Ectopic Pacemaker

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Audrey Baldessari - One of the best experts on this subject based on the ideXlab platform.

  • Human embryonic stem cell–derived cardiomyocytes restore function in infarcted hearts of non-human primates
    Nature Biotechnology, 2018
    Co-Authors: Billy Chen, Xiulan Yang, James A Fugate, Faith A Kalucki, Akiko Futakuchi-tsuchida, Larry Couture, Keith W Vogel, Clifford A Astley, Audrey Baldessari, Jason Ogle
    Abstract:

    Pluripotent stem cell–derived cardiomyocyte grafts can remuscularize substantial amounts of infarcted myocardium and beat in synchrony with the heart, but in some settings cause ventricular arrhythmias. It is unknown whether human cardiomyocytes can restore cardiac function in a physiologically relevant large animal model. Here we show that transplantation of ∼750 million cryopreserved human embryonic stem cell–derived cardiomyocytes (hESC-CMs) enhances cardiac function in macaque monkeys with large myocardial infarctions. One month after hESC-CM transplantation, global left ventricular ejection fraction improved 10.6 ± 0.9% vs. 2.5 ± 0.8% in controls, and by 3 months there was an additional 12.4% improvement in treated vs. a 3.5% decline in controls. Grafts averaged 11.6% of infarct size, formed electromechanical junctions with the host heart, and by 3 months contained ∼99% ventricular myocytes. A subset of animals experienced graft-associated ventricular arrhythmias, shown by electrical mapping to originate from a point-source acting as an Ectopic Pacemaker. Our data demonstrate that remuscularization of the infarcted macaque heart with human myocardium provides durable improvement in left ventricular function. Cardiomyocyte transplantation after heart attack improves contractile function in monkeys.

  • human embryonic stem cell derived cardiomyocytes restore function in infarcted hearts of non human primates
    Nature Biotechnology, 2018
    Co-Authors: Billy Chen, Xiulan Yang, James A Fugate, Faith A Kalucki, Larry Couture, Keith W Vogel, Clifford A Astley, Akiko Futakuchitsuchida, Audrey Baldessari
    Abstract:

    Cardiomyocyte transplantation after heart attack improves contractile function in monkeys. Pluripotent stem cell–derived cardiomyocyte grafts can remuscularize substantial amounts of infarcted myocardium and beat in synchrony with the heart, but in some settings cause ventricular arrhythmias. It is unknown whether human cardiomyocytes can restore cardiac function in a physiologically relevant large animal model. Here we show that transplantation of ∼750 million cryopreserved human embryonic stem cell–derived cardiomyocytes (hESC-CMs) enhances cardiac function in macaque monkeys with large myocardial infarctions. One month after hESC-CM transplantation, global left ventricular ejection fraction improved 10.6 ± 0.9% vs. 2.5 ± 0.8% in controls, and by 3 months there was an additional 12.4% improvement in treated vs. a 3.5% decline in controls. Grafts averaged 11.6% of infarct size, formed electromechanical junctions with the host heart, and by 3 months contained ∼99% ventricular myocytes. A subset of animals experienced graft-associated ventricular arrhythmias, shown by electrical mapping to originate from a point-source acting as an Ectopic Pacemaker. Our data demonstrate that remuscularization of the infarcted macaque heart with human myocardium provides durable improvement in left ventricular function.

  • human embryonic stem cell derived cardiomyocytes restore function in infarcted hearts of non human primates
    Nature Biotechnology, 2018
    Co-Authors: Yen Wen Liu, Billy Chen, Xiulan Yang, James A Fugate, Faith A Kalucki, Keith W Vogel, Clifford A Astley, Akiko Futakuchitsuchida, Larry A Couture, Audrey Baldessari
    Abstract:

    Pluripotent stem cell-derived cardiomyocyte grafts can remuscularize substantial amounts of infarcted myocardium and beat in synchrony with the heart, but in some settings cause ventricular arrhythmias. It is unknown whether human cardiomyocytes can restore cardiac function in a physiologically relevant large animal model. Here we show that transplantation of ∼750 million cryopreserved human embryonic stem cell-derived cardiomyocytes (hESC-CMs) enhances cardiac function in macaque monkeys with large myocardial infarctions. One month after hESC-CM transplantation, global left ventricular ejection fraction improved 10.6 ± 0.9% vs. 2.5 ± 0.8% in controls, and by 3 months there was an additional 12.4% improvement in treated vs. a 3.5% decline in controls. Grafts averaged 11.6% of infarct size, formed electromechanical junctions with the host heart, and by 3 months contained ∼99% ventricular myocytes. A subset of animals experienced graft-associated ventricular arrhythmias, shown by electrical mapping to originate from a point-source acting as an Ectopic Pacemaker. Our data demonstrate that remuscularization of the infarcted macaque heart with human myocardium provides durable improvement in left ventricular function.

