甘糖酯对豚鼠乳头状肌动作电位和收缩的抑制作用

目的：观察甘糖酯（PGMS）对豚鼠乳头状肌动作电位和收缩力的影响。方法：利用细胞内微电极技术记录豚鼠乳头状肌的块反应动作电位，慢反应动作电位及收缩力。结果：PGMS浓度依赖性地使FAP的动作电位时程缩短和FC减弱，但对静息电位和动作电位幅度及O期最大除极速率均无显影响。PGMS浓度依赖性地使BaCl2诱发的SAP的Vmax和APA降低，APD缩短，PGMS浓度依赖性的使异丙肾上腺素诱发的SAP的APA降低，APD缩短，FC减弱，提高细胞外Ca^2 浓度后，以上各项参数基本恢复正常。结论：PGMS对乳头状肌动作电位和收缩力的影响可能是选择性抑制慢内向电流。     

青滕碱对豚鼠心肌动作电位和收缩力的影响

青藤碱2.7μmol/L以上,呈浓度依赖性地降低豚鼠乳头肌收缩力,延长动作电位时程和有效不应期。小剂量时,青藤碱能降低动作电位0相上升最大速率;较大剂量时,动作电位幅度也降低。用TTX处理豚鼠乳头肌所致的慢反应电位,青藤碱能够抑制。此外,青藤碱能对抗乙酰胆碱缩短豚鼠左房肌动作电位时程的作用。结果提示:青藤碱对Na⁺,Ca²⁺和K⁺的跨膜转运均有抑制作用。     

白细胞介素2对大鼠心肌主动及被动电特性的影响

目的　了解白细胞介素对心脏电特性的影响。方法　在大鼠右心室乳头肌标本上,用玻璃微电极技术,观察白细胞介素2 (IL-2 )对心肌动作电位和被动电特性的影响。结果　IL-2使心肌动作电位时程(APD₅₀和APD₈₀)缩短,对静息电位、动作电位幅度和0期去极化最大速度无显著作用;IL-2引起乳头肌心肌细胞空间常数和时间常数增加,细胞内阻降低。结论　IL-2可改变大鼠心肌的主、被动电特性     

白细胞介素2对大鼠心肌主动及被动电特性的影响

目的 了解白细胞介素对心脏电特性的影响。方法 在大鼠右心室乳头肌标本上，用玻璃微电极技术，观察白细胞介素2(IL—2)对心肌动作电位和被动电特性的影响。结果 IL-2使心肌动作电位时程(AD50和APD80)缩短，对静息电位、动作电位幅度和0期去极化最大速度无显著作用；IL—2引起乳头肌心肌细胞空间常数和时间常数增加，细胞内阻降低。结论 IL-2可改变大鼠心肌的主、被动电特性。     

甲氧普胺对豚鼠缺氧与非缺氧心肌动作电位和收缩力的影响

甲氧普胺10μmol/L使乳头状肌动作电位0相上升最大速率(Vmax)降低,100μmol/L并使收缩力(FC)低,300μmol/L时动作电位时程(APD_(20),APD_(90))缩短,30μmol/L使缺氧心肌动作电位的Vmax降低,APD_(20)缩短。     

抗心律失常药 恩卡胺(Encainide)

异名 Enkaid 化学名 (±)-2′-[2-(1-甲基-2-哌啶基)乙基]-对甲氧苯甲酰基苯胺盐酸盐药效分类抗心律失常药开发单位 (美)Bristol-Myers Co 上市厂商 (美)Bristol-Myers Co 1987年首次上市药理本品属IC类抗心律失常新药。通过阻断快反应Na~+内流而降低各种动物标本动作电位去极化时的最大上升速度(V_(max)),该作用呈剂量依赖性。本品是I类抗心律失常药物中降低V_(max)及延长速度依赖的动作电位回复时间最大的药物之一,对快Na~+流的阻断作用与氟卡胺或劳卡胺类似。本品还能减小离体组织标本动作电位幅     

布比卡因的临床应用

布比卡因 (ｂｕｐｉｖａｃａｉｎｅ ,Ｂｕｐ)是临床上常用的酰胺类局麻药 ,具有麻醉效能强、作用时间长、感觉及运动阻滞分离明显等特点[1 ] 。研究表明 ,其对心脏Ｎａ 和Ｃａ2 通道有较强的抑制作用 ,能降低心肌细胞动作电位幅度 ,缩短动作电位时程 ,降低心肌慢反应动作电位幅度 ,减慢窦性心率 ,延长心电图ＰＲ和Ｑ Ｔ间期 ,继而出现房室传导阻滞、二联律、三联律、室性早搏和室性心动过速 ,严重时出现明显的心肌细胞毒性作用[2 ] 。临床应用时 ,应特别注意。现将其近年来临床新进展综述如下。1　术后镇痛1.1　单用Ｂｕｐ术后镇痛　硬膜…     

