz in 400-ms-duration trains repeated each second (duty cycle = 0.4) for 120 s. A novel technique was used to monitor instantaneous reductions in maximum specific force (Po) andW˙max during fatigue. During each stimulus train, activation was isometric for the initial 360 ms during which Po was measured; the muscle was then allowed to shorten at a constant velocity (30% V max) for the final 40 ms, and W˙max was determined. Compared with initial values, after 120 s of repetitive activation, Po andW˙max decreased by 75 and 73%, respectively. Maximum shortening velocity was measured in two ways: by extrapolation of the force-velocity relationship ( V max) and using the slack test [maximum unloaded shortening velocity ( V o)]. After 120 s of repetitive activation, V max slowed by 44%, whereas V o slowed by 22%. Thus the decrease inW˙max with repetitive activation was dominated by force fatigue, with velocity fatigue playing a secondary role. On the basis of a greater slowing of V max vs. V o, we also conclude that force and power fatigue cannot be attributed simply to the total inactivation of the most fatigable fiber types.

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