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

Quando da utilização de bloqueadores neuromusculares, já foi enfatizado na literatura médica humana, que é de vital imporância a monitoração do bloqueio neuromuscular e que estes agentes nunca devem ser utilizados sem a mesma. O objetivo deste estudo foi o de avaliar o uso do monitor da transmissão neuromuscular TOF-Guard em eqüinos. Para tanto, doze eqüinos foram separados aleatoriamente para receberem como bloqueadores neuromusculares o pancurônio ou o atracúrio. Todos os eqüinos foram pré-medicados com romifidina, induzidos com diazepam e quetamina e mantidos com halotano. Foi administrado o atracúrio ou o pancurônio, seguindo-se a apnéia e início da ventilação mecânica controlada. O tempo entre a administração do relaxante muscular e a obtenção de um bloqueio máximo (T1=0), o retorno do T1 para 25% e da razão do TOF para 0,7 e o tempo do retorno do T1 de 25 para 75% foram mensurados. Concluiu-se que é de grande importância a monitoração do bloqueio neuromuscular quando da utilização de um bloqueador neuromuscular não-despolarizante, uma vez que ela torna o ato anestésico e cirúrgico mais seguro, com a utilização de doses adequadas que inviabilizam a superficialização do bloqueio durante o procedimento cirúrgico. O monitor TOF-Guard mostrou ser uma boa opção para a monitoração do bloqueio neuromuscular em eqüinos.

Intraocular pressure evaluation of equines anesthetized with romifidine, tiletamine/zolazepam, halothane and vecuronium

O objetivo deste estudo foi o de avaliar uma associação anestésica com e sem a utilização de relaxante muscular não-despolarizante e seu efeito sobre a pressão intra-ocular de eqüinos. Também objetivou-se uma técnica anestésica sem efeitos adversos que possa ser utilizada em procedimentos e cirurgias oftálmicas nesta espécie animal. Para tanto, dezesseis eqüinos foram divididos aleatoriamente em dois grupos de oito animais cada. Os animais do grupo I foram pré-medicados com romifidina, induzidos com tiletamina/zolazepam e a anestesia foi mantida com halotano e vecurônio. Os animais do grupo II receberam a mesma associação anestésica, com exceção do vecurônio. No decorrer do experimento, a pressão intra-ocular, a pressão arterial e a freqüência cardíaca foram avaliadas em diferentes momentos. A associação anestésica composta pela romifidina, tiletamina/ zolazepam e halotano com e sem vecurônio não promoveu alterações estatisticamente significativas na pressão intra-ocular de eqüinos e o seu uso é exeqüível em procedimentos oftálmicos nesta espécie animal.

Tempo de latencia do rocuronio e da succinilcolina e condicoes de intubacao traqueal

Background and Objectives - Pulmonary aspiration of gastric content during induction of anesthesia for emergency surgical procedures is a serious complication; fast endotracheal intubation under these circumstances is of vital importance to secure the airways. Despite its numerous side effects, succinylcholine is used for this purpose. Rocuronium is the most recently introduced aminoesteroid neuromuscular blocking drug with short onset. The objective of this study was to compare the onset time and intubating conditions of rocuronium and succinylcholine. Methods - After informed consent, forty-five patients were randomly allocated into three groups of 15: Group I (GI) = succinylcholine 1 mg.kg-1; Group II (GII) = rocuronium 0.6 mg.kg-1; Group III (GIII) = rocuronium 0.9 mg.kg-1. Every patient was premedicated with midazolam 15 mg per os and induction of anesthesia was made with fentanyl 10 μg.kg-1 and etomidate 0.3 mg.kg-1. The neuromuscular block was monitored with the TOP-Guard neuromuscular transmission monitor. The TOP-Guard neuromuscular monitor uses an accelerometer to measure the response to nerve stimulation. The stimulating electrodes were placed close to the course of the ulnar nerve at the wrist. The onset time was considered as the time between the end of neuromuscular drug injection and the twitch height (T1) decrease to 10%. Heart rate and arterial blood pressure were registered at 6 moments before and after induction of anesthesia. Results - The onset time results were: Group I, 71 s; Group II, 120 s and Group III, 70 s or GI = GIII < GII (F = 8.862; p < 0.01). There were 43 patients exhibiting excellent intubating conditions and 2 with good intubating conditions. Heart rate and arterial blood pressure showed alterations due to induction of anesthesia and intubation. Conclusions - Rocuronium 0.9 mg.kg-1 can be used in rapid sequence induction because it has a short onset time which is similar to that of succnylcholine. It is likely that rocuronium would be a good indication in patients with high intracranial pressure, burns and neuromuscular diseases.