当归A_3部位对心肌生理特性和动作电位的影响

目的　研究A3 部位对离体心肌生理特性和心室乳头肌动作电位的影响。方法　采用常规离体器官实验法记录右房自搏频率、心肌收缩力和功能性不应期 ;采用标准细胞内微电极技术记录动作电位 (AP)。结果　A3 部位 (10～ 16 0mg·L-1)能显著抑制右心房的自搏频率 ,16 0mg·L-1时可使右心房停搏 ;它剂量依赖性地降低左心房的收缩力 ,IC50 为5 2 3mg·L-1;它还明显延长功能性不应期 (FRP) ,10 0mg·L-1时 ,使FRP从给药前的 10 6ms延长至 130ms ;A3 部位剂量依赖性地降低动作电位振幅 (APA) ,缩短复极 2 0 %时程 (APD2 0 )和复极 90 %时程 (APD90 ) ,对静息电位 (RP)无影响。结论　当归A3 部位对心肌生理特性和动作电位的作用可能与其阻Ca2 + 、Na+ 内流和促K+ 外流有关     

IHC-66对犬心室肌和浦顷野纤维的电生理作用

目的：观察IHC-66(3,6-dimethylamino-dibenzopyriodonium of ferric EDTA) 对离体犬心室肌与浦顷野纤维的电生理影响。 方法：采用心肌细胞内玻璃微电极技术。 结果：IHC-66可缩短犬心室肌动作电位复极20%和50%的时程,降低动作电位零相最大除极速率、缩短浦顷野纤维APD₅₀。 在较高浓度时, IHC-66还降低犬心室肌与浦顷野纤维动作电位振幅和延长动作电位APD₉₀。 结论：IHC-66对犬心室肌细胞APD₂₀和Vmax的抑制作用明显较浦顷野纤维强,对浦顷野纤维动作电位Vmax呈现频率依赖性抑制作用。     

磷酸羟基喹哌对豚鼠右室乳头状肌动作电位和收缩力的影响

本文采用常规微电极技术,研究了HPQP对豚鼠乳头状肌电和机械活动的影响。HPQP在10μmol/L以上是浓度依赖性地抑制收缩力,延长动作电位时程和有效不应期,低浓度时仅抑制V_(max),浓度在100μmol/L以上时可使动作电位幅度降低。在30μmol/L时能对抗乙酰胆碱缩短左房肌动作电位时程的作用。HPQP 100μmol/L能对抗哇巴因诱发的后振荡电位。结果提示:HPQP能非特异性地抑制Na~+,K~+和Ca~(2+)的跨膜转运。     

Inhibition of rat heart mitochondrial respiration by cadmium chloride

Mitochondria were isolated from hearts obtained from adult male Sprague-Dawley rats by two-part differential centrifugation of heart homogenates. Time-dependent (0-120 sec) and concentration-dependent (0-10 microM CdCl2) effects of cadmium on pyruvate-malate-supported state 3 and state 4 respiration were measured in a constant temperature reaction chamber at 37 degrees C, according to established procedures. The ID50 for cadmium chloride on state 3 respiration was determined to be 4.2 microM. The inhibition produced by cadmium chloride in heart mitochondria was compared, using identical procedures, to the effects induced by two compounds, sodium atractyloside and potassium cyanide, which are known to alter mitochondrial respiration at specific sites. The calculated ID50 values for these agents in heart mitochondria were 1.8 and 16 microM, respectively. The concentration-dependent inhibition of mitochondrial respiration induced by either cadmium chloride or potassium cyanide was maintained in the presence of 50 microM carbonyl cyanide m-chlorophenylhydrazone (CCCP), a known uncoupling agent. In contrast, sodium atractyloside did not block the uncoupling effect of 50 microM CCCP. In addition cadmium chloride was also shown to inhibit CCCP-uncoupled mitochondrial respiration. The cadmium-induced inhibition of mitochondrial respiration was reversed partially by cysteine and completely by 2,3-dimercaptopropanol. The results of the present study indicate that, at all concentrations, cadmium chloride acted solely as an inhibitor of rat heart pyruvate-malate-supported mitochondrial respiration. These findings suggest a possible mechanism for the reported disturbances in myocardial metabolism and function that occur in conjunction with acute and chronic cadmium exposure in humans and experimental animals.     

