Cardioneuroablación como tratamiento del síncope reflejo: reporte de un caso

Resumen: El síncope mediado neuralmente es un trastorno causado por un reflejo autónomo anormalmente amplificado que involucra componentes tanto simpáticos como parasimpáticos. Es la causa más frecuente de síncope en personas jóvenes y su tratamiento sigue siendo un desafío, ya que no se ha demostrado que alguna terapia farmacológica prevenga por completo su recurrencia. En los últimos años ha surgido una técnica denominada cardioneuroablación, que consiste en la ablación por radiofrecuencia de los plexos ganglionares (PG) parasimpáticos, con buenos resultados a corto y largo plazo en la prevención de síncope recurrente, según los diferentes grupos de investigación. Presentamos el primer caso en Chile de un hombre joven con síncopes mediados neuralmente recurrentes que fue tratado con esta técnica en el Hospital Regional de Concepción.

Abstract: Cardioneuroablation is a novel method that can be used to treat reflex syncope. Although the experience with this technique is relatively limited it provides a more physiological way to treat this condition. The first case in Chile is herein reported along with a discussion of the subject.

Acute exercise inhibits gastric emptying of liquids in rats: influence of the NO-cGMP pathway

We previously found that acute exercise inhibited the gastric emptying of liquid in awake rats by causing an acid-base imbalance. In the present study, we investigated the involvement of the nitric oxide-cyclic guanosine monophosphate (NO-cGMP) pathway, vasoactive intestinal peptide (VIP), and corticotropin-releasing factor (CRF) peptide in this phenomenon. Male rats were divided into exercise or sedentary group and were subjected to a 15-min swim session against a load (2.5 or 5% b.w.). The rate of gastric emptying was evaluated after 5, 10, or 20 min postprandially. Separate groups of rats were treated with vehicle (0.9% NaCl, 0.1 mL/100 g, ip) or one of the following agents: atropine (1.0 mg/kg, ip), the NO non-selective inhibitor Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME; 10.0 mg/kg, ip), or the selective cGMP inhibitor 1H-(1,2,4)oxadiazole[4,3-a]quinoxalin-1-one (ODQ; 5.0 mg/kg, ip), the i-NOS non-specific inhibitor (aminoguanidine; 10.0 mg/kg, ip), the corticotropin-releasing factor receptor antagonist (astressin; 100 µg/kg, ip), or the vasoactive intestinal peptide (VIP) receptor antagonist Lys1, Pro2,5, Arg3,4, Tyr6 (100 µg/kg, ip). Compared to sedentary rats, both the 2.5 and 5% exercise groups exhibited higher (P<0.05) values of blood lactate and fractional gastric dye recovery. Corticosterone and NO levels increased (P<0.05) in the 5% exercised rats. Pretreatment with astressin, VIP antagonist, atropine, L-NAME, and ODQ prevented the increase in gastric retention caused by exercise in rats. Acute exercise increased gastric retention, a phenomenon that appears to be mediated by the NO-cGMP pathway, CRF, and VIP receptors.

Acetylcholine produces contractions mediated by the cyclooxygenase pathway in arterial vessels in the Chilean frog (Calyptocephalella gayi) / Acetilcolina produz contrações mediadas pela via da ciclooxigenase em vasos arteriais da rã chileno (Calyptocephalella gayi)

Abstract Previous studies performed in marine fish (I. conceptionis and G. laevifrons) showed that indomethacin blocked arterial contraction mediated by acetylcholine (ACh). The objective of this study was to determine if contraction induced by acetylcholine is mediated by the cyclooxygenase pathway in several arterial vessels in the Chilean frog Calyptocephalella gayi. Arteries from the pulmonary (PA), dorsal (DA), mesenteric (MA) and iliac (IA) regions were dissected from 6 adult specimens, and isometric tension studies were done using dose response curves (DRC) for ACh (10-13 to 10-3 M) in presence of a muscarinic antagonist (Atropine 10-5 M) and an unspecific inhibitor of cyclooxygenases (Indomethacin, 10-5M). All the studied arteries exhibited vasoconstriction mediated by ACh. This vasoconstriction was abolished in the presence of atropine in DA, MA and IA and attenuated in PA. Indomethacin abolished the vasoconstriction in MA and attenuated the response in PA, DA and IA. Similar to marine fish, C. gayi have an ACh-mediated vasoconstrictor pattern regulated by muscarinic receptors that activate a cyclooxygenase contraction pathway. These results suggest that the maintenance in vasoconstrictor mechanisms mediated by ACh→COX →vasoconstriction is conserved from fish to frogs.

