Effect of Duration of Lower Motor Neuron Injury on Mivacurium-induced Muscluar Relaxation in Rabbits / 대한마취과학회지

BACKGROUND: The purpose of this study was to investigate whether the effects of mivacurium on muscular relaxation were similar by the duration of more than 2 weeks after the injury of lower motor neurons in rabbits. METHODS: The animals were divided into five groups. The control group was without lower motor neuron injury. In the experimental groups, the lower motor neuron injury was made by denervating with 75 - 80% lesion on the common peroneal nerve to the right anterior tibialis muscle. The experimental groups were subdivided as 1, 2, 3 and 4 week groups (referred to ad the 1 wk, 2, 3 and 4 wks group) according to the durations of the denervation of common peroneal nerve, respectively. The dose-response relationship of mivacurium on the muscle twitches induced by TOF (train of four) stimulation (supramaximal stimulus of 0.2 ms duration, square-wave pulses, 2 Hz rate, repeated every 10 seconds) was studied by calculating ED50 and ED95 in the anterior tibialis muscles and compared between all groups. After recording the muscle twitches, microscopic findings were observed. RESULTS: The effective dose for 95% twitch depression (ED95) of mivacurium at 1week after denervation was significantly higher than that of the control group (P <0.05), but the ED95 of 2, 3 and 4wks groups were not significantly different from that of the control group. However, the ED95 of 3 and 4wks group were inclined to be lower than that of the control and significantly lower than 1wk group (P < 0.05). There was no significant difference in the effective dose for 50% twitch depression (ED50) of mivacurium in all groups. The size of the anterior tibialis muscle was significantly decreased at 4weeks after the lower motor neuron injury (P <0.05), but the number of its sarcoplasmic nuclei was increased, according to the duration after the denervation. CONCLUSIONS: Our results therefore suggest that neuromuscular response of denervated anterior tibial muscle was resistant to intravenous mivacurium in early periods of 1 or 2 weeks but sensitive 4 weeks after the lower motor neuron injury.

Neuromuscular Blocking and Vagolytic Effects of Atracurium, Cisatracurium, and Mivacurium in the Anesthetized Cat / 대한마취과학회지

BACKGROUND: Atracurium is a benzylisoquinolium nondepolarizing neuromuscular blocking drug. It releases histamine upon the rapid administration of more than 2 x ED95. Cisatracurium is about three to four times more potent than atracurium, less likely to release histamine, and has weaker cardiovascular or autonomic effects. Mivacurium releases histamine to about the same degree as atracurium at the same dose. This study was undertaken to reevaluate the experimental model for the evaluation of effects on the autonomic nervous system, and to determine the neuromuscular blocking profiles and the vagolytic effects of atracurium, cisatracurium and mivacurium in cats. METHODS: Cats, either sex, anesthetized with pentobarbital, were used. Neuromuscular blocking effects were assessed using the effects on the anterior tibialis muscle twitch evoked with supramaximal stimuli (0.2 ms-duration, 0.1 Hz). Inhibition of the parasympathetic nervous system was assessed in response to bradycardia to vagal nerve stimulation with ten-second trains of square-waves (0.5 ms-duration, 20 Hz). The dose-response curves for both neuromuscular blocking and vagolytic actions were determined for each animal. The dose-response curves were constructed in cumulative fashion. The response for vagal stimuli was measured two minute after each dosing. Vagal ID50 (The doses that produced 50% inhibition of the response to vagus nerve stimulation) were determined. RESULTS: NMB ED95 and NMB ED50, respectively, were 102.0 +/- 28.3 and 143.7 +/- 40.5 microgram/kg for atracurium, 81.4 +/- 13.3 and 110.7 +/- 18.8 microgram/kg for cisatracurium, and 56.8 +/- 17.4 and 74.2 +/- 25.0 microgram/kg for mivacurium. Vagal ID50 was 2,654 +/- 1,651 microgram/kg for atracurium, 655 +/- 389 microgram/kg for cisatracurium, and 606 +/- 182 microgram/kg for mivacurium. The vagal ID50/NMB ED95 and vagal ID50/NMB ED50 were 18.5 and 26.0 for atracurium, 5.9 and 8.1 for cisatracurium, and 8.2 and 10.7 for mivacurium. CONCLUSIONS: Atracurium has a wider margin of safety only for vagal stimulation as compared with cisatracurium and mivacurium. However, we couldn't exclude that either sympathetic stimulation or histamine release might contribute to heart rate.

