Contractile force and resting tension in the presence of halothane and increased extracellular potassium or decreased extracellular pH in isolated guinea pig atria

To gain a better understanding of the direct actions of halothane on myocardial function in ischaemia, we studied the effects of increasing extracellular potassium concentration and decreasing extracellular pH (acidosis), alone or in combination with halothane, on the contractile force and resting tension in isolated atria. Guinea pig left atria were superfused with Tyrode’s solution and stimulated at 1 Hz. Isometric contractile force and resting tension were measured using a force displacement transducer. Perfusate potassium concentrations were increased from 5.4 mmol · L⁻¹ to either 8.1 mmol · L⁻¹ or 10.8 mmol · L⁻¹ by adding KCl to the standard Tyrode’s solution, and its pH was decreased from 7.4 to either 7.0 or 6.5 by decreasing bicarbonate. In standard Tyrode’s solution (potassium 5.4 mmol · L⁻¹, pH 7.4), halothane 0.5–2% reduced contractile force in a dose-dependent manner (P < 0.05); the effective concentration of halothane for 50% inhibition of contractile force (IC₅₀) was 1.3%. Both increasing extracellular potassium and decreasing extracellular pH decreased the contractile force in a potassium-or pH-dependent fashion. The negative inotropism of halothane (1%) was not altered by increasing potassium concentrations, whereas 1% halothane caused a greater decrease in contractile force at pH 6.5 than at pH 7.4. Halothane (1%) enhanced the acidosis (pH 6.5)-induced increases in resting tension. Arrhythmias were produced in one of eight preparations during acidosis, while four of eight preparations demonstrated arrhythmias during acidosis in the presence of halothane. These data suggest that acidosis and halothane may have a synergistic interaction on the contractile force and resting tension of the atria. The increase in resting tension observed during acidosis/ halothane conditions suggests than an increase in cytosolic calcium is associated with these synergistic interactions between acidosis and halothane. Pour mieux comprendre l’action direct de l’halothane sur la fonction myocardique pendant l’ischémie, nous avons étudié les effets de l’augmentation du potassium extracellulaire et de la diminution du pH extracellulaire (acidose), seuls ou en association avec l’halothane, sur la force contractile et la tension de repos d’oreillettes isolées. Des oreillettes gauches de cobaye furent perfusées avec une solution de Tyrode et stimulées à 1 Hz. La force contractile isométrique et la tension de repos ont été mesurées avec un transducteur de force de déplacement. Les concentrations de potassium perfusées ont été augmentées de 5,4 mmol · L⁻¹ à 8,1 mmol · L⁻¹ ou à 10,8 mmol · L⁻¹ par l’ajout de KCl à la solution standard de Tyrode, et son pH abaissé de 7,4 à 7,0 ou 6,5 par baisse des bicarbonates. Avec la solution standard de Tyrode (potassium 5,4 mmol · L⁻¹, pH 7,4), l’halothane (0.5–2%) diminue la force contractile proportionnellement à la dose (P < 0,05); la concentration efficace d’halothane requise pour produire une inhibition de 50% de la force contractile (IC_5O) a été de 1,3%. L’augmentation du potassium extracellulaire et la diminution du pH extracellulaire réduisent toutes les deux la force contractile proportionnellement au potassium ou au pH. L’inotropisme négatif de l’halothane (1%) n’est pas modifié par l’augmentation de la concentration de potassium alors que l’halothane produit une diminution plus importante de la force contractile à un pH de 6,5 que de 7,4. L’halothane (1%) exagère l’augmentation de la tension de repos induite par l’acidose (pH 6,5). Des arrythmies sont apparues sur une des huit préparations pendant l’acidose en présence d’halothane. Ces données suggèrent que l’acidose et l’halothane pourraient avoir une activité synergique sur le force contractile et la tension de repos des oreillettes. L’augmentation de la tension de repos observée pendant l’acidose combinée à l’halothane suggère l’association d’une augmentation du calcium cytosolique avec des interactions synergiques entre l’acidose et l’halothane.     