Resumo Estudos feitos em peixes marinhos (I. conceptionis e G. laevifrons) têm demostrado que a indometacina bloqueia a contração arterial mediada por acetilcolina (ACh). O objetivo do presente estudo foi avaliar o efeito da via da ciclooxigenase na contração induzida por ACh em vasos arteriais da rã chilena Calyptocephalella gayi. Foram dissecadas regiões das artérias pulmonares (PA), dorsal (DA), mesentérica (MA) e ilíaca (IA) de seis espécimes adultos e realizados estudos de tensão isométrica utilizando curvas dose-resposta (CDR) de ACh (10-13 a 10-3 M) na presença de um antagonista muscarínico (atropina, 10-5 M) e um inibidor das ciclooxigenases (indometacina, 10-5 M). Todas as artérias evidenciaram uma resposta vasoconstritora mediada por ACh. Esta resposta vasoconstrictora foi suprimida na presença de atropina nas artérias DA, MA, IA e atenuada na PA. A indometacina suprimiu a vasoconstrição na artéria MA e atenuou a resposta nas artérias PA, DA e IA. Tal como os peixes marinhos, a C. gayi tem um padrão de vasoconstrição mediado por Ach que é regulado pelos receptores muscarínicos e pela ciclooxigenase. Estes resultados sugerem a conservação dos mecanismos vasoconstrictores mediados por ACh→COX em peixes e rãs.

Dipyrone in association with atropine inhibits the effect on gastric emptying induced by hypoglycemia in rats

Atropine (AT) and dipyrone (Dp) induce a delay of gastric emptying (GE) of liquids in rats by inhibiting muscarinic receptors and activating β2-adrenergic receptors, respectively. The objective of the present study was to determine the effects of pretreatment with AT and Dp, given alone or in combination, on the effect of hypoglycemia in the liquid GE in rats. Male Wistar adult rats (280-310 g) were pretreated intravenously with AT, Dp, AT plus Dp or their vehicle and then treated 30 min later with iv insulin or its vehicle (n=8-10 animals/group). Thirty min after treatment, GE was evaluated by determining, in awake rats, the percent gastric retention (%GR) of a saline meal labeled with phenol red administered by gavage. The results indicated that insulin induced hypoglycemia in a dose-dependent manner resulting in a significant reduction in %GR of liquid only at the highest dose tested (1 U/kg). Pretreatment with AT significantly increased %GR in the rats treated with 1 U/kg insulin. Surprisingly, after pretreatment with AT, the group treated with the lowest dose of insulin (0.25 U/kg) displayed significantly lower %GR compared to its control (vehicle-treated group), which was not seen in the non-pretreated animals. Pretreatment with Dp alone at the dose of 40 mg/kg induced an increase in %GR in both vehicle and 0.25 U/kg-treated rats. A higher dose of Dp alone (80 mg/kg) significantly reduced the effect of a marked hypoglycemia induced by 1 U/kg of insulin on GE while in combination with AT the effect was completely abolished. The results with AT suggest that moderate hypoglycemia may render the inhibitory mechanisms of GE ineffective while Dp alone and in combination with AT significantly overcame the effect of hypoglycemia on GE.

Pharmacological study of the mechanisms involved in the vasodilator effect produced by the acute application of triiodothyronine to rat aortic rings

A relationship between thyroid hormones and the cardiovascular system has been well established in the literature. The present in vitro study aimed to investigate the mechanisms involved in the vasodilator effect produced by the acute application of 10-8–10-4 M triiodothyronine (T3) to isolated rat aortic rings. Thoracic aortic rings from 80 adult male Wistar rats were isolated and mounted in tissue chambers filled with Krebs-Henseleit bicarbonate buffer in order to analyze the influence of endothelial tissue, inhibitors and blockers on the vascular effect produced by T3. T3 induced a vasorelaxant response in phenylephrine-precontracted rat aortic rings at higher concentrations (10-4.5–10-4.0 M). This outcome was unaffected by 3.1×10-7 M glibenclamide, 10-3 M 4-aminopyridine (4-AP), 10-5 M indomethacin, or 10-5 M cycloheximide. Contrarily, vasorelaxant responses to T3 were significantly (P<0.05) attenuated by endothelium removal or the application of 10-6 M atropine, 10-5 M L-NG-nitroarginine methyl ester (L-NAME), 10-7 M 1H-(1,2,4)oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), 10-6 M (9S,10R,12R)-2,3,9,10,11,12-Hexahydro-10-methoxy-2,9-dimethyl-1-oxo-9,12-epoxy-1H-diindolo[1,2,3-fg:3′,2′,1′-kl]pyrrolo[3,4-i](1,6)benzodiazocine-10-carboxylic acid, methyl ester KT 5823, 10-2 M tetraethylammonium (TEA), or 10-7 M apamin plus 10-7 M charybdotoxin. The results suggest the involvement of endothelial mechanisms in the vasodilator effect produced by the acute in vitro application of T3 to rat aortic rings. Possible mechanisms include the stimulation of muscarinic receptors, activation of the NO-cGMP-PKG pathway, and opening of Ca2+-activated K+ channels.

