Importancia del mapeo óptico de cultivos de cardiomiocitos HL-1 en estudios electrofisiológicos / Importance of the optical mapping of HL-1 cardiomyocyte cultures in electrophysiological studies

Introducción: El desarrollo de herramientas para investigar la actividad electrofisiológica cardiaca ha permitido profundizar en el conocimiento sobre los mecanismos subyacentes a las arritmias cardiacas. Los sistemas de mapeo óptico constituyen una tecnología que responde a la necesidad de superar varios obstáculos en la experimentación. Objetivo: Proporcionar una visión general de la importancia del mapeo óptico en cultivos celulares HL-1, en las investigaciones en electrofisiología cardiaca. Métodos: Se realizó una revisión sobre los estudios electrofisiológicos que involucran la línea celular HL-1 utilizando la técnica de mapeo óptico. Conclusiones: Los trabajos se caracterizan por la implementación de la técnica respecto a la tecnología de los equipos de mapeo, a la utilización de diferentes colorantes y al objetivo de la investigación. Están enfocados en el estudio de mecanismos arritmogénicos, procesos de estiramiento mecánico o remodelación del tejido y en el análisis de nuevos biomateriales. Lo anterior, sustenta la relevancia del mapeo óptico en la investigación cardiaca(AU)

Introduction: The development of tools to study cardiac electrophysiological activity has made it possible to broaden knowledge about the mechanisms underlying cardiac arrhythmias. Optical mapping systems constitute a technology that responds to the need to overcome several hurdles in experimentation. Objective: Provide an overview of the importance of optical mapping in HL-1 cell cultures in cardiac electrophysiology research. Methods: A review was conducted of electrophysiological studies involving the HL-1 cell line using the optical mapping technique. Conclusions: The studies are characterized by implementation of the technique with respect to the technology of mapping equipment, the use of different colorants and the purpose of the research. They focus on the study of arrhythmogenic mechanisms, mechanical stretch processes or tissue remodeling as well as the analysis of new biomaterials. The above substantiates the relevance of optical mapping in cardiac research(AU)

Voltage sensitive optical mapping used to observe effects of late Na and rapidly activating delayed rectifier K currents on the right and left ventricular electrophysiological heterogeneity / 西安交通大学学报(医学版)

ABSTRACT:Objective To observe the effects of late Na current (INa‐L ) and rapidly activating delayed rectifier K current (IKr ) on ventricular heterogeneity and frequency dependency by using high resolution voltage sensitive optical mapping technology .Methods The model of 12 isolated hearts was constructed in rabbits . Voltage sensitive dye Di‐4‐ANEPPS were perfused into the isolated hearts by Langendorff method .LED source with the wave length of 532 nm was used to record APD80 and APD50 of the left and right ventricles .Experimental groups were divided into 3 groups by perfusion drugs dofetillide (30 nmol/L) ,dofetillide+ATX‐Ⅱ(1 nmol/L) ,and dofetillide +ATX‐Ⅱ +mexiletine (10μmol/L) .The subjects were intervened by the above drugs in order ,and they were self‐compared before dosing .After each drug administration ,the hearts were stimulated respectively with the BCL of 2 000 ms ,1 000 ms ,500 ms ,and 300 ms .Then we observed the changes of APD80 and APD50 in the left and right ventricles before and after the interventions .Results ① In the control group ,APD80 and APD50 of the right ventricle were longer than those of the left ventricle in response to different stimulation , and the differences increased with the decrease of stimulating frequency .② When BCL was 1000 ms ,APD80 and APD50 of the left and right ventricles were prolonged respectively after administration of dofetillide , but the differences in APD80 and APD50 were insignificant between the left and right ventricles (P>0 .05) .ΔAPD80 of the two ventricles increased significantly with the decrease of stimulating frequency . ③ After administration of ATX‐Ⅱ , when BCL was 1000 ms ,APD80 and APD50 of the left and right ventricles increased significantly compared with those in the control group and dofetillide intervention group (P0 .05) .The increase of ΔAPD80 of the two ventricles became milder when the stimulating frequency decreased . Conclusion ① IKr blocked by dofetillide did not affect the heterogeneity between the two ventricles , which showed reverse‐frequency dependence . ② In the context of blocking IKr , ATX‐Ⅱ increased the heterogeneity between the left and right ventricles and enhanced the reverse‐frequency dependence .In contrast ,mexiletine ,the blocker of INa‐L ,decreased the heterogeneity between the two ventricles and reverse‐frequency dependence .

