Abnormal Function of Platelet G Proteins in Long QT Syndrome.

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 +/- 0.6 pmol/ 10(8) cells vs. 4.2 +/- 0.7 pmol/10(8) 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 +/- 6.2 pmol/10(8) cells vs. 24.8 +/- 7.4 pmol/10(8) cells (PGE1-cAMP). After addition of adrenaline, cAMP decreased to 14.2 +/- 5.8 pmol/10(8) cells vs. 16.2 +/- 7.6 pmol/10(8) 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.