Association between levobupivacaine and pancuronium. Interference in neuromuscular transmission and blockade in rats

ABSTRACT PURPOSE: To evaluate the effects of levobupivacaine on neuromuscular transmission and neuromuscular blockade produced by pancuronium in vitro. METHODS: Thirty rats were distributed into groups (n = 5) according to the drug used alone or in combination: Group I - levobupivacaine (5 µg.mL-1); Group II - pancuronium (2 µg.mL-1); Group III - pancuronium (2 µg.mL-1) + levobupivacaine (5µg.mL-1). The following parameters were evaluated: 1) amplitude of diaphragmatic response to indirect stimulation, before and 60 minutes after the addition of levobupivacaine and pancuronium alone, and after the addition of levobupivacaine combined with pancuronium; 2) membrane potentials (MP) and miniature endplate potentials (MEPP). RESULTS: Levobupivacaine alone did not alter the amplitude of muscle response and MP. In preparations previoulsy exposed to levobupivacaine, the block with pancuronium was significantly denser (90.2 ± 15.2%), showing a significant difference (p=0.031) in comparison to the block produced by pancuronium alone (48.9% ± 9.8%). There was a decrease in the frequency and amplitude of MEPPs. CONCLUSION: Levobupivacaine potentiated the neuromuscular blockade produced by pancuronium, confirming a presynaptic action by a decrease in miniature endplate potentials.

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

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.

OBJETIVO: Avaliar a influência de duas freqüências de estimulação na instalação do bloqueio neuromuscular induzido por pancurônio e rocurônio em diafragma de ratos. MÉTODOS: Os diafragmas foram submetidos a uma freqüência de estimulação indireta de 0.1 e 1Hz (Grupos I e II, respectivamente). Os animais foram divididos em subgrupos (n=5) de acordo com o bloqueador neuromuscular a ser utilizado (pancurônio-2µg/mL e rocurônio-4µg/mL). A amplitude das respostas musculares foi avaliada 5, 15 e 30 minutos após a adição do bloqueador neuromuscular à preparação. RESULTS: A redução na intensidade da contração foi maior (p<0.01) com a freqüência de 1Hz em todos os tempos avaliados para as preparações contendo pancurônio e rocurônio CONCLUSION: A freqüência de estímulo interfere significativamente na instalação do bloquio neuromuscular produzido por pancurônio e rocurônio, uma vez que a redução na amplitude da resposta do diafragma foi maior para a freqüência de 1Hz em todos os períodos estudados.

Effects of calcium, strontium, and barium on isolated phrenic nerve-diaphragm preparation of rat and their interactions with diltiazem and nifedipine.

Calcium (Ca2+), strontium (Sr2+), and barium (Ba2+) are expected to exert similar chemical and pharmacological effects. The effects of barium, strontium and calcium were studied on the contractions of rat phrenic nerve-diaphragm preparations, following electrical stimulation and their interactions with nifedipine (nif) and diltiazem (DZM) were also studied. Low doses of strontium chloride (SrCl2), barium chloride (BaCl2) and calcium chloride (CaCl2) were able to increase the force of contraction of the rat diaphragm when actively stimulated. Diltiazem inhibited the stimulant effects of Sr2+, Ba2+, and Ca2+. On the other hand, nifedipine blocked the effects of Sr2+ and Ca2+ but potentiated the effects of Ba2+. Strontium, barium, and calcium restored the contractility of the muscle following electrical stimulation when the tissue was in biological fluid absolutely depleted of calcium. These findings suggest that Sr2+ and Ba2+ may be able to substitute Ca2+ in the rat diaphragm for its contractions and nifedipine and diltiazem may follow different mechanisms of actions or channels in their blocking effects.

