抗细胞间粘附分子-1单抗对异丙肾上腺素 所致心肌损害的保护作用

为探讨抗细胞间粘附分子－１（ＩＣＡＭ－１）单抗对异丙肾上腺素（异丙肾）所致ＳＤ大鼠心肌损害的保护作用，在光镜下观察了经抗ＩＣＡＭ－１单抗预处理和未经预处理，均通过多次大剂量异丙肾导致的大鼠心肌损害（ＨＥ染色）的程度。结果：心肌损害程度处理组（多为Ⅱ级，５／６只）与对照组（多为Ⅲ级，６／７只）之间比较，差异有非常显著性意义（Ｐ＜０．０１）。另外还发现，处理组心肌损伤区的粒细胞聚集明显轻于对照组。提示抗ＩＣＡＭ－１单抗对异丙肾引起的心肌损害具有保护作用。     

Electrophysiological and electropharmacological studies in pre-excitation syndromes: results with propafenone therapy and isoproterenol infusion testing.

To study the electrophysiological effects of oral propafenone on accessory pathways and determine the potential for catecholamine-mediated reversal of these effects, comprehensive electrophysiology studies (EPS) were conducted in 11 patients with manifest (n = 9) or concealed (n = 2) pre-excitation syndrome. EPS were performed at baseline (in the drug-free state), after oral propafenone loading, and with isoproterenol infusion during propafenone therapy. The study group included 10 men and 1 woman with a mean age of 39 +/- 13 years, who presented with symptoms of palpitations (n = 6), presyncope (n = 3) and syncope (n = 2). The clinical arrhythmia was atrioventricular reciprocating tachycardia (n = 6), atrial flutter/fibrillation (n = 3), or both (n = 2). During the baseline EPS the accessory pathway location was identified as left (n = 6) or septal (n = 5). The mean anterograde effective refractory period was 265 +/- 42 ms, the shortest pre-excited RR interval 259 +/- 20 ms and the retrograde refractory period 258 +/- 39 ms. Orthodromic atrioventricular reciprocating tachycardia was induced in 10 patients (mean cycle length = 324 +/- 31 ms). Antidromic reciprocating tachycardia was induced in one patient (cycle length = 340 ms). In all the 11 patients EPS were repeated after 4 days of oral propafenone loading (668 +/- 226 mg daily) when drug steady state was expected to have been achieved. One additional patient had baseline EPS but developed clinical arrhythmia recurrences after propafenone loading and thus he was excluded from the study; follow-up EPS were conducted on procainamide.(ABSTRACT TRUNCATED AT 250 WORDS)     

多阶段倾斜试验在不明原因晕厥中的诊断价值

本研究选择了３５名不明原因晕厥患者为研究组，２０名窦性心动过缓患者（窦缓）为对照组，观察了多阶段倾斜试验在不明原因晕厥中的诊断价值。倾斜８０°分别在无异丙肾上腺素（异丙肾）和异丙肾剂量为１μｇ／ｍｉｎ，２μｇ／ｍｉｎ，３μｇ／ｍｉｎ不同浓度静滴，分为４个阶段进行。３５名不明原因晕厥患者平均年龄（４０±８）岁。阳性２８名，阴性７名，阳性率为８０％。２０例窦缓患者平均年龄（４９±７）岁，阳性２名，阴性１８名，阳性率１０％。两组之间差别有显著性意义（Ｐ＜０．０１）。倾斜试验合用异丙肾可提高阳性率。９０％阳性患者在≤３μｇ／ｍｉｎ异丙肾剂量５ｍｉｎ内出现阳性结果。心率－血压乘积值显著下降有助于鉴别阳性或阴性结果。其阳性预测值≤１．２×１０３ｋＰａ／ｍｉｎ，阴性预测值≥１．３×１０３ｋＰａ／ｍｉｎ。     

异丙肾上腺素超声负荷试验对二尖瓣球囊扩张术后疗效的评价

目的对２４例二尖瓣狭窄患者行球囊扩张术前后作异丙肾上腺素超声心动负荷试验，拟进一步评价经皮穿刺二尖瓣球囊扩张术的疗效。方法在患者安静休息的基础心率及应用异丙肾上腺素静脉点滴后不同心率状态下测定二尖瓣口面积（ＭＶＡ）、二尖瓣跨瓣压差（ＭＶＧ）及心排血量（ＣＯ）。结果二尖瓣球囊扩张使得静息状态下的瓣口面积（０．９１±０．２８升至１．８７±０．２３ｃｍ２，Ｐ＜０．０１），跨瓣压差（１２．５±６．３降至３．９±１．９ｍｍＨｇ，Ｐ＜０．０５），及心排血量（３．９３±１．４４升至４．７３±１．０１ｌ／ｍｉｎ，Ｐ＜０．０５）发生明显变化。在球囊扩张前做异丙肾上腺素试验时，虽然随着心率加快，跨瓣压差明显升高（Ｐ＜０．０１），但瓣口面积及心排血量并无显著改善（Ｐ＞０．０５）。但球囊扩张术后再做异丙肾上腺素试验时，随着心率加快，跨瓣压差升高，瓣口面积（从１．８５±０．４８升至２．３２±０．３６ｃｍ２，Ｐ＜０．０１）及心排血量（从４．４８±１．９８升至７．５５±１．９０Ｌ／ｍｉｎ，Ｐ＜０．０１）均明显进一步改善。结论异丙肾上腺素超声负荷试验能进一步评价二尖瓣球囊扩张术后的贮备功能，且该法安全、重复性强     

