218 research outputs found
Animals in cardiovascular research: important role of rabbit models in cardiac electrophysiology
Different effects of amiodarone and dofetilide on the dispersion of repolarization between well-coupled ventricular and purkinje fibers
Increased transmural dispersion of repolarization is an established contributing factor to ventricular tachyar-rhythmias. In this study, we evaluated the effect of chronic amiodarone treatment and acute administration of dofetilide in canine cardiac preparations containing electrotonically coupled Purkinje fibers (PFs) and ventricular muscle (VM) and compared the effects to those in uncoupled PF and VM preparations using the conventional microelectrode technique. Dispersion between PFs and VM was inferred from the difference in the respective action potential durations (APDs). In coupled preparations, amiodarone decreased the difference in APDs between PFs and VM, thus decreasing dispersion. In the same preparations, dofetilide increased the dispersion by causing a more pronounced prolongation in PFs. This prolongation was even more emphasized in uncoupled PF preparations, while the effect in VM was the same. In uncoupled preparations, amiodarone elicited no change on the difference in APDs. In conclusion, amiodarone decreased the dispersion between PFs and VM, while dofetilide increased it. The measured difference in APD between cardiac regions may be the affected by electrotonic coupling; thus, studying PFs and VM separately may lead to an over-or underestimation of dispersion. © 2021, Canadian Science Publishing. All rights reserved
Possible mechanisms of sudden cardiac death in top athletes: a basic cardiac electrophysiological point of view
A QT-intervallum rövidtávú variabilitásának fokozódása előre jelzi a ciszaprid indukálta kamrai ritmuszavarok kialakulását [Increased short-term variability of the QT interval predicts cisapride induced ventricular arrhythmias]
Resveratrol and derivatives for the treatment of atrial fibrillation
Resveratrol is a bioactive polyphenol, found in grapes, red wine, and peanuts, and has recently garnered much media and scientific attention for its diverse beneficial health effects as a nutritional supplement or nutraceutical. Of particular interest are the well-documented cardioprotective effects of resveratrol that are mediated by diverse mechanisms, including its antioxidant and vascular effects. However, it is now becoming clear that resveratrol may also exhibit direct effects on cardiac function and rhythm through modulation of signaling pathways that regulate cardiac remodeling and ion channel activity that controls cardiac excitability. Resveratrol may therefore possess antiarrhythmic properties that contribute to the cardiovascular benefits of resveratrol. Atrial fibrillation (AF) is the most common cardiac arrhythmia, although current therapies are suboptimal. Our laboratory has been studying resveratrol's effects on cardiac ion channels and remodeling pathways, and we initiated a drug development program aimed at generating novel resveratrol derivatives with improved efficacy against AF when compared to currently available therapeutics. This review therefore focuses on the effects of resveratrol and new derivatives on a variety of cardiac ion channels and molecular pathways that contribute to the development and maintenance of atrial fibrillation
The hidden electrophysiological cardiotoxic effects of rofecoxib on rabbit ventricular preparations : [abstract]
Proaritmiás gyógyszermellékhatások vizsgálata transzgenikus hosszú QT-szindrómás nyúlmodellek segítségével
A gyógyszer okozta ritmuszavar a különböző vegyületek súlyos és potenciálisan halálos mellékhatása. A proaritmiás mellékhatást gyakran az adott gyógyszernek a szívizom-repolarizáló ionáramait gátló hatásaival hozzák összefüggésbe, ami az EKG-n a QT-intervallum meghosszabbodásához vezet. A gyógyszerfejlesztésben alkalmazott kifinomult szűrési módszerek ellenére a proaritmia megbízható előrejelzése továbbra is jelentős kihívást jelent. Bár a gyógyszerek által kiváltott QT-idő megnyúlással összefüggő proaritmiás hatás iránt fokozottan érzékenyítenek a betegek repolarizációs tartalékát csökkentő kórfolyamatok, a legtöbb gyógyszerbiztonsági szűrésre használt modellrendszer normális, egészséges sejteket, szöveteket és állatokat használ fel. A közelmúltban több, csökkent repolarizációs tartalékkal rendelkező transzgenikus hosszú QT-szindrómás (LQTS) nyúlmodellt hoztak létre. Összefoglaló közleményünkben e modellek lehetséges felhasználását tárgyaljuk a gyógyszerindukált aritmiák előrejelzésére, összefüggésben a különböző modellekben tapasztalt repolarizáló szívizom ionáram-károsodással. Emellett áttekintjük a rendelkezésre álló transzgenikus LQTS-nyúlmodellek elektrofiziológiai jellemzőit, a modelleken végzett farmakológiai elvi bizonyító vizsgálatokat, kiemelve a transzgenikus nyúl LQTS-modellek előnyeit és hátrányait a gyógyszerindukálta ritmuszavar kutatásában
Coxsackie and adenovirus receptor is a modifier of cardiac conduction and arrhythmia vulnerability in the setting of myocardial ischemia.