Acetylcholine produces contraction mediated by cyclooxigenase pathway in arterial vessels in the marine fish (Isacia conceptionis) / Função vascular nas artérias do peixe marinos Isacia conceptionis

Preliminary studies showed that dorsal artery contraction mediated by acetylcholine (ACh) is blocked with indomethacin in intertidal fish (G. laevifrons). Our objective was to characterize the cholinergic pathway in several artery vessels of the I. conceptionis. Afferent and efferent branchial, dorsal and mesenteric arteries were dissected of 6 juvenile specimens, isometric tension studies were done using doses response curves (DRC) for Ach (10–13 to 10–3 M), and cholinergic pathways were obtained by blocking with atropine or indomethacin. CRC to ACh showed a pattern of high sensitivity only in efferente branchial artery and low sensibility in all vessels. Furthermore, these contractions were blocked in the presence of atropine and indomethacin in all vessels. Our results corroborate previous results observed in intertidal species that contraction induced by acetylcholine is mediated by receptors that activate a cyclooxygenase contraction pathway.

Estudos preliminares mostraram que a contração da artéria dorsal mediada por acetilcolina (ACh) é bloqueada com indometacina em peixes marinhos (G. laevifrons). Nosso objetivo foi caracterizar a via colinérgica em várias artérias de I. conceptionis. Artérias aferentes e eferentes branquiais, dorsais e mesentéricas foram dissecadas de 6 espécimes juvenis. Os estudos de tensão isométrica foram feitos utilizando-se a curva dose - resposta (CDR) para Ach (10–13 a 10–3M), e identificaram-se as vias colinérgicas, bloqueando com atropina e indometacina. CRC para ACh mostrou um padrão de alta sensibilidade na artéria eferentes branquiais e baixa sensibilidade em todos os vasos sanguineos. Essas contrações foram bloqueadas na presença de atropina e indometacina em todas as artérias avaliadas. Nossos resultados confirmam que a contração induzida por acetilcolina é mediada por receptores muscarínicos que ativam ciclo-oxigenase.

Modulatory effects of taurine on jejunal contractility

Taurine (2-aminoethanesulfonic acid) is widely distributed in animal tissues and has diverse pharmacological effects. However, the role of taurine in modulating smooth muscle contractility is still controversial. We propose that taurine (5-80 mM) can exert bidirectional modulation on the contractility of isolated rat jejunal segments. Different low and high contractile states were induced in isolated jejunal segments of rats to observe the effects of taurine and the associated mechanisms. Taurine induced stimulatory effects on the contractility of isolated rat jejunal segments at 3 different low contractile states, and inhibitory effects at 3 different high contractile states. Bidirectional modulation was not observed in the presence of verapamil or tetrodotoxin, suggesting that taurine-induced bidirectional modulation is Ca2+ dependent and requires the presence of the enteric nervous system. The stimulatory effects of taurine on the contractility of isolated jejunal segments was blocked by atropine but not by diphenhydramine or by cimetidine, suggesting that muscarinic-linked activation was involved in the stimulatory effects when isolated jejunal segments were in a low contractile state. The inhibitory effects of taurine on the contractility of isolated jejunal segments were blocked by propranolol and L-NG-nitroarginine but not by phentolamine, suggesting that adrenergic β receptors and a nitric oxide relaxing mechanism were involved when isolated jejunal segments were in high contractile states. No bidirectional effects of taurine on myosin phosphorylation were observed. The contractile states of jejunal segments determine taurine-induced stimulatory or inhibitory effects, which are associated with muscarinic receptors and adrenergic β receptors, and a nitric oxide associated relaxing mechanism.

Vascular function in arteries of intertidal fish Girella laevifrons (Kyphosidae) / Função vascular nas artérias do peixe marinho Girella laevifrons (Kyphosidae)

Preliminary studies showed that dorsal artery contraction mediated by acetylcholine (ACh) is blocked with indomethacin in intertidal fish (Girella laevifrons). Our objective was to characterise the cholinergic pathway in several artery vessels of the G. laevifrons. Afferent and efferent branchial, dorsal and mesenteric arteries were dissected of 6 juvenile specimens, isometric tension studies were done using dose response curves (DRC) for Ach (10–13 to 10–3 M), and cholinergic pathways were obtained by blocking with atropine or indomethacin. CRC to ACh showed a pattern of high and low sensitivity. Furthermore, these contractions were blocked in the presence of atropine and indomethacin in all vessels. Our results suggest that contraction observed with acetylcholine is mediated by receptors that activate a cyclooxygenase contraction pathway.

Estudos preliminares mostraram que a contração da artéria dorsal mediada por acetilcolina (ACh) é bloqueada com indometacina em peixes marinhos Girella laevifrons. Nosso objetivo foi caracterizar a via colinérgica em várias artérias de G. laevifrons. Artérias aferentes e eferentes branquiais, dorsais e mesentéricas foram dissecadas de 6 espécimes juvenis. Os estudos de tensão isométrica foram feitos utilizando-se a curva dose - resposta (CDR) para Ach (10–13 a 10–3M), e identificaram-se as vias colinérgicas, bloqueando com atropina e indometacina. CRC para ACh mostrou um padrão de alta e baixa sensibilidade. Essas contrações foram bloqueadas na presença de atropina e indometacina em todas as artérias avaliadas. Nossos resultados sugerem que a contração observada com acetilcolina é mediada por receptores muscarínicos que ativam uma ciclo-oxigenase.

