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21.
Pinacidil uptake and effects in the isolated rabbit heart 总被引:1,自引:0,他引:1
The myocardial accumulation of pinacidil showed one-compartment characteristics with a half-time of 1.11 min., whereas the disposition followed three-compartment kinetics with half-times for the relevant two redistributory and the terminal phases of 0.39, 1.51 and 5.44 min., respectively. At a steady-state drug concentration in the perfusate of 6.12 nmol ml-1, the average concentration of pinacidil in the myocardium was 20.6 nmol g-1. The accumulated amount could predictically be referred with 57% to a central and 31 and 12% to two peripheral (deeper) drug pools. The pharmacodynamic effects of pinacidil in the isolated perfused rabbit heart were studied at stepwise increasing concentrations from 0.15 to 100 microM. Coronary flowrate increased initially up to 24.5% at 1.5 microM pinacidil and then gradually decreased. Amplitude and velocity of contraction were both inhibited in a biphasic way up to 92.7 and 94.1%, respectively. Apparent dynamic steady states developed within 13-15 min. The computer-derived inhibitory Em-values related to the first phase were 49.2 and 52.4% and those related to the second phase were 111.7 and 108.3%, respectively. Heart frequency decreased monophasically and exhibited an inhibitory Em-value of 19.6%. Oxygen consumption decreased at pinacidil concentrations higher than 15 microM and the Em-value was 69.7%. The frequency-corrected QT-interval decreased biphasically and the related inhibitory Em-values were 8.6 and 58.7%. The QRS-interval did not change and the PQ-interval only showed a minor increase at the highest pinacidil concentration. Our findings are compatible with the concept of pinacidil being a potassium channel opener. 相似文献
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E J Nielsen 《Annals of emergency medicine》1992,21(7):880-882
Tropical pyomyositis, though common in Africa, South America, and the South Pacific, is relatively rare in North America. Reported is the case of a patient who developed chest wall muscle abscesses after sustaining minor chest wall muscle trauma and presented to the emergency department appearing acutely ill. He was treated surgically with irrigation and debridement of the abscesses as well as with antibiotics and recovered fully over a seven-month course. This case illustrates important aspects of tropical pyomyositis with a discussion of the natural history of this disease as well as diagnostic modalities and treatment options for this virulent infectious process that is usually caused by penicillin-resistant Staphylococcus aureus. 相似文献
24.
H. K. Iversen T. H. Nielsen K. Garre P. Tfelt-Hansen J. Olesen 《European journal of clinical pharmacology》1992,42(1):31-35
Summary The aim of the present study was to compare the ability of different doses of isosorbide-5-mononitrate (5-ISMN) to cause dilatation of medium sized and small arteries, and to examine the intensity and duration of any headache produced. Ten healthy volunteers each received 3 doses of 5-ISMN and placebo on separate days. The diameters of the radial and superficial temporal arteries were repeatedly measured with high frequency ultrasound and pain was scored using a 10 point verbal scale.A clear dose-relationship was found for plasma concentrations and headache, and for changes in the diameter of the temporal artery, but not for the radial artery.It is concluded that headache after 5-ISMN is caused by arterial dilatation or by mechanisms responsible for the arterial dilatation. Ultrasound monitoring of arterial diameters is an important and sensitive tool in the evaluation of nitrates and other vasodilators. 相似文献
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Direct condensation of 2-deoxy-D-ribose (1) with mercaptans using the P4O10/H2O/Bu3N reagent in chloroform resulted in coupling at C-3 to give the anomeric mixtures of the corresponding pentopyranoses 2 and pentofuranoses 3. After acetylation with acetic anhydride in dry pyridine of these 3-alkylthio pentofuranoses, coupling with the nucleobases uracil, thymine, and cytosine in accordance with the Friedel-Crafts catalyzed silyl Hilbert-Johnson method yielded the acetylated D-erythro nucleosides 7 as anomeric mixtures, separable only by means of chromatography either before or after deprotection with ammonia. The nucleosides 8a-e were devoid of any activity against HSV-1 and HIV-1. 相似文献
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The effect of prolonged hypercapnia on carotid chemoreceptor discharge frequency has not been elucidated. In addition, the effect of acute hypercapnia on chemoreceptor discharge has not been determined in the goat, a species commonly used for ventilatory control studies. Therefore, we determined the effects of acute and prolonged normoxic-hypercapnia on single fiber output of the carotid body of chloralose anesthetized goats. The animals were paralyzed and artificially ventilated. The average acute response curve for 12 single fibers was linear over the range of 30-80 Torr PaCO2 with a mean slope of 0.115 +/- 0.057 (SD) imp.sec-1.Torr-1 PaCO2. Elevated discharge frequency was maintained during prolonged (up to 240 min, n = 11) steady-state hypercapnia (X PaCO2 = 85 Torr). No systematic time-dependent changes in afferent discharge frequency occurred during the period. The findings obtained during sustained hypercapnia are in contrast to the time-dependent increase in carotid body activity seen previously in our laboratory with prolonged normocapnic-hypoxia of up to 240 min duration. 相似文献
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