OBJECTIVES: The aim of this study was to investigate the modulatory effect of the coxsackie and adenovirus receptor (CAR) on ventricular conduction and arrhythmia vulnerability in the setting of myocardial ischemia. BACKGROUND: A heritable component in the risk of ventricular fibrillation during myocardial infarction has been well established. A recent genome-wide association study of ventricular fibrillation during acute myocardial infarction led to the identification of a locus on chromosome 21q21 (rs2824292) in the vicinity of the CXADR gene. CXADR encodes the CAR, a cell adhesion molecule predominantly located at the intercalated disks of the cardiomyocyte. METHODS: The correlation between CAR transcript levels and rs2824292 genotype was investigated in human left ventricular samples. Electrophysiological studies and molecular analyses were performed using CAR haploinsufficient (CAR(+/-)) mice. RESULTS: In human left ventricular samples, the risk allele at the chr21q21 genome-wide association study locus was associated with lower CXADR messenger ribonucleic acid levels, suggesting that decreased cardiac levels of CAR predispose to ischemia-induced ventricular fibrillation. Hearts from CAR(+/-) mice displayed slowing of ventricular conduction in addition to an earlier onset of ventricular arrhythmias during the early phase of acute myocardial ischemia after ligation of the left anterior descending artery. Expression and distribution of connexin 43 were unaffected, but CAR(+/-) hearts displayed increased arrhythmia susceptibility on pharmacological electrical uncoupling. Patch-clamp analysis of isolated CAR(+/-) myocytes showed reduced sodium current magnitude specifically at the intercalated disk. Moreover, CAR coprecipitated with NaV1.5 in vitro, suggesting that CAR affects sodium channel function through a physical interaction with NaV1.5. CONCLUSIONS: CAR is a novel modifier of ventricular conduction and arrhythmia vulnerability in the setting of myocardial ischemia. Genetic determinants of arrhythmia susceptibility (such as CAR) may constitute future targets for risk stratification of potentially lethal ventricular arrhythmias in patients with coronary artery disease
Capsaicin-Sensitive Sensory Nerves and the TRPV1 Ion Channel in Cardiac Physiology and Pathologies
Cardiovascular diseases, including coronary artery disease, ischemic heart diseases such as acute myocardial infarction and postischemic heart failure, heart failure of other etiologies, and cardiac arrhythmias, belong to the leading causes of death. Activation of capsaicin-sensitive sensory nerves by the transient receptor potential vanilloid 1 (TRPV1) capsaicin receptor and other receptors, as well as neuropeptide mediators released from them upon stimulation, play important physiological regulatory roles. Capsaicin-sensitive sensory nerves also contribute to the development and progression of some cardiac diseases, as well as to mechanisms of endogenous stress adaptation leading to cardioprotection. In this review, we summarize the role of capsaicin-sensitive afferents and the TRPV1 ion channel in physiological and pathophysiological functions of the heart based mainly on experimental results and show their diagnostic or therapeutic potentials. Although the actions of several other channels or receptors expressed on cardiac sensory afferents and the effects of TRPV1 channel activation on different non-neural cell types in the heart are not precisely known, most data suggest that stimulation of the TRPV1-expressing sensory nerves or stimulation/overexpression of TRPV1 channels have beneficial effects in cardiac diseases
- …