Day 2 :
Israel Institute of Technology, Israel
Keynote: Molecular characterization and functional properties of induced pluripotent stem cells-derived cardiomyocytes from healthy and diseased individuals. Models for investigating inherited cardiac diseases
Time : 09:05-09:55
Ofer Binah works at the Technion – Israel Institute of Technology, Israel. He is a Professor in the Department of Physiology, Biophysics and Systems Biology at the Ruth and Bruce Rappaport Faculty of Medicine. He has published more than 108 articles in reputed journals.
In view of the therapeutic potential of cardiomyocytes derived from human induced pluripotent stem cells (iPSC-CM), our overall goal is to investigate their molecular characteristics, functional properties related to the excitation-contraction coupling (e.g., [Ca2+]i handling), pacemaker function and underlying ion currents, the effects of b-adrenergic stimulation, and responsiveness to common modifiers of cardiac function (e.g. If blocker). The iPSC clones we investigate are derived from human dermal fibroblasts or hair keratinocytes, and reprogramming is accomplished by infecting the cells with four human genes: OCT4, Sox2, Klf4 and C-Myc. Our major findings show that iPSC-CM: express cardiac specific RNA and proteins; exhibit regular pacemaker activity; exhibit key features of the excitation contraction coupling machinery; respond to ryanodine and caffeine (though less than adult cardiomyocytes), and express the SR-Ca2+ handling proteins ryanodine receptor and calsequestrin; respond to autonomic agonists and antagonists. Hence, our work demonstrates that iPSC-CM exhibit features resembling the adult myocardium, and thus constitute a potential source for cardiac regeneration. Concomitantly, in order to decipher the pathological mechanisms of inherited cardiac arrhythmias and cardiomyopathies, we are investigating iPSC-CM generated from skin biopsies/keratinocytes obtained from patient’s catecholaminergic polymorphic ventricular tachycardia (CPVT), laminopathies, WPW and Duchenne muscular dystrophy (DMD). Our research shows that the mutated iPSC-CM feature key clinical phenotype of the disease, thus establishing the foundation for developing novel drug modalities.
Nicklaus Children’s Hospital, USA
Keynote: Dexmedetomidine use in patients undergoing electrophysiological study for atrial tachyarrhythmias
Time : 09:55-10:45
Christopher F Tirotta has been an active member of Miami Children’s Hospital Medical Staff since 1991, practicing in the Department of Anesthesiology. He has served as the Director of Cardiac Anesthesia since 2002. He also works in the Department of Anesthesiology at the University of Miami. He received his BA from Cornell University in 1982 and his MD from New York University School of Medicine in 1986. He also received an MBA degree from Columbia University in 1999. He completed his Internship in Internal Medicine from Stony Brook University in 1987. He completed his Residency training in Anesthesiology from the University of Miami, Jackson Memorial Hospital in 1990. He is sub-specialized in Pediatric and Cardiovascular Anesthesia, including Heart Transplantation. He has been the Principal Investigator for a number of clinical drug/device trials.
Dexmedetomidine (DEX) is a selective alpha-2 adrenergic agonist with sedative, analgesic and anxiolytic properties. DEX has not been approved for use in pediatrics. DEX has been reported to depress sinus node and atrioventricular (AV) nodal function in pediatric patients; it was even suggested that the use of DEX may not be desirable during electrophysiological studies (EPS). Other studies have reported no association between DEX use and any significant EKG interval abnormalities in patients with congenital heart disease, other than a decrease in HR. We reviewed all cases presented to the CCL for diagnosis or treatment of atrial tachyarrhythmias since 2007. The patients were stratified into three different groups. Group 1 patients did not receive any DEX. Group 2 patients received a DEX infusion of 0.5-1 mcg/kg/hr. Group 3 patients received a DEX infusion of 0.5-1 mcg/kg/hr and a DEX bolus prior to the infusion of 0.5-1 mcg/kg. We then compared those patients for the following variables: Demographic data and anesthetic data like age, sex, height, weight; mask vs. IV induction, identity of induction agent, amount of sevoflurane and propofol used; amount of DEX used; presence of congenital heart disease and other co-morbidities; the need for isoproterenol (ISO) and dose, the need for adenosine and dose and the need for any other medications to effect rhythm both before and after RFA; the ability to induce the arrhythmia, the type of arrhythmia, the presence of Wolf-Parkinson-White (WPW) syndrome, the presence of an accessory pathway, the ablation rate and the recurrence rate. There were no differences in any of the demographic data between groups. There was no difference in the anesthetic data, except there was a lesser amount of propofol and sevoflurane used in the DEX groups. There was no difference in the electrophysiologic parameters between groups, except the Group 1 patients did require the use of ISO in the pre-ablation period less often compared to the DEX groups. However, there was no difference in the ability to induce the arrhythmia, the percentage of patients ablated, and the recurrence rate between groups.