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https://hdl.handle.net/2440/8936
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Type: | Journal article |
Title: | Short-term myocardial uptake of d- and l-Sotalol in humans: relation to hemodynamic and electrophysiologic effects |
Author: | Ritchie, R. Sallustio, B. Hii, J. Horowitz, J. |
Citation: | Journal of Cardiovascular Pharmacology, 1998; 31(6):876-884 |
Publisher: | LIPPINCOTT WILLIAMS & WILKINS |
Issue Date: | 1998 |
ISSN: | 0160-2446 1533-4023 |
Abstract: | The myocardial concentration of many cardioactive drugs has been identified as an important determinant of their short-term effects in previous studies. Although sotalol is frequently administered via short-term intravenous injection, no previous studies had sought to correlate its uptake by the heart with its various effects. We determined the time course of short-term uptake of d,l-sotalol by human myocardium in vivo and investigated the relation between myocardial content of sotalol and the short-term hemodynamic, electrocardiographic, and electrophysiologic effects of the drug. Sixteen patients received a 20-mg intravenous bolus of sotalol at the time of diagnostic cardiac catheterization. Myocardial content of d- and l-sotalol (by using a paired transcoronary sampling technique) and the short-term hemodynamic and electrophysiologic effects of the drug were determined < or = 20 min after injection. Myocardial accumulation of sotalol was not enantioselective, proceeded very rapidly (maximal at 0.74 +/- 0.10 min, representing 2.05 +/- 0.45% of the total injected dose), and was not significantly influenced by left ventricular systolic function or the extent of coronary artery disease. Approximately one third of peak myocardial content was still present 17.5 min after sotalol administration. Maximal effects of the drug (reduction in spontaneous heart rate, p < 0.005; reduction in maximal rate of LV pressure increase (LV+dP/dtmax, p < 0.005); and prolongation of PR intervals, p < 0.02) were delayed by approximately 10 min relative to maximal myocardial sotalol content. The significant prolongation of AH intervals (p < 0.01) and atrioventricular nodal effective refractory periods (p < 0.0002) that was observed was also maximal 10 min after administration of sotalol. Thus a consistent delay between myocardial sotalol content and the short-term effects of the drug was observed. In conclusion, the accumulation of both d- and l-sotalol by the human myocardium is more rapid than that of any other agent studied to date, with considerable hysteresis between myocardial drug uptake and subsequent cardiac effects. |
Keywords: | Myocardium Humans Myocardial Ischemia Sotalol Adrenergic beta-Antagonists Stereoisomerism Adult Aged Middle Aged Female Male |
DOI: | 10.1097/00005344-199806000-00011 |
Published version: | http://dx.doi.org/10.1097/00005344-199806000-00011 |
Appears in Collections: | Aurora harvest 4 Medicine publications |
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