  • Human embryonic stem cell–derived cardiomyocytes restore function in infarcted hearts of non-human primates
    Nature biotechnology, 2018
    Co-Authors: Yen Wen Liu, Billy Chen, Xiulan Yang, James A Fugate, Faith A Kalucki, Akiko Futakuchi-tsuchida, Keith W Vogel, Clifford A Astley, Larry A Couture, Audrey Baldessari
    Abstract:

    Pluripotent stem cell-derived cardiomyocyte grafts can remuscularize substantial amounts of infarcted myocardium and beat in synchrony with the heart, but in some settings cause ventricular arrhythmias. It is unknown whether human cardiomyocytes can restore cardiac function in a physiologically relevant large animal model. Here we show that transplantation of ∼750 million cryopreserved human embryonic stem cell-derived cardiomyocytes (hESC-CMs) enhances cardiac function in macaque monkeys with large myocardial infarctions. One month after hESC-CM transplantation, global left ventricular ejection fraction improved 10.6 ± 0.9% vs. 2.5 ± 0.8% in controls, and by 3 months there was an additional 12.4% improvement in treated vs. a 3.5% decline in controls. Grafts averaged 11.6% of infarct size, formed electromechanical junctions with the host heart, and by 3 months contained ∼99% ventricular myocytes. A subset of animals experienced graft-associated ventricular arrhythmias, shown by electrical mapping to originate from a point-source acting as an Ectopic Pacemaker. Our data demonstrate that remuscularization of the infarcted macaque heart with human myocardium provides durable improvement in left ventricular function.

Michel Haïssaguerre - One of the best experts on this subject based on the ideXlab platform.

  • Pseudo sinus rhythm originating from the left superior pulmonary vein in a patient with paroxysmal atrial fibrillation.
    Journal of cardiovascular electrophysiology, 2001
    Co-Authors: Teiichi Yamane, Dipen Shah, Pierre Jaïs, Michel Haïssaguerre
    Abstract:

    Pseudo Sinus Rhythm Originating from a Pulmonary Vein. We report the case of a patient with paroxysmal atrial fibrillation in whom the background cardiac rhythm falsely mimicked sinus rhythm but actually originated from the left superior pulmonary vein. P waves during the Ectopic rhythm were flat in lead I, negative in lead aVL, and without a typical “dome-and-dart” feature in precordial leads. Radiofrequency applications inside the left superior pulmonary vein eliminated both atrial fibrillation and the Ectopic Pacemaker.

Billy Chen - One of the best experts on this subject based on the ideXlab platform.

  • Human embryonic stem cell–derived cardiomyocytes restore function in infarcted hearts of non-human primates
    Nature Biotechnology, 2018
    Co-Authors: Billy Chen, Xiulan Yang, James A Fugate, Faith A Kalucki, Akiko Futakuchi-tsuchida, Larry Couture, Keith W Vogel, Clifford A Astley, Audrey Baldessari, Jason Ogle
    Abstract:

    Pluripotent stem cell–derived cardiomyocyte grafts can remuscularize substantial amounts of infarcted myocardium and beat in synchrony with the heart, but in some settings cause ventricular arrhythmias. It is unknown whether human cardiomyocytes can restore cardiac function in a physiologically relevant large animal model. Here we show that transplantation of ∼750 million cryopreserved human embryonic stem cell–derived cardiomyocytes (hESC-CMs) enhances cardiac function in macaque monkeys with large myocardial infarctions. One month after hESC-CM transplantation, global left ventricular ejection fraction improved 10.6 ± 0.9% vs. 2.5 ± 0.8% in controls, and by 3 months there was an additional 12.4% improvement in treated vs. a 3.5% decline in controls. Grafts averaged 11.6% of infarct size, formed electromechanical junctions with the host heart, and by 3 months contained ∼99% ventricular myocytes. A subset of animals experienced graft-associated ventricular arrhythmias, shown by electrical mapping to originate from a point-source acting as an Ectopic Pacemaker. Our data demonstrate that remuscularization of the infarcted macaque heart with human myocardium provides durable improvement in left ventricular function. Cardiomyocyte transplantation after heart attack improves contractile function in monkeys.

