HPLC法同时测定盐酸异丙肾上腺素注射液和盐酸肾上腺素注射液的含量及有关物质

目的:建立测定盐酸异丙肾上腺素注射液和盐酸肾上腺素注射液的含量及有关物质的方法。方法:采用高效液相色谱法,色谱柱:Welch Materials C18色谱柱(4.6mm×150mm,5μm);流动相:甲醇-乙腈-庚烷磺酸钠溶液(1:1:8);检测波长:280nm;流速:2.0ml·min-1;柱温:30℃。结果:盐酸异丙肾上腺素在10～40μg.ml-1质量浓度范围内与峰面积呈良好的线性关系,r=0.9999;高、中、低3种浓度的平均回收率为100.5%,RSD为0.76%(n=9)。盐酸异丙肾上腺素的最小检测限为40.66ng·ml-1。盐酸肾上腺素在60～240μg·ml-1质量浓度范围内与峰面积呈良好的线性关系,r=0.9996;高、中、低3种浓度的平均回收率为100.2%,RSD为0.60%(n=9)。盐酸肾上腺素的最小检测限为44.12ng·ml-1。结论:该法简便、快速、准确、灵敏度高,重现性好,适用于盐酸异丙肾上腺素注射液和盐酸肾上腺素注射液的含量测定,也可用于有关物质检查。     

王不留行总黄酮对离体蛙心心肌收缩力和心率的影响

目的: 探讨王不留行总黄酮对离体蛙心的影响及可能的作用机制。方法: 采用斯氏蛙心灌流法制备离体蛙心标本,待离体蛙心收缩力稳定后,分别加入不同浓度的王不留行总黄酮、阿托品、盐酸异丙肾上腺素,观察这些药物对离体蛙心收缩活动的影响。结果: 总黄酮在0.02~0.10 mg·mL^-1范围内,随着王不留行总黄酮浓度的增大,离体蛙心心肌平均收缩力与给药前相比较明显减小(P<0.05或P<0.01);心率与给药前相比较,仅0.08 mg·mL^-1和0.10 mg·mL^-1剂量组与给药前比较减慢差异明显(P<0.05或P<0.01);心肌最大收缩力与给药前相比较,除0.04 mg·mL^-1剂量组外,其他4组与给药前比较均有明显抑制作用(P<0.01)。随着细胞外钙离子浓度的逐渐增大,王不留行总黄酮对蛙心心肌平均收缩力的抑制率逐渐增大(P<0.05或P<0.01),加入阿托品和盐酸异丙肾上腺素后提取液对离体蛙心的抑制作用有所降低。结论: 王不留行总黄酮对离体蛙心活动有一定的抑制作用,作用机制可能与钙离子通道有关,与心肌细胞膜上受体关系有待进一步研究。     

胍丁胺对异丙肾上腺素诱发人心房纤维迟后除极的影响(英文)

用标准微电极技术研究胍丁胺对异丙肾上腺素 ( Iso)诱发人心房纤维迟后除极的影响 .结果如下 :( 1 )胍丁胺 ( 1 - 1 0 mmol· L-1)以浓度依赖地方式明显抑制 Iso( 2 0 nmol· L-1)诱发人心房纤维的迟后除极 ;( 2 )预先应用咪唑啉受体和 α2 肾上腺素受体拮抗剂咪唑克生 ( 0 .1 mmol· L-1)可阻断胍丁胺 ( 1 0 mmol· L-1)对 Iso( 2 0 nmol· L-1)诱发迟后除极的抑制作用 ;( 3)预先应用一氧化氮合酶抑制剂硝基 - L-精氨酸甲酯 ( 0 .5mmol· L-1) ,不影响胍丁胺 ( 1 0 mmol· L-1)对 Iso( 2 0 nmol· L-1)诱发迟后除极的抑制作用 .结果表明 ,胍丁胺对 Iso诱发人心房纤维迟后除极的抑制作用可能是由于咪唑啉受体和 α2 肾上腺素受体介导钙内流减少所致 .     