Cetamina, xilazina e atropina, em doses calculadas por extrapolação alométrica interespecífica, para contenção farmacológica da cutia (Dasyprocta azarae) / Allometrically scaled dosages of ketamine, xylazine and atropine for chemical restraint of agouti (Dasyprocta azarae) / Ketamina, xilacina y atropina, en dosis calculadas por extrapolación alométrica interespecífica, para sujeción farmacológica del agutí (Dasyprocta azarae)

A cutia (Dasyprocta azarae) é um roedor neotropical que necessita ser contido por meios farmacológicos para a realização de certos procedimentos médicos e de manejo, em função de características comportamentais de defesa e grande susceptibilidade ao estresse. A combinação de cloridrato de cetamina, cloridrato de xilazina e sulfato de atropina foi administrada, por via intramuscular, a 53 cutias (33 machos e 20 fêmeas) com pesos entre 0,74 e 3,58 kg (2,071±0,678 kg), para possibilitar a realização de procedimentos de campo que incluíam determinação de sexo, biometria, marcação, exame físico e colheita de sangue e urina. Após a pesagem de cada cutia, a dose individual de cada um dos fármacos foi calculada por meio de extrapolação alométrica interespecífica, usando-se como modelo as doses usualmente recomendadas para um cão doméstico de 10 kg (cetamina – 20,00mg/kg, xilazina – 2,00mg/kg e atropina – 0,05mg/kg). Em todos os animais a indução do estado de contenção foi rápida, sendo a reação postural de endireitamento abolida entre 0,5 e 5,0 minutos (2,02±1,21 minutos) após a injeção. A temperatura retal variou de 28,9 a 40,9ºC (36,38±2,04ºC), a frequência cardíaca variou de 72 a 240 b.p.m. (150,93±31,48 b.p.m.) e a frequência respiratória variou de 20 a 192 m.p.m. (80,63±29,09 m.p.m.). Avaliou-se a qualidade da contenção farmacológica com base no miorrelaxamento observado aos dez, 15, 25 e 35 minutos após a injeção. A contenção farmacológica foi excelente em cerca de 90,00% dos casos, e boa em outros 5,00%. A qualidade da analgesia foi avaliada, principalmente, por meio das rea- ções de nocicepção ao pinçamento de um dígito do membro torácico esquerdo aos dez, 15, 25 e 35 minutos após a injeção, e foi ruim em mais de 50,00% dos casos...

The agouti (Dasyprocta azarae) is a neotropical rodent that requires chemical restraint for handling due to its susceptibility to stress and defensive behavior characteristics. Fifty-three agoutis (33 males and 20 females) weighing 0.74 to 3.58 kg (2.071±0.678 kg) were given ketamine hydrochloride, xylazine hydrochloride and atropine sulfate combined by i.m. injection during field procedures that included sexing, measuring, marking, physical examinations and collecting blood and urine. All drug doses were calculated using the respective doses of a 10-kg dog as model. These doses are 20.00 mg/ kg for ketamine, 2.00mg/kg for xylazine and 0.05mg/kg for atropine. In all individuals, immobilization was rapid and uneventful. Righting reflexes were abolished after 0.50 to 5.00 min (2.02±1.21 min). Body temperature fluctuated between 28.9 and 40.9ºC (36.38±2.04ºC), heart rates remained between 72 and 240 beats/min (150.93±31.48); and respiratory rates ranged between 20 and 192 breaths/min (80.63±29.09). Restraint quality was evaluated by measuring muscle relaxation at 10, 15, 25 and 35 min after injection. Chemical restraint was excellent in about 90.00% and good in about 5.00% of the cases. Analgesia quality was evaluated mainly by measuring the reactions to painful stimuli such as pinching of a digit in the left thoracic limb at 10, 15, 25 e 35 min after injection, and was poor in more than 50.00% of the cases. Recovery occurred without psychomotor disturbances, and every animal remained calm until normal ambulation resumed between 105 and 277 min (164.94 ±37.14 min). The proposed method was safe for both animals and the human personnel. It is recommended for routine management and stressful but not painful medical procedures like physical examination, measuring, sexing, and urine and blood collection in D. azarae. This article rescues data obtained in an investigation performed back in 1998...

