Atypical Antiadrenergic Effect of Refralon as a Mechanism of High Antiarrhythmic Effectiveness.

We studied the effect of Refralon on the electrophysiological properties of the supraventricular myocardium against the background of adrenergic (epinephrine) influence in the zone of the pulmonary veins, the area where 50-90% of atrial arrhythmias is triggered. The experiments were carried out on isolated tissue preparations of Wistar rats. The multichannel microelectrode array technique was used to record action potentials simultaneously in the atrium and in the ostium and distal parts of the pulmonary veins. Epinephrine application (12-50 nM) led to depolarization of the resting potential and the conduction block in the distal part of the pulmonary veins. Refralon (30 µg/kg) restored the resting potential in the distal part of the pulmonary veins. Against the background of epinephrine, Refralon did not significantly change the duration of the action potential at 90% repolarization in comparison with control. At the same time, the comparison drug E-4031 against the background of epinephrine significantly increased the duration of action potential in the atrium and in the ostium of the pulmonary veins, and sotalol increased it only in the ostium. Neither E-4031, nor sotalol restored conduction in their distal part. Refralon has a biphasic effect under conditions of adrenergic stimulation: the fast component is responsible for stabilizing the resting potential in the pulmonary vein and reduces the dispersion of action potential duration in the atrium and pulmonary vein and is also quickly washed away, and the slow component is responsible for the increase of the action potential duration and is slowly washed away.

Suprastin (Chloropyramine) Causes Proarrhythmic Deterioration of Excitation Conduction, Depolarization and Potentiates Adrenergic Automaticity in the Pulmonary Veins Myocardium.

A number of pharmacological drugs have side effects that contribute to the occurrence of atrial fibrillation, the most common type of cardiac rhythm disorders. The clinical use of antihistamines is widespread; however, information regarding their anti- and/or proarrhythmic effects is contradictory. In this work, we studied the effects and mechanisms of the potential proarrhythmic action of the first-generation antihistamine chloropyramine (Suprastin) in the atrial myocardium and pulmonary vein (PV) myocardial tissue. In PV, chloropyramine caused depolarization of the resting potential and led to reduction of excitation wave conduction. These effects are likely due to suppression of the inward rectifier potassium current (IK1). In presence of epinephrine, chloropyramine induced spontaneous automaticity in the PV and could not be suppressed by atrial pacing. Chloropyramine change functional characteristics of PV and contribute to occurrence of atrial fibrillation. It should be noted that chloropyramine does not provoke atrial tachyarrhythmias, but create conditions for their occurrence during physical exercise and sympathetic stimulation.

Deferoxamine Improves Alveolar and Pulmonary Vascular Development by Upregulating Hypoxia-inducible Factor-1alpha in a Rat Model of Bronchopulmonary Dysplasia

Fetal lung development normally occurs in a hypoxic environment. Hypoxia-inducible factor (HIF)-1alpha is robustly induced under hypoxia and transactivates many genes that are essential for fetal development. Most preterm infants are prematurely exposed to hyperoxia, which can halt hypoxia-driven lung maturation. We were to investigate whether the HIF-1alpha inducer, deferoxamine (DFX) can improve alveolarization in a rat model of bronchopulmonary dysplasia (BPD). A rat model of BPD was produced by intra-amniotic lipopolysaccharide (LPS) administration and postnatal hyperoxia (85% for 7 days), and DFX (150 mg/kg/d) or vehicle was administered to rat pups intraperitoneally for 14 days. On day 14, the rat pups were sacrificed and their lungs were removed and examined. A parallel in vitro study was performed with a human small airway epithelial cell line to test whether DFX induces the expression of HIF-1alpha and its target genes. Alveolarization and pulmonary vascular development were impaired in rats with BPD. However, DFX significantly ameliorated these effects. Immunohistochemical analysis showed that HIF-1alpha was significantly upregulated in the lungs of BPD rats treated with DFX. DFX was also found to induce HIF-1alpha in human small airway epithelial cells and to promote the expression of HIF-1alpha target genes. Our data suggest that DFX induces and activates HIF-1alpha, thereby improving alveolarization and vascular distribution in the lungs of rats with BPD.

Esclerose endoscópica de varizes esofágicas e repercussöes pulmonares / Esophageal varices sclerotheraphy and pulmonary side effects

Alteraçöes respiratórias já foram descritas após escleroterapia endoscópica de varizes esofágicas. O oleato de etanolamina, agente esclerosante gorduroso, atingindo a circulaçäo sistêmica, possibilita o desenvolvimento de lesäo de vasos pulmonares nos pacientes submetidos a escleroterapia. Foram estudados 17 pacientes (grupo I) com hipertensäo portal e varizes esofágicas, sendo 13 com diagnóstico compatível com esquistossomose e quatro com doença crónica parenquimatosa do fígado. O grupo controle constou de dez pacientes (grupo II) com hipertensäo portal e varizes esofágicas, sendo oito com diagnóstico compatível com esquistossomose e dois com doença crónica parenquimatosa do fígado. O grupo I submeteu-se a escleroterapia com oleato de etanolamina pela técnica intravasal, enquanto no grupo controle (grupo II) foi feito procedimento endoscópico idêntico, sem o tratamento escleroterápico. Os dois grupos (I e II) foram submetidos, previamente e durante o estudo, a radiografia de tórax, espirometria, gasometria arterial e cintilografia pulmonar de inalaçäo e perfusäo. No grupo I, a média da pressäo parcial de oxigênio no sangue arterial (pO2) antes da escleroterapia foi de 81,8mmHg, reduzindo-se para 78,9mmHg duas horas após e tornando-se significativamente baixa quatro e oito horas após, 73,8mmHg (p < 0,05) e 70,1mmHg (p < 0,05), respectivamente. Com 24 horas, a pO2 estava em 77,03mmHg. Neste grupo, um paciente desenvolveu embolia pulmonar. Nos pacientes do grupo controle, a pO2 antes da endoscopia foi de 82,7mmHg, reduzindo-se para 68,9mmHg duas horas após (p < 0,05), para 67,6mmHg quatro horas após (p < 0,05), para 71,8mmHg oito horas após (p < 0,05) e para 75,2mmHg 24 horas após. Nossos resultados sugerem que o procedimento da endoscopia digestiva alta sob sedaçäo produz hipoxemia arterial e que talvez a escleroterapia com oleato de etanolamina pela técnica intravasal pode causar embolia pulmonar.