Effect of shenmai injection on L-type calcium current of diaphragmatic muscle in rats / 华中科技大学学报（医学）（英德文版）

In this study, whole cell patch clamp recording technique was employed to investigate the effect of Shenmai Injection (SMI) on L-type calcium current of diaphragmatic muscle in rats. The result showed that when the diaphragmatic muscle cell was held at -80 mV and depolarized to +60 mV, 10 microl/ml, 50 microl/ml and 100 microl/ml SMI enhanced the inner peak L-type calcium current from -(6.8 +/- 0.7) pA/pF (n=7) to -(7.3 +/- 0.8) pA/pF (P>0.05, n=7), -(8.6 +/- 1.0) pA/pF (P<0.05, n=7) and -(9.4 +/- 1.2) pA/pF (P<0.05, n=7), respectively, The rates of L-type calcium current were increased by (7.34 +/- 2.37)%, (25.72 +/- 5.94)%, and (38.16 +/- 7.33)%, respectively. However, it had no significant effect on maximal activation potential and reversal potential. Our results suggested that SMI could activate the calcium channel of the diaphragmatic fibers of the rats, increase the influx of Ca2+, and enhance the contractility of diaphragmatic muscles.

Effects of L-arginine on the diaphragm muscle twitches elicited at different frequencies of nerve stimulation

In rats, the nitric oxide (NO)-synthase pathway is present in skeletal muscle, vascular smooth muscle, and motor nerve terminals. Effects of NO were previously studied in rat neuromuscular preparations receiving low (0.2 Hz) or high (200 Hz) frequencies of stimulation. The latter frequency has always induced tetanic fade. However, in these previous studies we did not determine whether NO facilitates or impairs the neuromuscular transmission in preparations indirectly stimulated at frequencies which facilitate neuromuscular transmission. Thus, the present study was carried out to examine the effects of NO in rat neuromuscular preparations indirectly stimulated at 5 and 50 Hz. The amplitude of muscular contraction observed at the end (B) of a 10-s stimulation was taken as the ratio (R) of that obtained at the start (A) (R = B/A). S-nitroso-N-acetylpenicillamine (200 µM), superoxide dismutase (78 U/ml) and L-arginine (4.7 mM), but not D-arginine (4.7-9.4 mM), produced an increase in R (facilitation of neurotransmission) at 5 Hz. However, reduction in the R value (fade of transmission) was observed at 50 Hz. N G-nitro-L-arginine (8.0 mM) antagonized both the facilitatory and inhibitory effects of L-arginine (4.7 mM). The results suggest that NO may modulate the release of acetylcholine by motor nerve terminals.

Antagonism by hemoglobin of effects induced by L-arginine in neuromuscular preparations from rats

Nitric oxide (NO)-synthase is present in diaphragm, phrenic nerve and vascular smooth muscle. It has been shown that the NO precursor L-arginine (L-Arg) at the presynaptic level increases the amplitude of muscular contraction (AMC) and induces tetanic fade when the muscle is indirectly stimulated at low and high frequencies, respectively. However, the precursor in muscle reduces AMC and maximal tetanic fade when the preparations are stimulated directly. In the present study the importance of NO synthesized in different tissues for the L-Arg-induced neuromuscular effects was investigated. Hemoglobin (50 nM) did not produce any neuromuscular effect, but antagonized the increase in AMC and tetanic fade induced by L-Arg (9.4 mM) in rat phrenic nerve-diaphragm preparations. D-Arg (9.4 mM) did not produce any effect when preparations were stimulated indirectly at low or high frequency. Hemoglobin did not inhibit the decrease of AMC or the reduction in maximal tetanic tension induced by L-Arg in preparations previously paralyzed with d-tubocurarine and directly stimulated. Since only the presynaptic effects induced by L-Arg were antagonized by hemoglobin, the present results suggest that NO synthesized in muscle acts on nerve and skeletal muscle. Nevertheless, NO produced in nerve and vascular smooth muscle does not seem to act on skeletal muscle

Effects of intraperitoneal administration of khat extract in albino rats on uterine, vas deferens and phrenic diaphragm