宫内节育器与兔子宫内膜生成内皮素的研究

自制金属单环放入兔左侧子宫角腔内,有明显抗生育效果,此为动物模型。选10只成年雌兔分为二组,将节育环放入每只兔左侧子宫角腔内,右侧为对照。一个月,三个月取子宫内膜,进行形态学观察,内皮素免疫组化定位及内膜组织中内皮素含量的测定。结果显示:内膜形态无明显改变,只在少数局部淋巴细胞略多。内皮素免疫组化定位显示左侧子宫角阳性反应比右侧强,一个月和三个月结果相似。放射免疫测定的内膜组织中内皮素含量左侧明显高于右侧。揭示金属单环引起内膜组织生成内皮素增加。     

If current mediatesβ-adrenergic enhancement of heart rate but not contractility in vivo

Background: The hyperpolarization-activated I_f current in the sinoatrial (SA) node participates in the spontaneous diastolic depolarization responsible for pacemaking function. Both sympathetic and parasympathetic control of heart rate is thought to involve modulation of I_f. This study tested whether -adrenoceptor activation of heart rate, but not contractile state, could be reduced by blockade of I_f channels in the intact, anesthetized pig.Methods: Both isopterenol (ISO, 0.1 g/kg/min i.v. for 5 min) and norepinephrine (NE, 0.3 g/kg/min i.v. for 5 min) were used sequentially to activate -adrenoceptors in five metomidathydrochloride-anesthetized pigs. Left ventricular pressure and dP/dt, aortic blood pressure and cardiac output were measured. I_f channels were then blocked selectively with 0.3 mg/kg i.v. zatebradine (ULFS49) and the test doses of ISO and NE were repeated. Following a further high dose (10 mg/kg, i.v.) of zatebradine, the test doses of ISO and NE were repeated once again.Results: Before I_f blockade, ISO and NE elicited reproducible increases in both heart rate and left ventricular dP/dt. Whereas NE caused an increase in both systolic (56%) and diastolic (53%) aortic pressure and a modest heart rate increase (22%), ISO caused a decrease in diastolic aortic pressure (–22%) and a marked increase in heart rate (81%). Low dose zatebradine reduced basal heart rate from 98±6 to 66±3 bpm, p<0.05; cardiac output fell by 20%, stroke volume increased by 18% and total peripheral resistance was unchanged. ISO after low-dose zatebradine still elicited marked increases in heart rate (66±3 to 105±5 bpm, p<0.05) and left ventricular dP/dt (774±94 to 3364±206 mmHg/s, p<0.05) and reduced aortic diastolic pressure (37 ±2 to 33±1 mmHg, p<0.05). NE after low-dose zatebradine increased heart rate (73±4 to 89±5 bpm, p<0.05), left ventricular dP/dt (810 ±95 to 3372±196 mmHg/s, p<0.05) and both systolic and diastolic aortic pressures. High dose zatebradine caused no further reduction in heart rate (77±4 vs 82±6 bpm, NS) but left ventricular dP/dt decreased (798 ±92 to 418±50 mmHg/s, p<0.05) as did both systolic and diastolic aortic pressures. Subsequent administration of ISO had no effect on heart rate but increased left ventricular dP/dt from 418±50 to 3468±256 mmHg/s (p<0.05) and systolic aortic pressure increased from 58±7 to 90 ±3 mmHg (p<0.05). NE administered after high dose zatebradine also increased left ventricular dP/dt (580±54 to 2608±182 mmHg/s, p<0.05) while heart rate fell (86±4 to 74±6 bpm, p<0.05). Both systolic and diastolic aortic pressures mereased substantially during the NE infusion after high dose zatebradine.Conclusion: Zatebradine dosedependently inhibits -adrenoceptormediated heart rate increases while leaving -adrenoceptor-mediated increases in myocardial contractile state intact. This observation can be explained by a selective blockade of the hyperpolarization-activated current I_f by low concentrations of the drug.     

