effect of paroxetine on ouabain-induced toxicity in isolated guinea pig atria

It has been reported that selective serotonin reuptake inhibitors [SSRIs] possess some cardiac effects. In the present study we have investigated the effect of paroxetine [PX], a potent SSRI agent, on spontaneously as well as ouabain-induced arrhythmia beating isolated guinea-pig atria. The Guinea-pig heart was rapidly removed; the auricles were dissected out in oxygenated modified Krebs solution. The rate and force of spontaneous contractions were recorded isometrically with a photosensitive transducer. PX [1-16 micro g/ml] caused a dose-dependent decrease in the rate of contractions [14-70%] and contractile force [8-16%]. Ouabain alone [1.2 micro g/ml] produced arrhythmia at 7.2 +/- 1.5 min and asystole at 20.1 +/- 3.1 min. Pretreatment with PX [4 micro g/ml] significantly increased the time of arrhythmia onset to 19.8 min. In addition, PX prolonged the duration of action beating from 20.1 +/- 3.1 min to 43.1 +/- 2.6 and delayed the occurrence of asystole. The pattern of contractile force by PX + ouabain treatment was more regular than that observed after administration of ouabain alone. The above findings may the probably be due to the inhibition of cardiac Na[+] and Ca[2+] channels or autonomic nervous system. Results also suggest that PX may reduce the membrane conductance through inhibition of ionic channels to prevent ouabain-induced arrhythmia

Transplantation of Neural Differentiated Human Mesenchymal Stem Cells into the Cochlea of an Auditory-neuropathy Guinea Pig Model

The aim of this study was to determine the effects of transplanted neural differentiated human mesenchymal stem cells (hMSCs) in a guinea pig model of auditory neuropathy. In this study, hMSCs were pretreated with a neural-induction protocol and transplanted into the scala tympani of the guinea pig cochlea 7 days after ouabain injury. A control model was made by injection of Hanks balanced salt solution alone into the scala tympani of the guinea pig cochlea 7 days after ouabain injury. We established the auditory neuropathy guinea pig model using 1 mM ouabain application to the round window niche. After application of ouabain to the round window niche, degeneration of most spiral ganglion neurons (SGNs) without the loss of hair cells within the organ of Corti and increasing the auditory brain responses (ABR) threshold were found. After transplantation of neural differentiated hMSCs, the number of SGNs was increased, and some of the SGNs expressed immunoreactivity with human nuclear antibody under confocal laser scanning microscopy. ABR results showed mild hearing recovery after transplantation. Based on an auditory neuropathy animal model, these findings suggest that it may be possible to replace degenerated SGNs by grafting stem cells into the scala tympani.

Altered levels of nodal excitability by rate-dependent inhibitory effects of essential oil of Citrus aurantium on the electrophysiological properties of isolated perfused rabbit AV-Node: protective role in the prevention of ouabain toxicity / Alteración de los niveles de excitabilidad nodal por efectos inhibitorios velocidad-dependiente del aceite esencial de Citrus aurantium sobre las propiedades electrofisiológicas del nodo AV Aislado y perfundido de conejo: papel protector en la prevención de toxicidad por ouabaína

Treatment of supraventricular arrhythmia includes a wide range of medical interventions. Herbal remedies are suitable alternatives to synthetic drugs due to their availability, minimal side effects and lower price. Pharmacological studies and traditional medical literature point to the cardiovascular effects of Citrus aurantium L. (Rutaceae) in many instances. In the present study we used isolated perfused AV-node of rabbit as an experimental model to determine the effect of various concentrations of essential oil of C. aurantium (0.1-0.3 v/v) on the nodal conduction time and refractoriness of an isolated rabbit AV-nodal preparations. Selective stimulation protocols were used to independently quantify AV nodal recovery, facilitation and fatigue in 18 rabbits. Our results showed concentration-dependent and rate-independent suppressive effects of essence of C. aurantium on the Wenchebach cycle length (WBCL), AV Conduction Time (AVCT) and effective and functional refractory periods (ERP & FRP). Functional properties such as facilitation and fatigue were significantly increased by this plant. Citrus aurantium plays a protective role against the toxic effects of ouabaine by increasing AV nodal conduction time and refractoriness. The above results indicated differential effects of C. aurantium on slow and fast pathways, with a dominant role on fast pathways. This research has explained the protective role of C. aurantium on ouabaine toxicity. All results indicated the potential anti-arrhythmic effects of C. aurantium in treating supraventricular tachyarrhythmia.

El tratamiento de la arritmia supraventricular incluye una amplia gama de intervenciones médicas. Los remedios herbarios son alternativas adecuadas a las drogas sintéticas debido a su disponibilidad, con escasos efectos secundarios y bajo precio. Estudios farmacológicos y la literatura médica tradicional señalan los efectos cardiovasculares de Citrus aurantium L. (Rutaceae) en muchos casos. En el presente estudio se usaron aislados perfundidos del nodo AV de conejo como modelo experimental para determinar el efecto de diferentes concentraciones de aceite esencial de C. aurantium (0,1-0,3 v/v) sobre en el tiempo de conducción nodal y refractariedad. Un protocolo de estimulación selectiva se utilizó para cuantificar de forma independiente la recuperación, la facilitación y la fatiga del nodo AV en 18 conejos. Nuestros resultados muestran efectos supresores dependientes de la concentración e independiente de la velocidad de la esencia de C. aurantium sobre la duración del ciclo Wenchebach (WBCL), tiempo de conducción AV (AVTC) y períodos refractarios eficaz y funcional (PRE y PRF). Propiedades funcionales tales como la facilitación y la fatiga se incrementaron de manera significativa por esta planta. La Citrus aurantium juega un papel protector contra los efectos tóxicos de ouabaína al incrementar el tiempo de conducción AV nodal y la refractariedad. Los resultados indican efectos diferenciales de C. aurantium sobre las vías lentas y rápidas, con un papel dominante en las vías rápidas. Esta investigación ha explicado el papel protector de C. aurantium sobre la toxicidad ouabaine. Todos los resultados indican los posibles efectos anti-arrítmicos de C. aurantium en el tratamiento de taquiarritmias supraventriculares.

Effect of B-HT 920 on cardiotoxic effects of ouabain in guinea pigs.

Effect of B-HT 920, a selective alpha 2 adrenoceptor agonist, was studied on ouabain induced cardiac arrhythmias and cardiac arrest in guinea pigs. Ventricular premature beats, ventricular tachyarrhythmias and cardiac arrest were induced in anaesthetized guinea pigs by slow infusion of ouabain. B-HT 920 accorded significant protection to guinea pigs against ouabain induced arrhythmias. Yohimbine inhibited the antiarrhythmic effect of B-HT 920 significantly. It is concluded that the protective effect of B-HT 920 against ouabain induced cardiac arrhythmias and cardiac arrest is mediated through the stimulation of alpha 2 adrenoceptors.