Dyssynchrony of segment shortening in the anterior wall of the feline left ventricle

Non-uniformity of regional contraction may be both spatial and temporal. This study was undertaken to deal with the temporal aspects of shortening and to quantify non-uniformity with regard to timing. Nine cats were anaesthetized and artificially ventilated. Two pairs of ultrasonic crystals were situated in the anterior midwall of the left ventricle to measure regional shortening. One pair, longitudinal segment, was oriented to align with midwall fibres. The other pair, transverse segment, was placed perpendicular to the first one. Registrations in control state, during caval occlusion, and during aortic constriction were carried out with and without isoprenaline infusion. Cyclic events were analysed in terms of phase angle, 0–2π representing one heart cycle. Transverse segments showed marked shift of duration of shortening, from 1.19π± 0.06π (meanæM) in the control state to 0.40π± 0.14π during caval occlusion with isoprenaline infusion. Duration of shortening of longitudinal segments showed less prominent shift with mean values between 1.38π and 1.11π. Regional uniformity of timing, expressed as synchronization index, varied markedly with interventions (P < 0.0005). Dyssynchrony was most prominent during caval occlusion with mean values less than 0.6. A simple model of force generation for the two segments visualizes that segment shortening of the transverse segment is of shorter duration than the longitudinal segment and a common mechanism for temporal and spatial non-uniformity within a region could be elaborated. This study quantifies both the time course of shortening and temporal non-uniformity of two cross-oriented segments within the same myocardial region.     

Mechanism underlying the reduced positive inotropic effects of the phosphodiesterase III inhibitors pimobendan,adibendan and saterinone in failing as compared to nonfailing human cardiac muscle preparations

Summary The present study was performed to compare the effects of the new positive inotropic phosphodiesterase III inhibitors pimobendan, adibendan, and saterinone on the isometric force of contraction in electrically driven ventricular trabeculae carneae isolated from explanted failing (end-stage myocardial failure) with those from nonfailing (prospective organ donors) human hearts. In preparations from nonfailing hearts the phosphodiesterase inhibitors, as well as the a-adrenoceptor agonist isoprenaline, the cardiac glycoside dihydroouabain, and calcium, which were studied for comparison, revealed pronounced positive inotropic effects. The maximal effects of pimobendan, adibendan, and saterinone amounted to 56%, 36% and 45%, respectively, of the maximal effect of calcium. In contrast, in preparations from failing hearts the phosphodiesterase III inhibitors failed to significantly increase the force of contraction and the effect of isoprenaline was markedly reduced. The effects of dihydroouabain and calcium were almost unaltered. The diminished effects of isoprenaline were restored by the concomitant application of phosphodiesterase inhibitors.To elucidate the underlying mechanism of the lack of effect of the phosphodiesterase III inhibitors in the failing heart we also investigated the inhibitory effects of these compounds on the activities of the phosphodiesterase isoenzymes I–III separated by DEAE-cellulose chromatography from both kinds of myocardial tissue. Furthermore, the effects of pimobendan and isoprenaline on the content of cyclic adenosine monophosphate (determined by radioimmunoassays) of intact contracting trabeculae were studied. The lack of effect of the phosphodiesterase inhibitors in failing human hearts could not be explained by an altered phosphodiesterase inhibition, since the properties of the phosphodiesterase isoenzymes I–III and also the inhibitory effects of the phosphodiesterase inhibitors on these isoenzymes did not differ between failing and nonfailing human myocardial tissue. Instead, it may be due to a diminished formation of cyclic adenosine monophosphate in failing hearts, presumably caused mainly by a defect in receptor-adenylate cyclase coupling at least in idiopathic dilated cardiomyopathy. Both the basal and the pimobendan-stimulated or isoprenaline-stimulated contents of cyclic adenosine monophosphate of intact contracting trabeculae from failing hearts were decreased compared with the levels in nonfailing hearts. However, under the combined action of isoprenaline and pimobendan the cyclic adenosine monophosphate level reached values as high as with each compound alone in nonfailing preparations, and in addition the positive inotropic effect of isoprenaline was restored.These findings may have important clinical implications. Along with the elevated levels of circulating catecholamines the positive inotropic effects of the phosphodiesterase inhibitors may be maintained in patients with heart failure. Furthermore, the concomitant application of a -adrenoceptor agonist and a phosphodiesterase inhibitor might be beneficial in terminal heart failure refractory to conventional therapeutic regimens.Some of the results reported in this paper have already been presented in abstract form at the 61 st Session of the American Heart Association, Washington, DC, Nov. 1988 (von der Leyen et al., Circulation 78 (Suppl II): 11-360, 1988), at the Fall Meeting of the German Society of Pharmacology and Toxicology, Sept. 1988 (Schmitz et al., Naunyn-Schmiedeberg's Arch Pharmacol 338 (Suppl): R 16, 1988), at the 30th Spring Meeting of the German Society of Pharmacology and Toxicology, March 1989 (Meyer et al., Naunyn-Schmiedeberg's Arch Pharmacol 339 (Suppl): R 53, 1989), and at the XIII Congress of the International Society For Heart Research, Ann Arbor, MI, May 1989 (Meyer et al., J Mol Cell Cardiol 21 (Suppl 11): S. 50, 1989) mis|Send offprint requests to Wilfried Meyer at the above address     

