摘要:

The effects of diltiazem on ventricular arrhythmias and ventricular vulnerability for fibrillation, both in the very beginning of myocardial ischemia and in the early stage of myocardial necrosis, were evaluated in 13 mongrel dogs. In part I of the study, repeated coronary occlusions were performed. Time course and extent of ventricular ectopy were continuously recorded, and changes in ventricular fibrillation threshold were assessed, both after coronary artery occlusion and release. In part II, a permanent coronary artery occlusion was performed, and the changes in frequency of ventricular arrhythmias were assessed. Diltiazem displayed strong antiarrhythmic and antifibrillatory effects on early ventricular occlusion arrhythmias. The drop in ventricular fibrillation threshold 5 min after coronary occlusion was significantly attenuated. Following the release of coronary artery obstruction, diltiazem failed to reduce the frequency of ventricular fibrillation immediately after the onset of reperfusion. However, during the early postreperfusion period, the drug was able to accelerate significantly the increase in the ventricular fibrillation threshold. Late phase ventricular arrhythmias were not influenced by the drug even when high doses were applied. The different antiarrhythmic actions of diltiazem on early and late phase ventricular arrhythmias can be assumed to be due to differences in the arrhythmogenesis at the very onset of myocardial ischemia compared to the stage of myocardial necrosis.

ISSN:0031-7012    

DOI:10.1159/000138193

出版商:S. Karger AG    

年代:1986

数据来源: Karger

摘要:

The effects of aprindine (1 × 10–7 to 4× 10–6M) were examined on membrane potential and current of rabbit sinoatrial node by means of conventional microelectrode and double microelectrode voltage clamp methods. Aprindine decreased, in a dose-dependent manner, the spontaneously firing frequency, the maximum rate of depolarization and the action potential amplitude, and prolonged the action potential duration at half-amplitude. The slope of the diastolic depolarization was also reduced by the drug. In the voltage clamp experiment, aprindine reduced the slow inward current (Isi), the time-dependent potassium current (IK) and the hyperpolarization activated current (Ih). The recovery time constant of Isi was prolonged by aprindine, while the kinetics of IK was not altered. It is indicated that aprindine does not have an effect on a specific conductance or a single current system, but that the drug exerts an inhibitory effect on the electrical activity of sinoatrial

ISSN:0031-7012    

DOI:10.1159/000138194

出版商:S. Karger AG    

年代:1986

数据来源: Karger

摘要:

We examined consecutive contractile responses of isolated rabbit pulmonary arteries during repeated exposures to either norepinephrine, histamine or KCl, with washout and relaxation between trials. For each agonist, EC50 values remained constant during consecutive determinations, but the maximum force increased after the first determination. A maximum concentration of norepinephrine or histamine produced a biphasic contraction: the fast phase increased subsequent to the first determination and was retained in a calcium-free medium, while the slow phase was unaltered during consecutive determinations and was absent in a calcium-free medium. We conclude that in the rabbit pulmonary artery: (l)the initial contractile response is a useful control for studies of sensitivity but not of maximum activity; (2) there may be a nonspecific increase in the availability of intracellular calcium after the initial contraction and relaxation, and (3) desensitization or tachyphylaxis to these agonists does not occur.

ISSN:0031-7012    

DOI:10.1159/000138195

出版商:S. Karger AG    

年代:1986

数据来源: Karger

摘要:

We examined the effects of magnesium on contractile responses of the rabbit pulmonary artery. The contractile force was determined, after applications of norepinephrine or histamine, in a normal or Ca++-free solution containing 0 mM Mg++ or 1.2 mM Mg++. In a normal solution, Mg++ increased the EC50 value for histamine, but did not alter the EC50 value for norepinephrine or the maximum force induced by norepinephrine or histamine. Contractile responses to norepinephrine and histamine were equally reduced by a Ca++-free, Mg++-free solution, and were further reduced by a Ca++-free solution containing Mg++, but with a greater reduction in the response to histamine than in the response to norepinephrine. The results indicate that in the pulmonary artery, Mg++ alters the sensitivity to histamine but not to norepinephrine, and may differentially inhibit bound Ca++ release by norepinephrine and histamine.