The present study was conducted on normal adult albino rats of both sexes. Their body weight ranged between 200 and 250 gm and the experimental animals received 0.2 ml khat extract by intraperitoneal injection for 5 successive days. The mean height of uterine contractions in the pregnant and non-pregnant control groups were 3.48 +/- 1.244 cm and 1 +/- 0.28 cm respectively and were significantly reduced in the experimental pregnant and non-pregnant groups to 2.2 +/- 0.5 m and 0.33 +/- 0.15 cm respectively. The mean height of vas deferens contractions in the control group was 4.3 +/- 0.836 cm and was significantly reduced in the experimental group to 1.5 +/- 0.547 cm. In the control male group, the mean height of phrenic diaphragm contractions produced by direct and indirect stimulation were 5.8 +/- 0.5 cm and 3.7 +/- 0.8 cm respectively and were reduced significantly in the experimental group to 3.5 +/- 1.2 cm and to 1.4 +/- 0.4 cm. In the control female non-pregnant group the phrenic diaphragm contractions produced by direct and indirect stimulation were 4.8 +/- 0.8 cm and 2.9 +/- 0.5 cm respectively, and were reduced significantly in the experimental group to 3 +/- 1.2 cm and to 1.2 +/- 0.2 cm. In the control pregnant group, the phrenic diaphragm contractions produced by direct and indirect stimulation were 4 +/- 0.6 cm and 2.4 +/- 0.4 cm respectively and were significantly reduced in the experimental group to 1.2 +/- 0.2 cm and to 0.8 +/- 0.3 cm. The results were discussed

Membrane stabilizing action of cardio-selective Beta-adrenergic blocking agent [acebutolol] on the electrically stimulated diaphragmatic tissue of the rat

Isolated diaphragm of albino rats was prepared and effect of electric stimulation was observed before and after treatment of the tissue with the cardioselective beta-adrenergic blocking agent, acebutolol. Acebutolol did not produce no Significant effect on the response of tissue to electric stimulation in small doses. But in high dose, there was marked pression of the contractile effect of tissue to electric stimulation. It is concluded that this effect of acebutolol in high uses is due to the membrane stabilizing action of the drug

Metil-eugenol: uma avaliaçäo laboratorial em animais / Methyl eugenol: laboratory evaluation in animals

O metil-eugenol (C11H14O2), peso molecular igual a 178 g, fraçäo oleosa essencial obtida da planta Caryophyllus aromaticus L, conhecida popularmente como "Craveiro-da-índia", provocou efeitos depressores centrais, com significativa açäo hipnótica e miorrelaxante nas doses de 40 mg.Kg-1 intraperitoneal para ratos e 5 mg.Kg-1 por via venosa para coelhos e cäes. Observamos tempo de induçäo rápido e duraçäo satisfatória do sono (118 ñ 4s e 47 ñ 3 min para ratos, respectivamente) e tempo de sono entre 9 e 12 minutos para coelhos e cäes. A evoluçäo anestésica em cäes mostrou resultados satisfatório, seguido de rápida recuperaçäo, com conseqüente deambulaçäo. O metil-eugenol (20 microng.ml-1) produziu reduçäo de 50% da força de contraçäo da musculatura atrial cardíaca ao final de 15 min, sem alteraçäo da freqüência cardíaca, cujos efeitos näo foram bloqueados pela atropina (25 microng.ml-1) e prontamente revertidos após lavagem. Na preparaçäo nervo frênico-músculo diafragma de rato o metil-eugenol (40 microng.ml-1) foi capaz de bloquear completamente as contraçöes musculares produzidas tanto por estímulo direto quanto por estímulo indireto, semelhantes ao efeito da lidocaína (200 microng.ml-1). Todos os efeitos foram revertidos após lavagem. Os autores concluem que o metil eugenol apresentou resultados significativos e pode vir a ser usado, alternativamente, em experimentos com animais de laboratório

The effect of centrophenoxine at the skeletal neuromuscular junction.

Centrophenoxine exhibited some interesting actions at the neuromuscular junction. The drug was ineffective in rat or chick preparations, but blocked neuromuscular transmission in frog preparations. The blockade was reversed by adrenaline, potassium, choline and physostigmine. The drug had no effect on muscle contractility or endplate cholinoceptor. Hemicholinium 3 induced a neuromuscular blockade in rat (in vivo) which was reversed by choline but not by centrophenoxine. Neither of these two drugs could reverse the blocking effect of hemicholinium in frog preparations. It is concluded that centrophenoxine acts only in frog and the blockade involves a presynaptic mechanism. The work further suggests that choline uptake systems in the rat and the frog may not be identical, since choline competed with hemicholinium for the uptake system in rat and with centrophenoxine (but not with hemicholinium) in the frog.