43 research outputs found
Amiodarone-Induced Postrepolarization Refractoriness Suppresses Induction of Ventricular Fibrillation
Effects of superoxide donor menadione in adult Rat myocardium are associated with increased diastolic intracellular calcium.
Superoxide anions have been associated with many aspects of cardiovascular disease. Menadione is a superoxide anion donor that alters the heart's electrical and mechanical functions. The aim of this study was to demonstrate simultaneous changes in intracellular Ca2+ ([Ca2+]i) and mechanical activity in intact adult cardiac myocytes, and mechanical activity and electrical activity in isolated whole hearts in order to provide greater insight into the mechanisms associated with the detrimental effects of menadione on the myocardium. Isolated hearts from adult male Wistar rats (nâ
=â
11, 200â250â
g) were Langendorff perfused at 38°C with a KrebsâHenseleit solution. A saline-filled balloon was placed in the left ventricle (LV) in order to measure diastolic and developed pressure. Monophasic action potentials were simultaneously recorded from the epicardial surface. External stimulation at 5â
Hz and intrinsic pacing were used throughout a 10â
min control period and 30â
min exposure to 50â
ÎŒM menadione. Single LV myocytes (nâ
=â
7 from nâ
=â
4 animals) were loaded with the Ca2+-indicator Fura4-AM, stimulated at 1â
Hz and exposed to 50â
ÎŒM menadione. Myocyte length was simultaneously measured with [Ca2+]i using a video edge detection system. In isolated hearts, exposure to menadione significantly decreased contractility and action potential duration (with a similar time course); intrinsic heart rate and rhythmicity. Diastolic pressure was significantly increased. In single adult myocytes, menadione caused a significant increase in diastolic [Ca2+]i and a decrease in resting cell length and led to spontaneous release of [Ca2+]i. We conclude that the effects of menadione upon electrical and mechanical activity of the heart are at least in part a consequence of dysregulation of [Ca2+]i handling and the subsequent increase in diastolic [Ca2+] alterations in [Ca2+]i are consistent with the generation of delayed after depolarization arrhythmias
Time course and extent of central and peripheral adaptations during endurance training in coronary artery bypass graft patients: Influence of training intensity
Inhibition of postischemic reperfusion arrhythmias by an SOD derivative that circulates bound to albumin with prolonged in vivo half-life
Molecular Bases of Congenital Adrenal Hyperplasia
Congenital adrenal hiperplasia (CAH) is a recessive autossomic disease caused by inherited defects in cortisol biosynthesis. The manifestations are caused both by the deficient synthesis of cortisol, and sometimes of aldosterone, and by accumulation of the precursor steroids. The objective of this review is to present the molecular mechanisms of the main enzymatic defects involved in the etiopathogenesis of CAH. Deficiency of 21-hydroxylase (21OH) accounts for more than 95% of all cases of CAH. The human genome contains two CYP genes: one active, CYP21, and a pseudogene, CYP21P. Both are highly homologous (98%), facilitating recombination events during meiosis, leading to duplication and/or deletion or conversion of these genes. Additionally, point mutations have also been described. Deficiency of 11beta-hydroxylase (11betaOH) is caused by mutations in the CYP11B1 gene, and accounts for 5% of all cases. Some mutations are recurrent, and mainly located on exons 6-8, which is considered a hot-spot area in CYP11B1 gene. Deficiency of 17alpha-hydroxylase (17OH) is caused by mutations in the CYP17 gene, producing a truncated or impaired protein. These mutations have been described in patients with combined deficiencies of 17OH and 17,20-lyase or with isolated 17,20-lyase. Finally, CAH caused by 3beta-HSD deficiency is the consequence of mutations in the gene HSD3B2 that encodes 3beta-HSD type II. In the classical form of the disease nonsense mutations, insertion and deletions have been described, while in non classical forms, mutations result in diminished enzyme affinity and loss of enzyme activity.Hiperplasia adrenal congĂȘnita (HAC) Ă© uma doença autossĂŽmica recessiva decorrente da alteração de enzimas que participam da sĂntese do cortisol. As manifestaçÔes podem ser causadas pela deficiĂȘncia do cortisol e, em alguns casos, aldosterona e pelo acĂșmulo de precursores. O objetivo desta revisĂŁo Ă© apresentar os mecanismos moleculares dos principais defeitos enzimĂĄticos envolvidos na etiopatogĂȘnese da HAC. A deficiĂȘncia da 21-hidroxilase (21OH) ocorre em 95% dos casos de HAC. Existem dois genes que codificam o P450c21: um ativo, CYP21, e um pseudogene CYP21P. Ambos sĂŁo altamente homĂłlogos (98%), o que favorece o emparelhamento desigual dos cromossomos homĂłlogos durante a meiose, levando a duplicaçÔes e/ou deleçÔes ou conversĂ”es desses genes. Adicionalmente, foram tambĂ©m descritas mutaçÔes de ponto, muitas delas presentes no pseudogene sugerindo microconversĂ”es. MutaçÔes no gene CYP11B1 causam HAC por deficiĂȘncia da 11beta-hidroxilase, forma esta que corresponde a 5% dos casos. Algumas mutaçÔes sĂŁo recorrentes, situando-se principalmente entre os exons 6-8 que representaria uma ĂĄrea hot-spot no gene CYP11B1. A deficiĂȘncia de 17-hidroxilase Ă© causada por mutaçÔes no gene CYP17, que codificam uma proteĂna alterada, levando a deficiĂȘncia total ou parcial de 17-hidroxilação e 17,20-liase ou deficiĂȘncia isolada de 17,20-liase. Finalmente, deficiĂȘncia de 3beta-HSD Ă© causada por mutaçÔes no gene HSD3B2, que codifica a enzima 3beta-HSD tipo II e estas mutaçÔes tĂȘm sido associadas tanto com a forma clĂĄssica como com a forma nĂŁo clĂĄssica da deficiĂȘncia da 3beta-HSD