Arsenic-cadmium interaction in rats: toxic effects in the heart and tissue metal shifts

Previously, we had shown that arsenic interacts with cadmium in rats; our results showed that the toxicity of a mixture of arsenic + cadmium cannot be predicted by the toxic mechanisms of the individual components. In this paper, we present further evidence about the interaction of arsenic and cadmium in rats. The results were: arsenic modified the 24 h-LD50 value of cadmium more clearly than cadmium did with the one of arsenic; based on the LD50 values, the mixtures we studied were more toxic than either metal alone. With single doses (As 10 mg/kg, Cd 2.6 mg/kg, and As 10 mg/kg + Cd 2.6 mg/kg) the mixture As + Cd was more toxic than each metal. At these doses, cadmium significantly induces the levels of glutathione, metallothionein, and lipid peroxidation in heart tissue, as compared to a saline group of rats. Arsenic incremented glutathione and lipid peroxidation at higher values than those obtained with cadmium. The mixture of As + Cd behaved as arsenic in the induction of lipid peroxidation and glutathione and like cadmium in metallothionein induction. Finally, rats treated with As + Cd had less Cd in liver than animals treated only with cadmium, and more As in heart tissue than rats treated only with arsenic. Our results give further evidence about the arsenic-cadmium interaction in rats, demonstrate the utility of employing different biomarkers in the study of chemical mixtures and indicate that heart tissue is affected not only by the mixture of As + Cd, but also by either metal alone.     

Cadmium Induced Changes in Gluconeogenic Enzymes in Rat Kidney and Liver

Male Sprague-Dawley rats were administered cadmium chloride 0, 50, 100, 150 and 200 ppm for 30 days. At the end of the treatments, the body weight gains, serum glucose, serum protein, serum glutamic oxalacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) were determined. Renal and hepatic key gluconeogenic enzymes; viz., pryuvate carboxylase, phosphoenol pyruvate carboxykinase, fructose-1, 6-diphosphatase and glucose-6-phosphatase were also determined. A significant decrease in body weight gain in rats treated with cadmium was observed. The serum glucose and protein levels were increased in rats receiving cadmium through feed. All four key gluconeogenic enzymes were increased in both kidney and liver tissues of rats treated with cadmium. The present results indicate that cadmium may induce gluconeogenesis from non-carbohydrate sources.     

Evaluation of genotoxic damage of cadmium chloride in peripheral blood of suckling Wistar rats

The aim of this study was to evaluate possible genotoxic damage of cadmium chloride exposure in suckling rats by means of the comet assay and the in vivo micronucleus test of rat blood lymphocytes, because no information is available on the genotoxic effect of cadmium in rats at this early age. Pups were receiving cadmium (as CdCl(2).H(2)O) orally in fractions of 0.5 mg for 9 days, totalling 4.5 mg Cd kg(-1) body wt, or were given a single subcutaneous injection of 0.5 mg Cd kg(-1) body wt. Some pups in both exposed groups were receiving calcium supplement (CaHPO(4).2H(2)O) in feed to reduce the body load of cadmium. Control pups did not receive either cadmium or calcium supplement. Cadmium in the carcass and organs was measured by atomic absorption spectrometry. The results showed that the cadmium body burden was significantly lower when the animals were receiving calcium supplements along with oral cadmium. The results of the micronucleus and comet assays showed significant differences between the control and exposed groups, regardless of the route of cadmium administration. The only statistically significant difference between the two exposed groups (oral cadmium and oral cadmium + calcium supplements) was in the number of micronuclei. The results of the comet assay showed that tail length differed statistically only between the control and all exposed groups, regardless of the route of cadmium administration. It can be concluded that the applied cadmium doses caused detectable genome damage but it was lower in calcium-treated pups receiving cadmium orally.     

镉所致肾损害与脂质过氧化的实验

每天以２ｍｇ／ｋｇ氯化镉生理盐水溶液给大鼠腹腔注射１５天，结果显示：氯化镉可引起肾功能的改变和脂质过氧化指标ＭＤＡ的升高及ＳＯＤ的下降，说明镉可诱发肾脏的脂质过氧化。亚细胞组分分析表明镉诱导的脂质过氧化主要发生在线粒体及微粒体中。比较脂质过氧化与肾损害出现的时间，可见染镉动物肾皮质及亚细胞组分ＭＤＡ的升高及ＳＯＤ的下降的时间均晚于肾功能异常。可以认为肾脏脂质过氧化并非镉引起肾损害的直接原因     

Behavioral deficits due to prenatal exposure to cadmium chloride in CFY rat pups

The postnatal behavioral effects of 0.20, 0.62 and 2.0 mg/kg cadmium chloride administered to pregnant CFY rats on gestational days 7 through 15 were evaluated. Offspring were tested starting on postnatal day 23 on a rotorod for motor coordination, in an open field device for motor activity and emotionality, in a water-filled tube for stress responses, in the acquisition and extinction of an instrumental shock-escape response and in a social interaction situation. All behavioral measures showed significant alterations at the medium and high dose of cadmium exposure. The results suggest that doses of cadmium chloride that produce no overt toxicity in the dam can have long-lasting behavioral alterations in the offspring.     