El agutí (Dasyprocta azarae) es un roedor neo tropical que necesita ser sujetado por medios farmacológicos para ciertos procedimientos médicos y de manejo, debido a características comportamentales de defensa y gran susceptibilidad a el estrés. La combinación de clorhidrato de ketamina, clorhidrato de xilacina y sulfato de atropina fue administrada por vía intramuscular a 53 agutíes (33 machos e 20 hembras) con pesos entre 0,74 e 3,58 kg (2,071±0,678 kg), para posibilitar la realización de procedimientos de campo que incluyan determinación de sexo, biometría, marcación, examen físico y colecta de sangre y orina. Cada animal fue pesado y la dosis individual de cada uno de los fármacos fue calculada por extrapolación alométrica interespecífica, usándose como modelo las dosis usualmente recomendadas para un perro doméstico de 10 kg (ketamina – 20,00mg/kg, xilacina – 2,00mg/kg y atropina – 0,05mg/kg). En todos los animales la inducción del estado de sujeción fue rápida, y la reacción postural de enderechamiento fue abolida entre 0,5 e 5,0 minutos (2,02±1,21 minutos) después de la inyección. La temperatura rectal varió de 28,9 a 40,9ºC (36,38±2,04ºC), la frecuencia cardíaca varió de 72 a 240 b.p.m. (150,93±31,48 b.p.m.) y la frecuencia respiratoria varió de 20 a 192 m.p.m. (80,63±29,09 m.p.m.). Se evaluó la calidad de la sujeción farmacológica, basado en el relajamiento muscular observado a los 10, 15, 25 y 35 minutos después de la inyección. La sujeción farmacológica fue excelente en casi 90,00% de los casos, y buena en otros 5,00%. La calidad de la analgesia fue evaluada principalmente por las reacciones de sensibilidad dolorosa al pinzamiento de un dígito del miembro torácico izquierdo a los 10, 15, 25 e 35 minutos después de la inyección, y fue ruin en más de 50,00% de los casos...

Effects of atropine and propranolol on lung inflammation in experimental envenomation: comparison of two buthidae venoms

Background: Previous works had shown that scorpion venom induced neurotransmitter elevation and an inflammatory response associated with various anatomo-pathological modifications. The most dangerous scorpions species in Algeria responsible for these effects are Androctonus australis hector (Aah) and Androctonus amoreuxi (Aam). Results: Comparison of the physiopathological effects induced by the two venoms showed differences in the kinetic of cytokine release and in lung injury. The lung edema was only observed in response to Aah venom and it was correlated with cell infiltration. In order to better understand the involved mechanism in inflammatory response, we used two antagonists, atropine (non-selective muscarinic antagonist) and propranolol (ß adrenergic antagonist), which lead to a decrease of cell infiltration but has no effect on edema forming. Conclusion: These results suggest another pathway in the development of lung injury following envenomation with Aam or Aah venom.(AU)

[Pharmaceutical effects of ephedrine, atropine and mucosal phenilephrin on hemodynamic alterations of women during spinal anesthesia in cesarean section]

Hemodynamic alteration and hypotension due to spinal anesthesia can reduce tissue perfusion and increase ischemic risk, myocardial infraction, renal failures spinal damages and even deep veins thrombosis. This study was designed to compare pharmaceutical effects of ephedrine, atropine and mucosal phenilephrin on hemodynamic alteration of women during spinal anesthesia in cesarean section. This randomized clinical and double blind study was done on 90 singleton pregnant women with ASA I and II class .the subjects gone elective cesarean section and allocated into three groups. subjects were received 500 ml ringer lactate before spinal anesthesia. Subjects in group I, II and III first received 0.1 mg/kg atropine [IV] 0.01mg/kg ephedrine and 100 micro gr phenilephrin [mucosal] prior spinal anesthesia, respectively. Hemodaynamic indexes including blood pressure, heart Rate, oxygen saturation and drug side effects were determined every 5 minutes interval through the surgery. Data was analyzed by using SPSS-11.5, Chi-Square and ANOVA tests. Hemodaynamic indexes were changed during study, but three medicine showed similar effect on heart Rate, blood pressure and changes of oxygen saturation [P<0.05]. There was a significant differences among three groups for dosage of extra ephedrine to control of blood pressure [P<0.05]. This increase dosage of extra ephedrine was 56.7%, 20% and in ephedrine, phenilephrin and atropine groups,respectively. Nosia rate was 6.7%, 50% and 46.7% in phenilephrin, atropine and ephedrine groups, respectively [P<0.05]. This study showed that to prevent of blood pressure drop following spinal anestasia atropine, phenilephrin and ephedrine can be prescribed, but ephedrine is recommended for lowering the rate of nosia

Noninvasive method for electrocardiogram recording in conscious rats: feasibility for heart rate variability analysis

Heart rate variability (HRV) analysis consists in a well-established tool for the assessment of cardiac autonomic control, both in humans and in animal models. Conventional methods for HRV analysis in rats rely on conscious state electrocardiogram (ECG) recording based on prior invasive surgical procedures for electrodes/transmitters implants. The aim of the present study was to test a noninvasive and inexpensive method for ECG recording in conscious rats, assessing its feasibility for HRV analysis. A custom-made elastic cotton jacket was developed to fit the rat's mean thoracic circumference, with two pieces of platinum electrodes attached on its inner surface, allowing ECG to be recorded noninvasively in conscious, restrained rats (n=6). Time- and frequency-domain HRV analyses were conducted, under basal and autonomic blockade conditions. High-quality ECG signals were obtained, being feasible for HRV analysis. As expected, mean RR interval was significantly decreased in the presence of atropine (p <0.05) and increased in the presence of propranolol (p<0.001). Also, reinforcing the reliability of the method, low- and high-frequency HRV spectral powers were significantly decreased in the presence of propranolol (p <0.05) and atropine (p< 0.001), respectively. In summary, the present work describes a novel, inexpensive and noninvasive method for surface ECG recording in conscious rats.

