Abnormal Function of Platelet G Proteins in Long QT Syndrome

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概要

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• Several hypotheses have been proposed for the pathophysiology of the congenital long QT syndrome, however, the underlying mechanism has not yet been elucidated. This study evaluated G protein function in patients with congenital long QT syndrome (LQTS) and compared it with that of normal subjects.Platelet-rich plasma was collected and the cyclic AMP (cAMP) level of platelets was measured in three conditions utilizing radioimmunoassay: the basal state (Basal cAMP), after stimulation by PGE1 (PGE1-cAMP), and after stimulation by PGE1 followed by inhibition by adrenaline (Adr-cAMP), and the results were compared between 7 LQTS patients and 10 healthy volunteers (control). Gs function was defined as (PGE1-cAMP)/(Basal cAMP) and Gi function as {(PGE1-cAMP)-(Adr-cAMP)}/(PGE1-cAMP).Basal cAMP was lower in patients than in the controls: 2.9±0.6pmol/108 cells vs. 4.2±0.7pmol/108 cells (p<0.05). The increase in cAMP after PGE1 was similar in the two groups but the peak was lower in the patients: 16.8±6.2pmol/108 cells vs. 24.8±7.4pmol/108 cells (PGE1-cAMP). After addition of adrenaline, cAMP decreased to 14.2±5.8pmol/108 cells vs. 16.2±7.6pmol/108 cells and the change was significantly smaller in the patients than in the controls: 0.17±0.12 vs. 0.38±0.16 (p<0.05).Basal cAMP was weakly correlated with sinus cycle length (r=-0.48, p>0.3) and QTc was correlated with Gs function (r=0.52, p>0.3) but not with Gi function. Patients with associated Torsade de Pointes had a significantly lower Gi function compared to those without (p<0.05).In LQTS patients, G protein function was abnormal and the abnormality was associated with clinical characteristics of long QT syndrome. The relationship between the abnormal G protein function and the regulation of the repolarization of the ventricular myocardium needs to be studied further.

著者

• Fuse Ichiro

  First Department of Internal Medicine

• Shibata Akira

  First Department Of Internal Medicine Niigata University Niigata Case Western Reserve University

• Aizawa Yoshifusa

  First Department Of Internal Medicine Niigata Universaity School Of Medicine

• FUSE Ichiro

  First Department of Internal Medicine, Niigata University School of Medicine

• WASHIZUKA Takashi

  First Department of Internal Medecine, Niigata University School of Medicine, Niigata, Japan.

• AIZAWA Yoshifusa

  First Department of Internal Medecine, Niigata University School of Medicine, Niigata, Japan.

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