Role of the Alternans of Action Potential Duration and Aconitine-Induced Arrhythmias in Isolated Rabbit Hearts

Under conditions of Na+ channel hyperactivation with aconitine, the changes in action potential duration (APD) and the restitution characteristics have not been well defined in the context of aconitine-induced arrhythmogenesis. Optical mapping of voltage using RH237 was performed with eight extracted rabbit hearts that were perfused using the Langendorff system. The characteristics of APD restitution were assessed using the steady-state pacing protocol at baseline and 0.1 microM aconitine concentration. In addition, pseudo-ECG was analyzed at baseline, and with 0.1 and 1.0 microM of aconitine infusion respectively. Triggered activity was not shown in dose of 0.1 microM aconitine but overtly presented in 1.0 microM of aconitine. The slopes of the dynamic APD restitution curves were significantly steeper with 0.1 microM of aconitine than at baseline. With aconitine administration, the cycle length of initiation of APD alternans was significantly longer than at baseline (287.5 +/- 9.6 vs 247.5 +/- 15.0 msec, P = 0.016). The functional reentry following regional conduction block appears with the progression of APD alternans. Ventricular fibrillation is induced reproducibly at pacing cycle length showing a 2:1 conduction block. Low-dose aconitine produces arrhythmogenesis at an increasing restitution slope with APD alternans as well as regional conduction block that proceeds to functional reentry.

Bone Marrow Mononuclear Stem Cells Transplanted in Rat Infarct Myocardium Improved the Electrical Conduction without Evidence of Proarrhythmic Effects

PURPOSE: The arrhythmogenic effect of stem cells transplantation (SCT) in an infarct myocardium is still unknown. We investigated arrhythmogenicity of SCT in rat cryo-infarct model. MATERIALS AND METHODS: In rat cryo-infarct model, bone marrow mononuclear stem cells (MNSC, 1 x 10(7) cells) were transplanted into the infarct border zone (BZ) of the LV epicardium. We compared the optical mapping and inducibility of ventricular tachycardia/fibrillation (VT/VF) among normal (n=5), cryo-infarct (n=6), and SCT rats (n=6). RESULTS: The VT/VF inducibility was higher in the cryo- infarct (47.2%, p=0.001) and SCT groups (34.6%, p=0.01) than in the normal group (12.8%). The induced VT/VF episodes persisted for more than 2 minutes in 4.3%, 26.4% and 17.3% in the normal, cryo-infarct and SCT group, respectively. In the SCT group, the action potential duration at 70% was shorter at the SCT site than the BZ during SR (75.2 +/- 8.1 vs. 145.6 +/- 4.4 ms, p=0.001) and VT (78.2 +/- 13.0 vs. 125.7 +/- 21.0 ms, p= 0.001). Conduction block was observed at the SCT site and BZ during VT. However, no reentry or ectopic foci were observed around the SCT sites. CONCLUSION: The electrical conduction was improved by SCT without evidence of augmentation of arrhythmia in the rat cryo-infarct model.

The Effects of Obstacles on the Dynamics of Ventricular Fibrillation

BACKGROUND AND OBJECTIVES: The effects of artificial obstacles on the dynamics of ventricular fibrillation have been extensively investigated with an electrical mapping system. This study was performed to assess the influence of transmural obstacles on the dynamics of wavefronts, and determine whether these can convert ventricular fibrillation to ventricular tachycardia by stabilizing the wavefronts in the fibrillating right ventricular tissues of pigs, using an optical mapping system. MATERIALS AND METHODS: The right ventricles of pigs (n=15) were excised and placed in a tissue perfusion system, with the epicardium facing up. Holes, with increasing sizes, from 2 to 8 mm in diameter, were created using a skin biopsy punch. Another 8 mm sized hole was then made adjacent to the first, and the changes in the wavefront dynamics and cycle length of the optical action potential waves investigated. RESULTS: In 14 of the 20 obstacles, in ten tissues, transient attachment of electrical activities along the rim of obstacles and transient rotation of the wavefronts were observed. During baseline ventricular fibrillation, the fibrillation cycle length was 118.5+/-24.7 msec, which was increased to 135.4+/-30.2 msec after creation of the first hole, and to 159.4+/-47.7 msec after the second (p=0.01). There was a positive correlation between the obstacle size and cycle length (r=0.43, p=0.007). In three tissues, conversion to ventricular tachycardia from ventricular fibrillation was observed after creation of the two holes. CONCLUSION: Obstacles of an appropriate size had anti-fibrillatory effects in tissues with ventricular fibrillation, which was partly explained by the temporary attachment of wavefronts to the obstacles.