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HEADLINE: HCM: Mutant TnT causes stress-induced ...


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  • HEADLINE: HCM: Mutant TnT causes stress-induced ...

    Copyright 2003 Cardiovascular Week via NewsRx.com and NewsRx.net
    Cardiovascular Week

    May 5, 2003


    LENGTH: 520 words

    HEADLINE: CARDIOMYOPATHY: Mutant TnT causes stress-induced ventricular
    tachycardia and AP remodeling

    Familial hypertrophic cardiomyopathy-linked mutant TnT causes stress-induced
    ventricular tachycardia and AP remodeling.

    According to recent research published in the journal Circulation Research,
    "The cardiac troponin T (TnT) I79N mutation has been linked to familial
    hypertrophic cardiomyopathy and high incidence of sudden death, despite causing
    little or no cardiac hypertrophy in patients.

    "Transgenic mice expressing mutant human TnT (I79N-Tg) have increased cardiac
    contractility, but no ventricular hypertrophy or fibrosis.

    "Enhanced cardiac function has been associated with myofilament Ca2+
    sensitization, suggesting altered cellular Ca2+ handling.

    "In the present study, we compare cellular Ca2+ transients and
    electrophysiological parameters of 64 I79N-Tg and 106 control mice in isolated
    myocytes, isolated perfused hearts, and whole animals.

    "Ventricular action potentials (APs) measured in isolated I79N-Tg hearts and
    myocytes were significantly shortened only at 70% repolarization. No significant
    differences were found either in L-type Ca2+ or transient outward K+ currents,
    but inward rectifier K+ current (IK1) was significantly decreased.

    "More critically, Ca2+ transients of field-stimulated ventricular I79N-Tg
    myocytes were reduced and had slow decay kinetics, consistent with increased
    Ca2+ sensitivity of I79N mutant fibers.

    "AP differences were abolished when myocytes were dialyzed with Ca2+ buffers
    or after the Na+-Ca2+ exchanger was blocked by Li+. At higher pacing rates or in
    presence of isoproterenol, diastolic Ca2+ became significantly elevated in
    I79N-Tg compared with control myocytes.

    "Ventricular ectopy could be induced by isoproterenol-challenge in isolated
    I79N-Tg hearts and anesthetized I79N-Tg mice. Freely moving I79N-Tg mice had a
    higher incidence of nonsustained ventricular tachycardia (VT) during mental
    stress (warm air jets)," wrote B.C. Knollmann and colleagues, Georgetown
    University, Medical Center.

    The researchers concluded: "The TnT-I79N mutation causes stress-induced VT
    even in absence of hypertrophy and/or fibrosis, arising possibly from the
    combination of AP remodeling related to altered Ca2+ transients and suppression
    of IK1."

    Knollmann and colleagues published their study in Circulation Research
    (Familial hypertrophic cardiomyopathy-linked mutant troponin T causes
    stress-induced ventricular tachycardia and Ca2+-dependent action potential
    remodeling. Circ Res, 2003;92(4):428-436).

    For additional information, contact B.C. Knollmann, Georgetown University,
    Med Center, Department Pharmacology, Division Clinical Pharmacology, 3900
    Reservoir Rd., Washington, DC 20007, USA.

    The publisher's contact information for the journal Circulation Research is:
    Lippincott Williams & Wilkins, 530 Walnut St., Philadelphia, PA 19106-3621,

    The information in this article comes under the major subject areas of
    Cardiology and Neurology.

    This article was prepared by Cardiovascular Week editors from staff and other


    LOAD-DATE: May 2, 2003
    Thanks, Tim
    Forum Administrator

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