A análise da variabilidade da freqüência cardíaca (VFC) consiste em uma metodologia bem estabelecida para o estudo do controle autonômico cardíaco, tanto em humanos como em modelos animais. As metodologias convencionais para o estudo da VFC em ratos utilizam-se de procedimentos cirúrgicos para o implante de eletródios ou transmissores, o que possibilita a posterior aquisição do eletrocardiograma (ECG) no estado consciente. O objetivo do presente trabalho foi o de desenvolver e aplicar um método não-invasivo para o registro do ECG em ratos conscientes, verificando sua validade para a análise da VFC. Uma vestimenta de tecido elástico em algodão foi desenvolvida de acordo com as dimensões médias da circunferência torácica dos animais, e dois pequenos eletródios retangulares de platina foram aderidos à superfície interna da vestimenta, permitindo o registro do ECG de forma não-invasiva em ratos conscientes (n=6), sob contenção. Foram conduzidas análises de VFC nos domínios do tempo e da freqüência, tanto para a condição basal, como para as condições de bloqueio autonômico. Foram obtidos sinais de ECG de alta qualidade, viáveis para a análise de VFC. Conforme esperado, o intervalo RR médio foi significativamente reduzido na presença de atropina (p<0.05), e aumentado na presença de propranolol (p<0.001). Reforçando a validade do método, as potências espectrais de baixa e alta freqüência da VFC sofreram reduções significativas, respectivamente, na presença de propranolol (p<0.05) e atropina (p<0.05). Em resumo, o presente trabalho descreve um novo método, de baixo custo e natureza não-invasiva, para a realização do ECG de superfície em ratos conscientes.

Participation of the cholinergic system in the ethanol-induced suppression of paradoxical sleep in rats

Sleep disturbance is among the many consequences of ethanol abuse in both humans and rodents. Ethanol consumption can reduce REM or paradoxical sleep (PS) in humans and rats, respectively. The first aim of this study was to develop an animal model of ethanol-induced PS suppression. This model administered intragastrically (by gavage) to male Wistar rats (3 months old, 200-250 g) 0.5 to 3.5 g/kg ethanol. The 3.5 g/kg dose of ethanol suppressed the PS stage compared with the vehicle group (distilled water) during the first 2-h interval (0-2 h; 1.3 vs 10.2; P < 0.001). The second aim of this study was to investigate the mechanisms by which ethanol suppresses PS. We examined the effects of cholinergic drug pretreatment. The cholinergic system was chosen because of the involvement of cholinergic neurotransmitters in regulating the sleep-wake cycle. A second set of animals was pretreated with 2.5, 5.0, and 10 mg/kg pilocarpine (cholinergic agonist) or atropine (cholinergic antagonist). These drugs were administered 1 h prior to ethanol (3.5 g/kg) or vehicle. Treatment with atropine prior to vehicle or ethanol produced a statistically significant decrease in PS, whereas pilocarpine had no effect on minutes of PS. Although the mechanism by which ethanol induces PS suppression is not fully understood, these data suggest that the cholinergic system is not the only system involved in this interaction.

Ptychodiscus brevis toxin decreases the spontaneous activity of rat right atria involving muscarinic receptors and potassium channels.

Marine dinoflagellate Ptychodiscus brevis toxin (PbTx), is known to produce toxic effects on cardiovascular system. The present experiments were conducted to evaluate the effect of synthetic phosphorus containing Ptychodiscus brevis toxin on spontaneously beating right atrium in vitro. The PbTx (0.84-84 microM) decreased the rate and force of right atrial contractions in a concentration-dependent manner. Ethanol, a vehicle present in highest concentration of PbTx, had no effect on atrial rate or force of contraction. Pretreatment with atropine blocked the PbTx-induced decrease in atrial rate and force of contraction. The tetraethylammonium, a potassium channel blocker, blocked the PbTx-induced decrease in atrial rate and force, where as, L-type of calcium channel blocker, nifedipine blocked the PbTx-induced force of contraction but not the rate changes. The results indicate that the PbTx decreased the atrial rate and force of contraction via cholinergic receptors involving K+ channel.

Bradycardia induced by Mesobuthus tamulus scorpion venom involves muscarinic receptor-G-protein-coupled cell signaling pathways.