The Effects of Vecuronium and Pancuronium on the Tension of the Isolated Rat Tracheal Smooth Muscle / 대한마취과학회지

BACKGROUND: Non-depolarizing muscle relaxants have their muscle relaxing effect by competing with acetylcholine (ACh) at the nicotinic receptor level. What are the effects of such muscle relaxants on the tracheal smooth muscle? This present study was set up to address the question as to how vecuronium and pancuronium influence the tracheal smooth muscle. METHODS: Sixty male Sprague-Dawley rat tracheal smooth muscles were isolated at optimal length for isometric force. The preparations were set up in an organ bath containing Tyrode's solution. And isometric force displacement transducer and physiograph were used to record the change in force. After the equilibration period the preparations were contracted with ACh 10(-5) M and carbachol 3x10(-7)M seperately. The preparations were washed with fresh tyrode's solution and allowed to return passively to resting tone. Then the cumulartive effect of ACh (from 3 10(-7) M through 10(-5) M) and carbachol (CCh, from 10(-8) M through 3 10(-6) M) were produced before and after pretreating the preparation with vecuronium (10(-5) M and 10(-6) M) and pancuronium (10(-5) M and 10(-6) M) respectively. Also, we studied the changes of contraction produced by neostigmine before and after pretreatment with vecuronium (10(-5) M and 3 10(-5) M) and pancuronium (3 10(-6) M and 3 10(-5) M). RESULTS: Vecuronium shifted the ACh dose-response curve of the tracheal contraction to the left (p0.05). CONCLUSIONS: Vecuronium inhibits the ACh hydrolyzing enzyme, especially acetylcholinesterase. Therefore it potentiates ACh contraction in the tracheal smooth muscle, but not the CCh contraction, while pancuronium has a different effect in comparison with vecuronium. That is, at a low concentration it reveals an antagonistic effect on the muscarinic M2 receptor and at a higher concentration it has an antagonistic effect on the muscarinic M3 receptor in the tracheal smooth muscle.

Effect of Sevoflurane and Isoflurane on Hypoxic Pulmonary Vasoconstriction in the Isolated Rabbit Lung / 대한마취과학회지

BACKGROUND: In vitro and in vivo studies have shown that inhalation anesthetics inhibit hypoxic pulmonary vasoconstriction (HPV). The aim of this study was to investigate the effect of isoflurane and sevoflurane on HPV in the isolated rabbit lungs. METHODS: Isolated constant-flow perfused lungs from New Zealand white rabbit were randomly allocated to treatment with either isoflurane (n=8) or sevoflurane (n=8). HPV, defined as an increase in pulmonary arterial pressure at constant flow, was elicited by decreasing inspiratory oxygen concentration from 95% to 3% for 5 min. This effect was determined without and with increasing concentration of anesthetics (at 0.5, 1.0, and 2.0 MAC of isoflurane, and at 0.6, 0.9, and 1.2 MAC of sevoflurane). The HPV response in the presence of anesthetics was expressed as a percentage of the pressor response in the absence of anesthetics and dose-response relationship were calculated using the nonlinear least-squares method. RESULTS: The percent hypoxic pressor response (%deltaP) of isoflurane were 100%, 78.4%, 45.1%, and 19.6% at 0, 0.5, 1.0, and 2.0 MAC, respectively. The %deltaP of sevoflurane were 100%, 66.6%, 40.0%, and 22.2% at 0, 0.6, 0.9, and 1.2 MAC, respectively. Values (mean+/-SD) for the half-inhibition values (ED50) were 0.90+/-0.14 and 0.81+/-0.15 MAC, and for the slopes were 1.97+/-0.52 and 1.84+/-0.59 for isoflurane and sevoflurane, respectively. There were no statistical difference between the values for ED50 or between the values for slope. CONCLUSIONS: We conclude that sevoflurane and isoflurane inhibit the HPV reponse in a dose-related manner with same potency and slope.