Comparative effects of three chelating agents on distribution and excretion of cadmium in rats

Sodium N-benzyl-D-glucamine dithiocarbamate (NBG-DTC), which was newly synthesized, 2,3-dimercaptopropanol (BAL), and N-methyl-D-glucamine dithiocarbamate (NMG-DTC) were compared for their relative efficacies in the distribution and excretion of cadmium in rats exposed to cadmium. Rats were injected ip with 109CdCl2 (1 mg Cd and 10 microCi 109Cd/kg) and 3 days later, they were treated with the chelating agents (400 mumol/kg) every other day for 2 weeks. These chelating agents were effective in removing cadmium from the body without increasing the amount of cadmium in the kidney. After treatment with these chelating agents, cadmium was excreted mainly in the feces through the bile and the fecal excretion of cadmium by NBG-DTC was significantly larger than that by BAL or NMG-DTC. The hepatic cadmium content after treatment with NBG-DTC was much more decreased than that with BAL or NMG-DTC. The renal cadmium content was decreased only after treatment with NBG-DTC. These chelating agents did not result in the redistribution of cadmium to brain, testes, and heart. The growth of rats was little retarded by treatment with NBG-DTC and NMG-DTC, but was retarded by treatment with BAL. The treatment with NBG-DTC decreased the tissue amounts of Zn, Fe, and Mn to a small extent as compared with the treatment with cadmium alone. The results of this study reveal that the injection of NBG-DTC to rats pretreated with cadmium can more effectively remove cadmium from the body without the mobilization of cadmium to the kidney, the critical organ in cadmium toxicity, and without redistribution of cadmium to other tissues such as brain, testes, and heart, than injection of BAL and NMG-DTC.     

Sex-related effect of cadmium on hepatic cytochrome p-450, drug-metabolizing enzymes and 5-aminolevulinic acid synthetase and heme oxygenase in the rat

The effect of cadmium on hepatic cytochrome P-450 containing drugmetabolizing enzymes, δ-aminolevulinic acid synthetase (ALA synthetase) and heme oxygenase activity in both male and female rats was examined to define the nature of sex differences in response. In male rats injected i.p. with a single dose of cadmium chloride (1.25 mg Cd/kg body weight) there was a reciprocal relationship between the decrease of cytochrome P-450 levels and drug-metabolizing enzymes and the increase of heme oxygenase activity for up to 120 h. Hepatic ALA synthetase activity was initially decreased and returned to control levels at 24 h. In female rats, cadmium initially produced similar effects to those seen in male rats, but these were of shorter duration except for the increase of heme oxygenase activity. In addition, ALA synthetase activity was slightly increased at 24 h and 48 h.The results suggest that the sex differences in response reside mainly in the duration of the metal effect on these hepatic enzymes.     

Chelating-agent suppression of cadmium-induced hepatotoxicity

The administration of sodium N-methyl-N-dithiocarboxy-D-glucamine (NaG) at 500 mg/kg, i.p., or sodium calcium diethylenetriaminepentaacetic acid (DTPA) at 632.5 mg/kg, i.p., reduces the serum enzyme levels characteristic of hepatic damage following the intravenous administration of cadmium chloride (3.5 mg CdCl2.2.5H2O/kg). Some effect on serum enzyme levels was found even when the interval between administration of cadmium chloride and that of the antagonist was as great as 4 h. The enzymes examined included aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), alanine aminotransferase (SGPT), and alkaline phosphatase (AP). A histopathological examination of the livers of such animals also reveals the presence of a significant protective action.     

Cadmium toxicity in kidney cells. Resistance induced by short term pretreatment in vitro and in vivo

Epithelial cells from the kidney were freshly isolated from rats pretreated by daily subcutaneous doses of CdCl2 in vivo (0.5-2 mg Cd/kg X 5). Such cells were incubated in vitro in media with different concentrations of cadmium chloride (0-200 micrograms Cd/ml). There was no inhibition of cell growth in such cells. However, in cells isolated from non-treated rats, in vitro exposure to the same concentrations of CdCl2 caused a dose dependent decrease in viability. When cells, isolated from non-treated rats were pretreated in vitro with CdCl2 (10 micrograms/ml) and subsequently exposed to cadmium chloride (0-200 micrograms/ml), a protective effect was observed, which was similar to the one observed in cells isolated from animals pretreated with CdCl2. The concentration of metallothionein in the cells treated with cadmium was increased. A lower uptake of cadmium chloride, in vitro has been observed in kidney cells pretreated in vivo or in vitro compared to nonpretreated cells. Subcellular distribution studies indicate that Cd-distribution was similar in pretreated and non-pretreated cells, but concentrations were generally lower in the pretreated cells. The decreased uptake of Cd by pretreated kidney cells is a sign of Cd-interference with cellular function. These changes are suggested as a contributing mechanism to the prevention of acute toxic effects of cadmium on the kidney.