Transdermal Delivery of Isoproterenol HC1: An Investigation of Stability,Solubility, Partition Coefficient,and Vehicle Effects

Effects of solubility, partition coefficient, and selected adjuvants (propylene glycol and Azone) on percutaneous penetration of isoproterenol HC1 have been investigated using human cadaver skin. Isoproterenol was found to be stable (<1% decomposition) for 24 hr at 22 ± 0.5°C in the pH range 1 to 7 in the following solvents: water, normal saline, propylene glycol and a series of propylene glycol–water mixtures (10, 20, 40, and 60%; v/v); however, decomposition was significant beyond pH 8. In normal saline, the rate of decomposition increased significantly with an increase in temperature to 37°C. The solubility of isoproterenol HC1 decreased and its skin/vehicle partition coefficient increased with increasing proportions of propylene glycol in the vehicle, while the product of the solubility and partition coefficient appeared to plateau at 20% propylene glycol in water. Optimal penetration enhancing effects of Azone were seen when incorporated at a concentration of 1% (v/v) in the 20% (v/v) propylene glycol–water blend and, more significantly, when skin was pretreated with pure Azone for 60 min prior to application of the drug formulation.     

High alkaline phosphatase activity in isoproterenol stimulated fibroblast cultures from patients with numerically unbalanced chromosomal aberrations

Treatment of cultured fibroblasts from patients with unbalanced chromosomal aberrations with a mixture of isoproterenol, theophylline and ascorbic acid resulted after 48 hours in an at least three-fold increase of alkaline phosphatase activity on a per cell basis, whereas cells from normal healthy individuals did not show this dramatic response. Cells were studied from patients with trisomy 21 (14 cases), trisomy 18 (3 cases), trisomy 13 (1 case), pentasomy X (1 case), Turner syndrome (2 cases), and Klinefelter syndrome (1 case), and no exception was noted. The mechanism of this phenomenon is not clear, but it is speculated that increased cyclic-AMP levels caused by the action of isoproterenol on adenylcyclase may account for excessive reactions of unbalanced cells as compared to normal cells. This simple biochemical diagnostic procedure might become useful in screening programs for unbalanced chromosomal abberations.     

Receptor binding sites for beta-adrenergic ligands on human erythrocytes

Affinity, specificity and kinetics for [3H]-DHA binding to human red cell ghost were determined by ultra-filtration. At 2 degree an apparent dissociation constant of 0.96 nM was found with maximum specific binding of 29 fmoles per mg protein. The low dissociation constant was confirmed by kinetic studies with a value of 0.86 nM. Propranolol and isoproterenol inhibited [3H]-DHA binding stereo specifically. Agonist potency (IPR greater than EPI greater than NE) indicated that human erythrocytes had an adrenergic receptor of beta-2 subtype. Isoproterenol in the presence of theophylline resulted in a concentration-dependent increase of intracellular cAMP levels in intact cells. Basal and maximal levels were 2.3 and 7.5 pmoles/108 cells respectively after 2.5 min stimulation. EC50 for isoproterenol was 0.27 microM. Propranolol shifted the isoproterenol concentration response curve to the right. The present results show that human erythrocytes possess recognition sites for beta-adrenergic ligands with binding characteristics similar to that of adrenergic receptors of beta-2 subtype. At least a small number of these binding sites are functionally coupled to adenylate cyclase.     

Continuous light paradoxically reduces catecholamine-induced melatonin production

Exposure of rats to continuous light for 14 days reduced the stimulation of melatonin content in the pineal gland produced by either isoproterenol administration or exposure to darkness. Since continuous light has been reported to enhance many intermediate biochemical events leading to the synthesis of melatonin, these results demonstrate the importance of examining the end-product of an organ when evaluating the physiological significance of biochemical changes in model biological systems.     

银杏叶提取物对STZ和ISO协同诱发大鼠糖尿病心肌病的治疗作用

目的: 探讨银杏叶提取物(GBE) 对链脲佐菌素（STZ）和盐酸异丙肾上腺素(ISO)协同诱发大鼠糖尿病心肌病(DCM)的治疗作用。方法： 20只雄性Wistar大鼠随机分为正常对照组、模型组、阳性对照组和治疗组,每组5只。正常对照组大鼠不予处理,其他3组大鼠给予STZ和ISO造模,模型组大鼠给予生理盐水灌胃,阳性对照组和治疗组大鼠造膜后分别灌胃给予盐酸贝那普利和GBE,观察各组大鼠体质量、血糖水平、血清天冬氨酸氨基转移酶（AST）、乳酸脱氢酶（LDH）、转化生长因子β1（TGF-β1）蛋白表达水平和心肌组织形态学的变化。结果：给药1和2周时,模型组大鼠体质量、血糖水平较正常对照组降低(P<0.05）,阳性对照组和治疗组大鼠体质量、血糖水平大鼠较模型组降低(P<0.05）。模型组大鼠AST、LDH和 TGF-β1水平较正常对照组降低（P<0.05）,阳性对照组和治疗组大鼠AST、LDH和 TGF-β1水平较模型组升高（P<0.05）。正常对照组大鼠心肌无细胞肿胀;模型组大鼠心肌细胞出现界限清晰、多发散在坏死灶,坏死灶内有旺盛的成纤维细胞增生,并可见一定量的胶原纤维;治疗组大鼠心肌细胞坏死病灶面积减小,纤维化程度减轻。结论：GBE可以缓解STZ和ISO协同诱导的大鼠心肌损害。