  • human embryonic stem cell derived cardiomyocytes restore function in infarcted hearts of non human primates
    Nature Biotechnology, 2018
    Co-Authors: Billy Chen, Xiulan Yang, James A Fugate, Faith A Kalucki, Larry Couture, Keith W Vogel, Clifford A Astley, Akiko Futakuchitsuchida, Audrey Baldessari
    Abstract:

    Cardiomyocyte transplantation after heart attack improves contractile function in monkeys. Pluripotent stem cell–derived cardiomyocyte grafts can remuscularize substantial amounts of infarcted myocardium and beat in synchrony with the heart, but in some settings cause ventricular arrhythmias. It is unknown whether human cardiomyocytes can restore cardiac function in a physiologically relevant large animal model. Here we show that transplantation of ∼750 million cryopreserved human embryonic stem cell–derived cardiomyocytes (hESC-CMs) enhances cardiac function in macaque monkeys with large myocardial infarctions. One month after hESC-CM transplantation, global left ventricular ejection fraction improved 10.6 ± 0.9% vs. 2.5 ± 0.8% in controls, and by 3 months there was an additional 12.4% improvement in treated vs. a 3.5% decline in controls. Grafts averaged 11.6% of infarct size, formed electromechanical junctions with the host heart, and by 3 months contained ∼99% ventricular myocytes. A subset of animals experienced graft-associated ventricular arrhythmias, shown by electrical mapping to originate from a point-source acting as an Ectopic Pacemaker. Our data demonstrate that remuscularization of the infarcted macaque heart with human myocardium provides durable improvement in left ventricular function.

  • human embryonic stem cell derived cardiomyocytes restore function in infarcted hearts of non human primates
    Nature Biotechnology, 2018
    Co-Authors: Yen Wen Liu, Billy Chen, Xiulan Yang, James A Fugate, Faith A Kalucki, Keith W Vogel, Clifford A Astley, Akiko Futakuchitsuchida, Larry A Couture, Audrey Baldessari
    Abstract:

    Pluripotent stem cell-derived cardiomyocyte grafts can remuscularize substantial amounts of infarcted myocardium and beat in synchrony with the heart, but in some settings cause ventricular arrhythmias. It is unknown whether human cardiomyocytes can restore cardiac function in a physiologically relevant large animal model. Here we show that transplantation of ∼750 million cryopreserved human embryonic stem cell-derived cardiomyocytes (hESC-CMs) enhances cardiac function in macaque monkeys with large myocardial infarctions. One month after hESC-CM transplantation, global left ventricular ejection fraction improved 10.6 ± 0.9% vs. 2.5 ± 0.8% in controls, and by 3 months there was an additional 12.4% improvement in treated vs. a 3.5% decline in controls. Grafts averaged 11.6% of infarct size, formed electromechanical junctions with the host heart, and by 3 months contained ∼99% ventricular myocytes. A subset of animals experienced graft-associated ventricular arrhythmias, shown by electrical mapping to originate from a point-source acting as an Ectopic Pacemaker. Our data demonstrate that remuscularization of the infarcted macaque heart with human myocardium provides durable improvement in left ventricular function.

  • Human embryonic stem cell–derived cardiomyocytes restore function in infarcted hearts of non-human primates
    Nature biotechnology, 2018
    Co-Authors: Yen Wen Liu, Billy Chen, Xiulan Yang, James A Fugate, Faith A Kalucki, Akiko Futakuchi-tsuchida, Keith W Vogel, Clifford A Astley, Larry A Couture, Audrey Baldessari
    Abstract:

    Pluripotent stem cell-derived cardiomyocyte grafts can remuscularize substantial amounts of infarcted myocardium and beat in synchrony with the heart, but in some settings cause ventricular arrhythmias. It is unknown whether human cardiomyocytes can restore cardiac function in a physiologically relevant large animal model. Here we show that transplantation of ∼750 million cryopreserved human embryonic stem cell-derived cardiomyocytes (hESC-CMs) enhances cardiac function in macaque monkeys with large myocardial infarctions. One month after hESC-CM transplantation, global left ventricular ejection fraction improved 10.6 ± 0.9% vs. 2.5 ± 0.8% in controls, and by 3 months there was an additional 12.4% improvement in treated vs. a 3.5% decline in controls. Grafts averaged 11.6% of infarct size, formed electromechanical junctions with the host heart, and by 3 months contained ∼99% ventricular myocytes. A subset of animals experienced graft-associated ventricular arrhythmias, shown by electrical mapping to originate from a point-source acting as an Ectopic Pacemaker. Our data demonstrate that remuscularization of the infarcted macaque heart with human myocardium provides durable improvement in left ventricular function.

George J. Rozanski - One of the best experts on this subject based on the ideXlab platform.

  • Atrial Ectopic Pacemaker escape mediated by phasic vagal nerve activity.
    American Journal of Physiology-Heart and Circulatory Physiology, 1991
    Co-Authors: George J. Rozanski
    Abstract:

    Effects of vagal nerve activity on atrial Ectopic Pacemaker foci were studied in vitro in strips of rabbit tricuspid valve. Transmembrane potentials were recorded from Pacemaker and working atrial ...