ISSN:0031-7012    

DOI:10.1159/000138196

出版商:S. Karger AG    

年代:1986

数据来源: Karger

摘要:

Diabetes mellitus is known to produce alterations in vascular reactivity. In the present study we have examined the effects of short-term diabetes on histamine-induced relaxation of isolated mesenteric arteries, and the role of the endothelial cell layer in this response. Removal of the endothelium completely abolished the histamine relaxation effect in both diabetic and age-matched control rats. In contrast, vessels isolated from streptozotocin-diabetic rats were supersensitive to histamine, and this relaxation was mediated only through the H1-preceptors. The present findings suggest that histamine-induced relaxation of rat mesenteric arteries is dependent upon endothelial cell processes which are enhanced in arteries from STZ-diabetic rats.

ISSN:0031-7012    

DOI:10.1159/000138197

出版商:S. Karger AG    

年代:1986

数据来源: Karger

摘要:

Concentration-response curves to potassium chloride, phenylephrine, serotonin and calcium chloride were obtained from rat aortic strips subjected to preloads of 0.75, 1.5 or 3.0 g. The sensitivity of the aortic smooth muscle to potassium chloride, phenylephrine and serotonin increased with increasing preload; whereas the calcium chloride concentration-response curves of K+-depolarized strips were unaffected by preload. These results demonstrate that the sensitivity of rat aortic smooth muscle to many vasoactive agents is a function of preload and also indicate that an alteration in the influx of external Ca2+ is not sufficient to explain the effect of preload on sensitivity.

ISSN:0031-7012    

DOI:10.1159/000138198

出版商:S. Karger AG    

年代:1986

数据来源: Karger

摘要:

Buspirone (BP), a newly developed antianxiety agent, forms 1-(2-pyrimidinyl)-piperazine (PmP) during its biotransformation in rats and man. After oral administration of pharmacologically effective doses of BP-hydrochloride to rats (1 and 10 mg/kg), the metabolite appears in significant amounts in body fluids and tissues; it is highly concentrated in the central nervous system, the brain-to-plasma concentration ratios being approximately 5 at the time of the maximum concentrations (Cmax). In man given the anxiolytic dose (20 mg) of BP the metabolite reaches higher plasma Cmax values than its parent drug. Its plasma elimination t1/2 is more than double that for BP. These results, together with the fact that PmP is biochemically and pharmacologically active, suggest that the metabolite may contribute significantly to the central effects of the parent drug.

ISSN:0031-7012    

DOI:10.1159/000138199

出版商:S. Karger AG    

年代:1986

数据来源: Karger

摘要:

The effect of administration of thyroxine (T4) and estradiol benzoate (EB), alone and combined (EB + T4), to female rats for 35 days on their serum concentrations of T4 and triiodothyronine (T3), and on the rate of conversion of T4 to T3 by homogenates of their liver and kidneys was studied. Administration of T4 (50 μg/kg b.w./day) resulted in an increase, while administration of EB (57 μg/kg b.w./day) resulted in a decrease in serum levels of T4. In EB + T4-treated rats, the serum concentration of T4 was less than that of either the T4-treated or control groups, while the serum T3 concentration was greater than that of the EB-treated group. Administration of T4 resulted in a rate of hepatic generation of T3 which was 180% of control, while the rate of renal T3 generation was 152% of control. Activity of T4 5’-monodeiodinase in hepatic homogenates was not affected significantly by administration of EB, while that in renal homogenates was inhibited by 44%. Administration of T4 in combination with EB resulted in a rate of conversion of T4 to T3 by hepatic homogenates which was 334% of control and significantly higher than that achieved by T4 alone. The rate of renal T3 generation by this group was 129% of control, but less than that achieved by administration of T4 alone. Administration of EB + T4 potentiated the effect of T4 on hepatic T4 to T3 converting activity and is likely responsible for the reduction in serum T4 concentration of these anim

ISSN:0031-7012    

DOI:10.1159/000138200

出版商:S. Karger AG    

年代:1986

数据来源: Karger

摘要:

Using the method of staining mucus with Alcian blue and destaining it with magnesium chloride, it was found that intragastric administration of carbenoxolone in mice did not significantly affect duodenal mucus synthesis at doses which remarkably increased gastric mucus synthesis. However, in vitro study showed that carbenoxolone significantly stimulated both gastric and duodenal mucus synthesis. It is suggested that carbenoxolone may also effectively increase mucus synthesis and probably accelerate ulcer healing in the duodenum if sufficient amounts can escape gastric absorption and reach this region.

ISSN:0031-7012    

DOI:10.1159/000138201

出版商:S. Karger AG    

年代:1986

数据来源: Karger