The American journal of cardiology
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Lorcainide is an antiarrhythmic drug with unusual pharmacokinetics and an active metabolite, norlorcainide, which complicate oral drug loading. In order to characterize the accumulation of lorcainide and norlorcainide and to define the onset of antiarrhythmic action during lorcainide loading, 9 patients with frequent ventricular ectopic beats were studied. During lorcainide loading with 100 mg orally twice daily, frequent ambulatory electrocardiographic recordings were monitored and blood samples for drug concentrations were determined. ⋯ Norlorcainide had a half-life of 26.5 +/- 7.2 hours and was estimated to come to steady state after 7 to 10 days. There was considerable intersubject variation in time of onset of antiarrhythmic response (2 to more than 4.5 days) and a 4- to 5-fold range of intersubject variation in threshold therapeutic plasma concentration (lorcainide 40 to 200 ng/ml, norlorcainide 80 to 300 ng/ml). These observations suggest that lorcainide should be started at low doses and the dose should not be increased more frequently than once a week.
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This study was designed to more clearly define the relation between various invasive hemodynamic measurements and left ventricular (LV) timing intervals, ejection rate and filling rate derived from the radionuclide angiographic volume curve. Twenty-eight patients were studied with simultaneous intracardiac micromanometer pressure and dP/dt recordings, gated radionuclide angiography and M-mode echocardiography. These techniques permitted multiple variables of systolic and diastolic function to be measured at a constant atrial paced rate of 100 beats/min. ⋯ A weaker correlation existed between the time constant of LV relaxation and the peak filling rate (r = -0.49) and between the LV end-diastolic pressure and the peak filling rate (r = -0.62). There was no correlation between the modulus of chamber stiffness and filling rates, and no association was observed between the time to peak filling rate and the hemodynamic variables. Thus, under the conditions studied, the measured peak ejection and filling rate, determined from the radionuclide angiographic volume curve, correlated well with accepted invasive hemodynamic measurements.