The effects of alinidine,an N-allyl derivative of clonidine,on regional myocardial perfusion and performance in the pig with or without atrial pacing

The effects of alinidine (0.2–6.0 mg · kg^?1), an N-allyl derivative of clodnidine, were investigated on systematic and regional haemodynamics, in particular myocardial perfusion and performance, in the domestic pig, during or in the absence of atrial pacing. The drug had a pronounced bradycardic action and also caused dose-dependent reductions in the maximum rate of rise in left ventricular pressure (max LVdP/dt) cardiac output (CO), arterial blood pressure and in the mean velocity of systolic wall thickening (v?_SWT) in the absence of atrial pacing. Since the duration of systole was prolonged by alinidine, the total wall thickening during systole (SWT) remained unchanged until the highest dose was given. When the heart rate was kept constant by atrial pacing, there were no changes in the maxLVdP/dt, CO or v?_SWT with lower doses (< 0.4 mg · kg^?1) of alinidine. With higher doses, however, there was a significant reduction in these variables, demonstrating a clear negative inotropic action of the drug. The drecrease in CO was entirely at the expense of its nutrient fraction (NCO), since systematic arteriovenous anastomotoc flow remained unchanged. However, the reduction in NCO did not hamper tissue oxygenation either because of autoregulation within blood vessels (cerebral and renal), or because the tissues were able to extract more O₂ from the blood. Similarly, despite the reduction of myocardial perfusion, no imbalance in the myocardial oxygen supply-demand relationship was noticed due to a simultaneous reduction of th myocardial work in both unpaced and paced hearts. Morevoer, the changes in the intramyocardial blood flow were quite uniform. It is concluded that alinidine has a negative chronotropic and, in higher doses, a negative inotropic action. The cardiovascular profile of the drug suggests that it could be useful in patients with ischaemic heart disease.     

呋喃丙吡啶对再灌注心肌顿抑兔血小板聚集和血压的影响

目的：探讨心肌顿抑发生后血流动力学和血小板聚集率的变化，以及钙通道拮抗剂呋喃丙吡啶对心肌顿抑兔的保护作用。方法：经冠状动脉结扎法建立兔心肌顿抑模型。用药组缺血前用呋喃丙吡啶静脉给药。结果：对照组再灌注后１５ｍｉｎ血浆最大血小板聚集率达高峰（６１．７６％±９．２２％），用药组同一时间点血浆最大血小板聚集率较对照组低（４０．２３％±５．３９％，Ｐ＜０．０１）。对照组血压较缺血前明显下降（Ｐ＜０．０５），用药组：Ⅰ组（１ｍｇ·ｋｇ－１）血压变化与对照组无统计学差异，Ⅱ组（３ｍｇ·ｋｇ－１）缺血后舒张压下降明显与对照组相比差异显著，随着再灌注时间延长舒张压逐步回升。结论：心肌顿抑发生后伴有血流动力学变化及血小板聚集率增高，缺血前静脉应用呋喃丙吡啶治疗对心肌损伤具有保护作用。     

呋喃丙吡啶对心肌顿抑兔心肌肾素、血管紧张素Ⅱ及去甲肾上腺素的影响

目的研究心肌局部肾素、血管紧张素Ⅱ（ＡｎｇⅡ）及去甲肾上腺素（ＮＥ）在心肌顿抑发病中的作用，以及呋喃丙吡啶（Ｆ３）对心肌顿抑是否具有保护作用。方法采用冠状动脉结扎法建立兔心肌顿抑模型，用放射免疫法测定肾素、ＡｎｇⅡ及ＮＥ的变化，缺血前用呋喃丙吡啶静脉给药。结果心肌缺血后局部肾素活性有升高趋势，再灌注后心肌局部肾素活性显著高于正常对照组。心肌局部ＡｎｇⅡ含量明显高于正常对照组。心肌ＮＥ含量明显升高。缺血前静脉推注呋喃丙吡啶可以降低心肌顿抑时心肌局部ＡｎｇⅡ及ＮＥ的产生。结论心肌局部肾素，ＡｎｇⅡ及ＮＥ在心肌顿抑的发病中具有重要意义，缺血前静脉应用呋喃丙吡啶防治可能是有益的。     

Evaluation of the efficacy of metaclazepam and its effects on sleep,psychomotor performance and cognitive function in anxious patients

The effects of single and multiple doses of metaclazepam were investigated in 60 anxious patients. A 15 mg nocturnal dose of metaclazepam was compared to two daily doses (5 mg in the morning and 10 mg at bedtime) in terms of efficacy and effects on various aspects of sleep, cognitive function and psychomotor performance. Anxiolytic efficacy was assessed by means of questionnaires, including the Self Rating Anxiety Scale of Zung, State Trait Anxiety Inventory of Spielberger, and a modified version of the Hamilton Anxiety Rating Scale. Hypnotic activity was evaluated using a clinical rating of insomnia questionnaire. The psychometric battery consisted of tests of Critical Flicker Fusion, Choice Reaction Time and Digit Span. In terms of clinical efficacy, metaclazepam administered in either dosage regimen demonstrated a good anxiolytic activity profile. Both dosage regimens were effective in improving the quality and quantity of sleep, however the number of intermittent awakenings were significantly higher with the daily divided dose. In addition, the nocturnal administration of metaclazepam did not appear to be associated with any undesirable side effects or decrements in psychomotor performance the following morning. In conclusion, it appears that a 15 mg bedtime dose of metaclazepam is efficacious in relieving anxiety without impairing psychomotor performance the following morning. © 1998 John Wiley & Sons, Ltd.