Thiopentone inhibits beta-adrenergic responses in myocardial tissue

The purpose of this study was to determine the importance of inhibition of beta-adrenergic function in thiopentone-induced myocardial depression. Using an isolated, electrically stimulated rat left atria model, contractile dose-response curves to thiopentone (200 μM, 400 μM, 600 μM, 800 μM) were shifted to the right in preparations treated with 10^{− 3} M dibutyryl cyclic adenosine monophosphate (cAMP) compared with atria stimulated with 10^{− 6} M isoprenaline, demonstrating that inhibition of beta-adrenergic mechanisms by thiopentone is physiologically important. Depression by thiopentone was similar in atria treated with 10^{− 5} M forskolin compared with preparations stimulated with 10^{− 6} M isoprenaline, indicating that thiopentone does not block beta-adrenergic receptors. It is concluded that thiopentone depresses myocardial function by several mechanisms, one of which involves inhibition of the adenyl cyclase cascade. The adenyl cyclase enzyme is a likely site where thiopentone inhibits the system; however, other components of the cascade may also be involved. L’objectif de cette étude consiste à déterminer l’influence de l’inhibition de l’activité β-adrenergique sur la dépression myocardique induite par le thiopentone. A l’aide d’un modèle constitué d’une oreillette gauche de rat stimulée électriquement, la relation dose-effet du thiopentone sur la contractilité (200 μM, 400 μM, 600 μM, 800 μM) se déplace vers la droite dans des préparations traitées avec de l’adénosine monophosphorique cyclique (cAMP) 10^{− 3} M comparativement à des oreillettes stimulées avec de l’isoprénaline 10^{− 6} M, ce qui démontre que l’inhibition β-adrénergique provoquée par le thiopentone est physiologiquement importante. La dépression de l’oreillette provoquée par le thiopentone est identique à celle que produit la forskoline 10^{− 5} M comparativement à celle de l’isoprénaline 10^{− 6} M, ce qui indique que le thiopentone n’inhibe pas les récepteurs β-adrénergiques. Les auteurs concluent que le thiopentone déprime la fonction myocardique par plusieurs mécanismes qui impliquent l’inhibition de la cascade de l’adényl cyclase. L’inhibition du système se produit vraisemblablement au niveau de l’enzyme adényl cyclase; cependant, il est possible que d’autres éléments de la cascade de l’adényl cyclase soient impliqués.     

Decrease of some metabolic and physiologic effects of diazoxide by propranolol in rat

Summary Diazoxide significantly decreased the blood pressure and relaxed the uterine muscle in anaesthetized normotensive rats. A marked elevation of blood glucose followed the intravenous injection of diazoxide. The hyperglycemic and the uterine relaxing response could be significantly decreased by injection of propranolol prior to diazoxide. The hypotensive effect was not diminished by propranolol, however. In liver and uterus the content of cAMP was increased following diazoxide treatment in vivo. The rise in cAMP could be completely inhibited by propranolol, indicating a -receptor stimulation being the cause of the cAMP elevation.     

Electron microscopy and X-ray microanalyses of uterine epithelium from lead-injected mice in an experimental delay of implantation

Mice in experimental delay of implantation were injected intravenously with 75 g · g^–1 body weight of lead chloride, corresponding to a dose of lead of about 56 g · g^–1 body weight. Delay of implantation was obtained by ovariectomy 3 days after mating followed by a depot dose of progesterone every fifth day. Electron microscopy showed that the uterine lumen, which was closed in control mice, was opened in lead-injected mice. This morphology suggested that lead caused an increase in uterine secretion. X-ray microanalysis of pyroantimonate precipitates in the uterine epithelium of injected mice demonstrated lead in the precipitates, suggesting that lead could have a direct effect on the function of the uterine epithelium and that lead also could be secreted into the uterine lumen and affect the blastocysts.     

Succinylcholine does not worsen bupivacaine-induced cardiotoxicity in pentobarbital-anaesthetized dogs