Analysis of rocuronium in human plasma by liquid chromatography-tandem mass spectrometry with application in clinical pharmacokinetics

Rocuronium (ROC) is a neuromuscular blocking agent used in surgical procedures which is eliminated primarily by biliary excretion. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for analysis of ROC in human plasma. Separation of ROC and IS (verapamil) was performed using an endcapped C-18 column and a mixture of water:acetonitrile:trifluoracetic acid (50:50:0.1, v/v) as mobile phase. Aliquots of 100 mu L of human plasma were extracted at pH 3, using dichloromethane. The lower limit of quantification of 5 ng/mL shows the high sensitivity of this method. Intra- and inter-assay precision (as relative standard deviation) was all <= 14.2% and accuracy (as relative standard error) did not exceed 10.1%. The validated method was successfully applied to quantify ROC concentrations in patients under surgical procedures up to 6 h after the administration of the 0.4-0.9 mg/kg ROC. The pharmacokinetic parameter estimations of ROC showed AUC/dose of 563 mu g min/mL, total clearance of 2.5 mL/min/kg, volume of distribution at steady state of 190 mL/kg and mean residence time of 83 min. (C) 2013 Elsevier B.V. All rights reserved.

Anestesia peribulbar com ropivacaína como alternativa ao bloqueio neuromuscular para facectomia em cães

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Neutralization of snake venom phospholipase A(2) toxins by aqueous extract of Casearia sylvestris (Flacourtiaceae) in mouse neuromuscular preparation

Aqueous extract of Casearia sylvestris (Flacourtiaceae) has been shown to inhibit enzymatic and biological properties of some Bothrops and Crotalus venoms and their purified phospholipase A(2) (PLA(2)) toxins. In this work we evaluated the influence of C sylvestris aqueous extract upon neuromuscular blocking and muscle damaging activities of some PLA(2)S (crotoxin from C. durissus terrificus, bothropstoxin-I from B.jararacussu, piratoxin-I from B. pirajai and myotoxin-II from B. moojeni) in mouse phrenic-diaphragm preparations. Crotoxin (0.5 mu M) and all other PLA2 toxins (1.0 mu M) induced irreversible and time-dependent blockade of twitches. Except for crotoxin, all PLA2 toxins induced significant muscle damage indices, assessed by microscopic analysis. Preincubation of bothropstoxin-I, piratoxin-I or myotoxin-II with C. sylvestris extract (1:5 (w/w), 30 min, 37 degrees C significantly prevented the neuromuscular blockade of preparations exposed to the mixtures for 90 min; the extent of protection ranged from 93% to 97%. The vegetal extract also neutralized the muscle damage (protection of 80-95%). Higher concentration of the C. sylvestris extract (1: 10, w/w) was necessary to neutralize by 90% the neuromuscular blockade induced by crotoxin. These findings expanded the spectrum of C. sylvestris antivenom activities, evidencing that it may be a good source of potentially useful PLA2 inhibitors. (c) 2007 Elsevier B.V.. All rights reserved.

Understanding the in vitro neuromuscular activity of snake venom Lys49 phospholipase A(2) homologues

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Caracterização das atividades de PLA2s Lys49, isoladas de venenos de serpentes do gênero Bothrops, em preparação neuromuscular de camundongos e influência de agentes neutralizadores

Pós-graduação em Ciências Biológicas (Farmacologia) - IBB

Efeito do propofol associado à efedrina no tempo de latência do cisatracúrio

OBJETIVOS: Este estudo teve por objetivo avaliar a eficácia da efedrina na prevenção dos efeitos hemodinâmicos induzidos pela associação do propofol e do remifentanil, assim como os efeitos sobre o tempo de latência do cisatracúrio. MÉTODOS: Sessenta pacientes com idade entre 18 e 52 anos, estado físico ASA I ou II, foram divididos em três grupos, aleatoriamente: G I - propofol 1%; G II - propofol 1% + efedrina 0,5 mg.ml-1 e G III - propofol 1% + efedrina 1,0 mg.ml-1 (velocidade de infusão igual a 180 ml.h-1), até a perda da consciência. Administrou-se remifentanil (0,5 mg.kg-1.min-1) e cisatracúrio na dose de 0,15 mg.kg-1. Foram registrados os dados demográficos, os sinais vitais (PAS, PAM, PAD, FC e SpO2) e o tempo de latência do cisatracúrio. RESULTADOS: Os grupos foram homogêneos com relação aos dados demográficos. Houve diminuição estatisticamente significativa dos valores de PAS, PAM, PAD e FC, um e três minutos após a administração do propofol, porém sem significado clínico importante e sem diferença entre os grupos. As medianas para os tempos de latência do cisatracúrio foram: 178 s (G2 e G3) e 183 s (G1), mas sem diferença significante entre os grupos. CONCLUSÃO: Não houve diminuição clinicamente importante dos parâmetros hemodinâmicos avaliados nos grupos que receberam ou não a efedrina e o tempo de latência do cisatracúrio foi o mesmo para os diferentes grupos.