Indian red scorpion (Mesobuthus tamulus; MBT) envenomation produces various cardio-respiratory abnormalities including cardiac dysrhythmias. The underlying cell signaling pathways for the cardiac dysrhythmias produced by MBT venom are not known. The present study was therefore conducted to delineate the second messenger signaling pathways involved in MBT venom-induced atrial rhythm changes. The effects of venom and various antagonists were examined on spontaneously beating rat right atrial preparations in vitro. The MBT-venom produced an increase (35%), a decrease (45%) and again an increase (50%) in rate at 0.03, 0.3 and 3.0 microg/ml of venom, respectively. On the other hand, force of contraction exhibited a concentration-dependent rise (up to 40%) at all concentrations of venom. Pretreatment with atropine (0.3 microM) blocked the decrease in atrial rate at 0.3 microg/ml concentration of venom while no such blockade was seen in force of contraction. Submaximal concentration of ACh (0.1 nM) decreased the atrial rate by 25%. In the presence of MBT venom (0.3 microg/ml), ACh-induced fall in atrial rate was enhanced. The venom-induced fall in atrial rate and augmentation of ACh response were blocked by pertussis toxin (PTx; a Gi-inhibitor) or methylene blue (a G-cyclase inhibitor). The results indicate that the decrease in atrial rate produced by venom is mediated muscarinic by receptors via Gi-guanylyl cyclase mediated cell signaling pathways.

Intoxicación por amitraz: reporte de dos caso / Amitraz poisonig: report of two case

El incremento en la disponibilidad y uso de amitraz para el control de garrapatas en animales domésticos puede causar intoxicaciones accidentales en niños, con depresión severa del sistema nervioso central. Es necesario conocer el manejo correcto de esta intoxicación emergente. Reportamos los primeros casos de intoxicación aguda por amitraz en el estado Lara, en dos niñas quienes presentaron miosis pupilar y depresión del estado de conciencia. Una de ellas recibió varias dosis de atropina por los signos colinérgico similares, sin respuesta; posteriormente mejoró con el tratamiento de sostén. A la otra paciente se le administró precozmente naloxoma, observándose respuesta satisfactoria inmediata.

Increase of availability and use of amitraz for tick control in domestic animal, may cause accidental poisoning in children with severe CNS depression. It is necessary to know the right management of this emerging poisoning. We report the first cases of acute amitraz poisoning in Lara state, in two children who developed pupilar myosis and nervous central system depression. One of them received several doses of atropine for cholinergic-like signs, without response, but finally she improved with support therapy; to the other patient naloxona was administered early, being observed immediate satisfactory response.

Effect of KATP channel openers on myogenic and neurogenic responses in goat urinary bladder.

Isolated goat detrusor muscle exhibited spontaneous contractility with an irregular amplitude and frequency. The spontaneity of detrusor muscle exhibited a mean amplitude as 11.99 +/- 0.83 mm and frequency as 1.37 +/- 0.16/min. KATP-channel openers namely, cromakalim or pinacidil (10(-7) - 10(-4) M) added cumulatively, elicited a concentration-related inhibition of both amplitude and rate of spontaneous contractions. The mean IC50 values for both amplitude and frequency for cromakalim were 3.3 x 10(-6) M and 2.9 x 10(-6) M, respectively; and for pinacidil were 2.0 x 10(-5) M and 1.5 x 10(-5) M, respectively. Glibenclamide, a KATP-channel blocker inhibited the cromakalim-induced concentration-related relaxation of spontaneous contractions with a significant increase in its mean IC50. ACh-induced concentration-related contractile response was inhibited in the presence of either cromakalim (10(-4) M) or pinacidil (10(-4) M). The mean EC50 value of ACh, in the presence of cromakalim (2.5 x 10(-3) M) was significantly increased as compared to the control (1.2 x 10(-6) M). In the presence of glibenclamide (10(-5) M) the inhibitory effect of cromakalim was significantly reduced with consequent decrease in the EC50 value (1.9 x 10(-5) M). Application of EFS (30 V and 5 ms) on goat urinary bladder strips at 1, 2, 5, 10, 20 and 30 Hz elicited frequency-related contractile responses. Both cromakalim and pinacidil caused a rightward shift in the frequency-related contractile response curve with significant increase in the mean EF25 and EF50 values, respectively. In the presence of glibenclamide (10(-4) M), the frequency-related inhibitory response curve was shifted to left with significant (P < 0.001) increase in the mean EF25, EF50 and EF75. The present results suggest that in the goat detrusor muscle, agonist and EFS-induced contractile responses were more potently inhibited by cromakalim than pinacidil with activation of glibenclamide sensitive KATP channels.