  • Atrial Ectopic Pacemaker escape mediated by phasic vagal nerve activity.
    The American journal of physiology, 1991
    Co-Authors: George J. Rozanski
    Abstract:

    Effects of vagal nerve activity on atrial Ectopic Pacemaker foci were studied in vitro in strips of rabbit tricuspid valve. Transmembrane potentials were recorded from Pacemaker and working atrial fibers superfused with Tyrode solution containing propranolol. Tissues were paced from the atrial muscle end at cycle lengths of 90, 70, or 50% of the intrinsic Pacemaker cycle, and postganglionic vagal nerve endings were stimulated with brief trains of pulses (200 Hz; 100-200 microseconds) through a second electrode near the Pacemaker. Vagal trains scanning diastole hyperpolarized Pacemaker and surrounding fibers to a maximum membrane potential of -74.7 +/- 1.8 mV (normal maximum diastolic potential = -75.5 +/- 1.6 mV) and elicited a period of inexcitability lasting 217.9 +/- 27.3 ms (drive cycle = 90% of Pacemaker cycle). Inexcitability was evident at critical diastolic intervals where vagal input prevented atrial impulses from activating the Pacemaker allowing spontaneous discharges to occur, i.e., escape, late in diastole. Besides inexcitability, incidence and timing of escape impulses were determined by cumulative effects of drive cycle length, vagal stimulus, and subthreshold electrotonic input on intrinsic Pacemaker cycle. These data suggest that phasic vagal stimuli may transiently protect atrial Ectopic Pacemaker foci from conducted sinus impulses by rendering Pacemaker and surrounding fibers inexcitable. In the setting of a long sinus (drive) cycle length, phasic vagal activity may result in spontaneous discharges manifest as late atrial premature beats.

Tetsuro Sakai - One of the best experts on this subject based on the ideXlab platform.

  • Optical mapping analysis of the spatiotemporal pattern of experimental tachyarrhythmia in improved isolated rat atrium preparation.
    The journal of physiological sciences : JPS, 2008
    Co-Authors: Tetsuro Sakai
    Abstract:

    We have studied the experimental tachyarrhythmia in an improved isolated rat atrial preparation for the optical mapping of excitation spread. The atrial preparation, including the right or left auricle, was dissected from the adult rat heart, and an artificial hole was made in the center of the preparation. The preparation was then stained with a fast merocyanine-rhodanine voltage-sensitive dye (NK2761). Using a multi-element (16 x 16) photodiode array, the spread of excitation was assessed optically by timing the initiation of the action potential-related extrinsic absorption changes. In comparison with the intact isolated right atrial preparation, which we used previously, the mapping of the excitation spread was much easier and more precise because of the simple structure of the preparation. The electrical stimulation applied by a bipolar electrode evoked the sustained excitation with a fast rhythm, which we termed "experimental tachyarrhythmia" (ET). We optically mapped the spatiotemporal patterns of the spread of excitation during the initiation and the maintenance phases of ET. In most cases, a rotation of the excitatory wave around the artificial hole, i.e., a circus movement of the excitatory wave, was observed. These maps suggest that this circus movement resembles the basic mechanism of the tachycardia-like excitation observed in the intact isolated right atrial preparation. On the other hand, the appearance of an Ectopic Pacemaker with a fast rhythm was also observed. In some examples, two Ectopic Pacemakers appeared simultaneously. We consider that the experiment using the improved preparation is a superb in vitro model of atrial arrhythmia.

  • Optical mapping of the spread of excitation in the isolated rat atrium during tachycardia-like excitation
    Pflügers Archiv, 2003
    Co-Authors: Tetsuro Sakai
    Abstract:

    Multiple-site optical recording of membrane potential activity, using the voltage-sensitive merocyanine-rhodanine dye NK2761 and a multiple-element photodiode array, was employed to monitor action potentials in an isolated rat atrial preparation. The events of tachycardia-like excitation (TE) were evoked by electrical stimulation. The conduction pattern of excitation was assessed optically by timing the feet of optical action potentials, then maps of excitation spread patterns were made. The excitatory waves often rotated around the blocked area including the ostium of the superior vena cava. Other patterns, such as reentry without anatomical obstacles, Ectopic Pacemaker and more complex patterns, were sometimes observed. Optical mapping during the initiation phase of TE indicated that the decrease of the conduction velocity and the appearance of blocked areas contributed the establishment of TE. On the basis of the characteristics of TE, it is suggested that TE is a metastable state of atrial rhythm. TE appears to be analogous to atrial flutter.