INJECTION OF RAMIPRIL INTO THE LATERAL VENTRICLE INTERFERES WITH THE DRINKING RESPONSE INDUCED BY PHARMACOLOGICAL AND NATURAL THIRST STIMULI

We investigated the effects of ramipril, an angiotensin I-converting enzyme (ACE) inhibitor, on water intake by male Holtzman rats (250-300 g) with cannulae implanted into the lateral ventricle. Intracerebroventricular (icv) injection of ramipril (1 mu g/mu l) significantly reduced drinking in response to subcutaneous (sc) injection of isoprenaline (100 mu g/kg) from 8.49 +/- 0.69 to 2.96 +/- 0.36 ml/2 h, polyethyleneglycol (PEG) (30% w/v, 10 ml/kg) from 9.51 +/- 2.20 to 1.6 +/- 0.34 ml/2 h or water deprivation for 24 h from 12.61 +/- 0.83 to 5.10 +/- 1.37 ml/2 h. Ramipril had no effect on water intake induced by cellular dehydration produced by sc injection of hypertonic saline (2 M NaCl). These results are consistent with the hypothesis that ramipril acts as an ACE-blocking agent in the brain. The possibility that ramipril is transformed to ramiprilat, the active drug, by the brain is suggested.

THE USE OF AMPPD AS AN ALTERNATIVE SUBSTRATE FOR AP-MEDIATED DETECTION OF NONRADIOLABELED DNA PROBES IN EUCALYPTUS-SALIGNA

We present a non-radioactive alternative to Southern's (J. Mol. Biol. 98: 503-517, 1975) DNA-DNA hybridization technique. The use of AMPPD - Disodium 3-(4-Methoxyspiro {1,2-dioxetane-3,2'tricyclo[3.3.1.1(3,7)]decan}-4-yl)phyenyl phosphate as an alternative substrate for AP-mediated detection of digoxigenin-11 dUTP-labeled probes made possible the simple and nonhazardous reuse of blots. We used 0.8 % agarose gels containing 30 mug per lane of Eucalyptus saligna DNA, digested with Eco RI, electrophoresed and blotted on to nylon membranes (Hybond-N, Amersham, UK), using the Southern blotting procedure, and UV irradiated for one minute for DNA fixation. The hybridizations were carried out overnight with digoxigenin labeled random inserts of E. saligna DNA by using the Genius Kit (Boehringer Mannheim). Detection of the DNA-DNA hybrids was performed in the presence of 0.5% blocking agent and the substrates NBT/BCIP were replaced by 0.26 mM AMPPD in the final alkaline assay buffer (50 mul/cm2). After membrane incubation for five minutes at room temperature in a sealed plastic bag, the AMPPD solution was retrieved and stored at 4-degrees-C for reuse. A Kodak X-BRAF QA-S film was pressed firmly onto the bag containing the wet membrane, exposed for two to six hours and then developed. After use, the probes were stripped off and the blots reutilized, three times so far, with the same results.

Interaction between vitamin K nutriture and bacterial overgrowth in hypochlorhydria induced by omeprazole

Subjects taking a hydrogen pump blocking agent (omeprazole) develop bacterial overgrowth of the small intestine. We tested the hypothesis that this bacterial overgrowth produces menaquinones, which would meet the Vitamin requirement in situations of vitamin K deficiency. In a crossover-type design, 13 healthy Volunteers eating a phylloquinone-restricted diet for 35 d were randomly assigned to take omeprazole during the first period of study or starting on day 15 until the end of the study. Coagulation times, serum osteocalcin [total osteocalcin and undercarboxylated osteocalcin (ucOC)], plasma phylloquinone, urinary gamma-carboxyglutamic acid, and plasma undercarboxylated prothrombin (PIVKA-II) were measured. Plasma phylloquinone concentrations declined 82% with dietary phylloquinone restriction (P < 0.05) and were not significantly different in the period when the diet was combined with omeprazole treatment (P > 0.05), the mean value for PIVKA-II during the phylloquinone-restricted diet significantly increased 5.7-fold from baseline (P < 0.05); however, the combination of omeprazole treatment and the phylloquinone-restricted diet significantly reduced PIVKA-II values by 21% (P < 0.05) compared with the diet period alone. There were no alterations in total or percentage ucOC concentrations during the phylloquinone-restricted diet or during the period of diet plus omeprazole treatment. Our data support the hypothesis that bacterial overgrowth results in the synthesis and absorption of menaquinones. These menaquinones contribute to vitamin K nutriture during dietary phylloquinone restriction, but not enough to restore normal vitamin K status.