Effects of carbachol on isoprenaline evoked amylase release from the rabbit parotid gland in vitro

Amylase secretion from dispersed lobules of the parotid gland of the rabbit was studied in response to isoprenaline (10^-8–10^-8M) and to carbachol (10^-8–10^-5M). The effects of each agent were investigated alone and in combination at certain concentrations. Isoprenaline produced a dose-related amylase secretion with an average maximum of 688 units/100 mg, at 10^- 5M. The amylase secretion produced by submaximal concentrations of isoprenaline could be further increased by carbachol, already in low concentrations (10^-8–10^-7M), that were subthreshold for amylase secretion. This potentiating effect was seen not only as a larger secretion but also as a greater depletion of amylase from the tissue. In contrast to what is known from experiments in vivo, carbachol in a high concentration (10^-5M), by activating muscarinic receptors only, released amylase to the same extent as that released by isoprenaline. This concentration of carbachol regularly decreased the amylase secretion evoked by isoprenaline, and may be regarded as unphysiologically high. The increase in isoprenaline evoked amylase secretion, brought about by carbachol in lower concentrations, may be due to an improved transport of amylase, because of secretion of fluid, but could also be caused by augmentation of the β-adrenoceptor mediated effects.     

Effect of Bordetella pertussis Vaccination in Mice and the Isolated Tracheal Response to Isoprenaline

The administration of Bordetella pertussis vaccine to mice has been associated with the development of an impaired beta-adrenoceptor responsiveness and in many respects has resembled human asthma. Trachea (n = 12) were isolated from Swiss-Webster mice 5 days following the intraperitoneal administration of 2 x 10(9) B. pertussis organisms. The tracheal smooth muscle response to carbachol was measured and compared with that found in trachea from unvaccinated mice (n = 15). The contractile response was similar in both groups. The tracheal smooth muscle relaxant effects of isoproterenol were measured in these two groups. The EC50 value for isoprenaline (6.5 x 10(-7) M) in trachea from B. pertussis treated mice was significantly (P < 0.05) greater than that noted in the control animals (2.3 x 10(-7) M). These studies demonstrated that in tracheal smooth muscle isolated from B. pertussis vaccinated mice, the relaxant effects of isoprenaline are impaired.     

Return of β-adrenergic sensitivity in a patient with insulinoma after removal of the tumour

β-Adrenergic sensitivity and counterregulatory hormone and symptomatic responses to hypoglycaemia were studied in a 22-year-old man before and 3 and 34 weeks after removal of an insulinoma. The β-adrenergic sensitivity was measured by the effect of an isoprenaline infusion on the heart rate, and the dose needed to increase the heart rate by 25 beats min⁻¹ (I₂₅) calculated from regression lines. The glucose thresholds for the hormonal responses and symptoms were studied during a gradual fall in plasma glucose using a hypoglycaemic clamp technique. As compared with preoperative values, β-adrenergic sensitivity was unchanged 3 weeks after surgery, but showed a marked improvement after 34 weeks, the I₂₅ (in μg isoprenaline) being 0.96, 0.86, and 0.56, respectively. The hormone responses to hypoglycaemia were earlier, but with no improvement in symptom generation at 3 weeks. After 34 weeks, the thresholds for both hormone release and symptom generation occurred at a plasma glucose approximately 1 mmol l⁻¹ higher than before surgery. Thus, in our patient, there was a marked improvement in β-adrenergic sensitivity, an earlier release of counterregulatory hormones, and an earlier recognition of hypoglycaemic symptoms after surgery. However, the restoration of these responses took more than 3 weeks. © 1997 John Wiley & Sons, Ltd.     

酸枣仁总皂甙对小鼠缺氧的保护作用和体外对家兔血小板聚集及产生血栓素B_2的影响

酸枣仁总皂甙(ZS 100mg/kg IP)对小鼠常压缺氧和异丙肾上腺素加重的缺氧及亚硝酸钠所致的携氧障碍均能显著延长存活时间。用比浊法和放射免疫测定法研究ZS对家兔凝血酶诱导的血小板聚集和产生血栓素B_2(TXB_2)的影响。ZS(25-660mg/L)显著抑制血小板聚集和TXB_2的产生。上述结果提示:ZS对缺氧的保护作用与抗血小板聚集和减少TXB_2生成有关。