DCTQ (SK&F 64139) is a potent inhibitor of both adrenal and central nervous system (CNS) phenylethanolamine N-methyltransferase (PNMT). In animal studies, a plasma level of 0.35 microgram/ml was associated with 50% inhibition of both adrenal and central PNMT. We performed single-dose phase I studies with DCTQ in man. Plasma drug levels up to 6.26 microgram/ml were readily obtained. There were few subjective and no objective clinical changes. DCTQ did not alter blood pressure or cause CNS symptoms in man. Furthermore, resting plasma and urinary catecholamines did not change after DCTQ. The study suggests that acute inhibition of PNMT under resting conditions is without significant clinical effect.
Technique and errors of quantitative single plane ventriculography (SPV), and the methods of Dodge and Sandler (Dodge et al, 1962; Sandler and Dodge, 1968) and Greene et al (1967) for determining left ventricular (LV) volume by SPV were evaluated in the intact dog. Stroke volume (SV) and cardiac output (Q) by ventriculography were compared with those obtained by the Fick and dye dilution methods, and their combination. The end-diastolic (EDV) and end-systolic volume (ESV) corrected by appropriate regression equations, the SV (SV=EDV - ESV), and the ejection fraction (EF) were: Dodge and Sandler, 2.26 1.35, 0.91 ml/kg, and 0.42; Greene et al, 2.41, 1.50, 0.91 ml/kg, and 0.39. Using adequate methods, accurate correction for x-ray image magnification, and the appropriate regression equations the standard error of LV volume calculation by single plane radiography, due to unavoidable technical inaccuracies, should not exceed 10% for a single measurement and 5% for the average of two or more successive cardiac cycles. The systematic overestimation of LV volume inherent in ventriculography, and caused by the addition of contrast medium, should not exceed 5% of the true value.
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