[ effect of Atropine, Hyoscine and Promethazine on the duration of labour stages and rate of labour progress in multiparous women]

In most cases, labour is accompanied with pain. Thus, decreasing labour pain is viewed as an important duty of midwives. In this regard, decreasing the duration of labour can be of value. Customarily midwives use drugs to shorten the duration of labour, but the effectiveness of some of the drugs has not been studied systematically. Among such widely used drugs are Atropine, Hyoscine and Promethazine. In this interventional research, the effects of these drugs on labour duration were studied. 160 multiparous women in active phase of labour were selected. 120 of the above women had been administered only one of the above-mentioned drugs and no drug had been administered to the remaining 40. According to the type of drug administered, the women formed three groups, with the women with no drugs administered making the fourth groups. The four groups did not have any statistically significant difference with regard to variables such as age, occupation, education, infant sex, gestational age, infant birth weight, parity, fetal head position, and cervical dilatation at the beginning of our observation. The main result was that, the mean rate of cervical effacement [P<0.05] and descent of fetal head was not significantly different in the 4 groups. But the mean rate of cervical dilatation [P<0.05] was significantly different in four groups. In women who had been given these drugs, the mean rate of cervical dilatation was lower than the women who had not been given any drugs. The mean duration of the first stage of labour was significantly different in four groups [P<0.05]. With regard to the mean duration of the first stage of labour, it was also longer in women who had been given these drugs. The mean rate of second stage of labour and third stage of labour was not significantly different in 4 groups. The use of these drugs can reduce the rate of labour progress and increase the risk of complications, it may also be a waste of prescribed drugs

Revisión de los medicamentos antivertiginosos / a review of antivertigo medication

Objetivo. Valorar la información existente sobre los efectos de las sustancias antivertiginosas, basados en la bibliografía asequible. Información. Se localizaron artículos pertinentes en Medline y en revistas obtenidas en la ciudad de México. Selección del material. Los artículos se seleccionaron en base a su aparente consistencia interna y su relación con el propósito de la revisión. Conclusión. Se evaluaron 22 substancias pertenecientes a 8 grupos farmacológicos (colinérgicos, antihistamínicos, GABAérgicos, bloqueadores de canales de calcio, serotoninérgicos, hemorreológicos, antiagregantes plaquetarios y diuréticos) útiles en diversos padecimientos vertiginosos. Se advirtió la necesidad de un método objetivo y cuantitativo para valorar resultados de ensayos clínicos en humanos. Mientra esto no ocurra, tendremos que usar los medicamentos en base de una información veraz, confiable y basada sólidamente en la farmacología estudiada en experimentos con animales y en la valoración cuidadosa de los efectos -buenos y malos- observados en nuestros pacientes.

Influence of intragastric perfusion of aqueous spice extracts on acid secretion in anesthetized albino rats.

BACKGROUND: The effect of spices on gastric acid secretion is variable. Their mechanism of action is also not well established. AIM: To study the effect of spices on gastric acid secretion in anesthetized rats. METHODS: Aqueous extracts (10% w/v) of red pepper (Capsicum annuum), fennel (Foeniculum vulgare), omum/ajwan (Carum copticum), cardamom (Elettaria cardamomum), black pepper (Piper nigrum), cumin (Cuminum cyminum) and coriander (Coriandrum sativum) were prepared. The stomach of pentobarbitone-anesthetized rats was perfused at 0.15 mL/min with aqueous extracts of spice or acetylcholine (1 microgram/mL or 10 micrograms/mL solutions, in 40 min blocks, twice in each experiment bracketed by saline perfusions. The acid content in the samples was estimated by titration with 0.1N NaOH with phenolphthalein as indicator. Atropine 1 microgram/mL was added to the perfusion fluid in 28 experiments. In 32, acute gastric mucosal injury was induced by leaving aspirin 125 mg/Kg in the stomach for 2 h before perfusion. RESULTS: All the spices tested increased acid secretion in the following declining order: red pepper, fennel, omum, cardamom, black pepper, cumin, coriander. Red pepper increased acid secretion (mean [SEM] 0.93 [0.16] mL 0.1N HCl) to about 7 times the basal secretion (0.14 [0.05]; p < 0.005). The increase in acid secretion by the other spices was as follows: fennel 0.42 (0.11) mL 0.1 N HCl from basal secretion (0.12 [0.03]) (p < 0.02); omum 0.33 (0.05) from 0.09 (0.02) (p < 0.01); cardamom 0.28 (0.04) from 0.10 (0.03) (p < 0.005); black pepper 0.19 (0.03) from 0.04 (0.01) (p < 0.005); cumin 0.12 (0.02) from 0.08 (0.01) (p < 0.05); coriander 0.18 (0.03) from 0.09 (0.02) (p < 0.005). Atropine abolished the acid secretion induced by acetylcholine and significantly reduced acid induction by red pepper, omum and coriander, but not that by fennel. In experiments with aspirin-induced mucosal injury the basal acid secretion was low; acid secretion by red pepper and fennel was reduced significantly, but not that by acetylcholine. Cumin and coriander increased acid secretion in injured stomachs. CONCLUSION: The spices tested increased gastric acid secretion, in some by a cholinergic mechanism but by other mechanism(s) as well. Red pepper produced maximum increase in acid secretion, but this was significantly reduced in injured stomachs. Cumin and coriander increased gastric secretion in injured stomachs.