The intravascular injection of a large dose of bupivacaine induces electrophysiological cardiac impairment, mainly by slowing ventricular conduction velocity, and haemodynamic depression, by a decrease in myocardial contractility. When cardiotoxicity occurs, succinylcholine rapidly stops convulsions. However, the possible interactions between bupivacaine and succinylcholine on cardiac electrophysiology and haemodynamic status have never been investigated. Thus, we used an experimental electrophysiological model involving closed-chest dogs. Three groups (n = 6) of pentobarbital-anaesthetized dogs were given 0.2 mg.kg-1 atropine iv. Dogs in Group 1 were given saline. The others received 4 mg.kg-1 bupivacaine iv over ten seconds. Dogs in Group 2 were then given saline and those in Group 3 were then given 2 mg.kg-1 succinylcholine iv from one to two minutes after the administration of bupivacaine. The following electrophysiological variables were measured: heart rate represented by RR interval (RR), PR, atria-His (AH), and His-ventricle (HV) intervals, QRS duration, and QT interval corrected for heart rate (QTc). The following haemodynamic variables were measured: mean aortic pressure (MAoP), the peak of the first derivative of left ventricular pressure (LV dP/dt max), and LV end diastolic pressure (LVEDP). Comparison between Groups 1 and 2 showed that bupivacaine induced more than 100% HV interval lengthening and QRS widening (P less than 0.01), prolonged QTc interval by more than 25% (P less than 0.01), and decreased LV dP/dt max by more than 50% (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

应用B超与子宫内膜病理检查联合诊断异常子宫出血232例分析

目的探索子宫异常出血症的B超声象与子宫内膜病理检查的关系.方法对232例子宫异常出血患者采用B超检查后做子宫内膜活组织病理检查,对B超显示子宫内膜增厚≥5mm或者有异常回声者作观察组,B超正常者为对照组.结果观察组190例中病理检查显示正常子宫内膜21例(11.05%),异常子宫内膜169例(88.95%),其中不全流产33例、子宫内膜炎12例、子宫内膜增生过长及分泌不良98例、子宫内膜息肉及粘膜下肌瘤15例、子宫内膜恶性病变11例;对照组42例中有4例(9.53%)为不全流产外,其余无病理征.结论先采用B超探查子宫内膜,对有异常声象作诊括术进行病理检查是诊断子宫异常出血症较为方便、简捷、有效的方法.     

子宫腺瘤样瘤临床病理分析

目的 探讨子宫腺瘤样瘤的组织发生、临床病理特征及鉴别诊断。方法 对ll例子宫腺瘤样瘤的资料，进行综合分析，光镜观察。其中6例进行免疫组化标记。结果 年龄2l—58岁，临床表现无特征性，肿瘤好发子宫角、宫底处。光镜下表现为上皮样细胞形成腺样、腔隙、条索样结构，有些上皮样细胞可呈空泡状、印戒样。大多伴有平滑肌瘤或平滑肌增生。免疫组化：CK、EMA、VIM、Calretinin均阳性表达，而FⅦ因子相关抗原、CEA均阴性。结论 子宫腺瘤样瘤是一种良性病变，符合间皮来源，尤其注意的是：此瘤出现以空泡、印戒样细胞为主时，易误诊为腺癌或印戒细胞癌，结合免疫标记，可鉴别之。     

ET—1、ETA—R、c—fos原癌原因mRNA在子宫肌瘤中的表达

目的 :探讨ET 1及ETA R表达在子宫肌瘤发生中的病理生理作用及其与肌瘤中c fos原癌基因之间的关系。方法 :应用半定量RT PCR方法检测 30例子宫肌瘤组织及邻近正常子宫肌组织中ET 1、ETA R、c fosmRNA的表达强度 ,对照其差异。结果 :( 1)子宫肌瘤组织中ET 1mRNA的表达强度 ( 2 .717± 0 .5 2 0 )与正常子宫肌组织 ( 2 .4 83± 0 .62 3)差异有显著性 (P <0 .0 5 ) ;ETA RmRNA在子宫肌瘤组织中表达为 2 .2 17± 0 .4 68,明显高于正常子宫肌组织的 1.617± 0 .4 86(P <0 .0 0 1) ;c fosmRNA在子宫肌瘤组织中表达为 4 .90 0± 0 .4 0 3,也明显高于正常子宫肌组织的 4 .183± 0 .5 94 ,(P <0 .0 0 1) ;( 2 )相关分析表明 :肌瘤组织中ETA RmRNA与c fosmRNA之间呈正相关 ,而ET 1mRNA与ETA RmRNA、c fosmRNA之间无相关性。结论 :子宫肌瘤组织中ETA R的表达上调对子宫肌瘤细胞的分裂增殖起促进作用 ,ET 1/ETA R系统可能是子宫肌瘤发生发展的机理之一