镉对豚鼠心脏的毒性影响

不同浓度的CdCl_2可使豚鼠右心室乳头肌毒性表现不同。2×10~(-5)M对豚鼠快反应APA及Vmax无显著影响。10~(-4)和5×10~(-4)M可抑制APA、Vmax,缩短APD抑制FC。而在慢反应实验中均呈抑制作用。实验说明低剂量cd使心肌细胞兴奋收缩脱耦联,大剂量对心肌有直接的毒性作用。     

巴马汀对离体乳头肌电生理特性的影响

巴马汀(Pal,50μmol/L)可使离体豚鼠右心室乳头肌的自律性降低、功能不应期(FRP)延长,但对兴奋性和收缩力无明显影响。Pal(10～100μmol/L)是浓度依赖性地延长动作电位时程(APD),其中APD_(90)延长比较显著。100μmol/L时,还使V_(max)降低。     

环维黄杨星D对豚鼠离体右心耳和乳头肌的作用

目的观察环维黄杨星D(CVB-D)对豚鼠离体右心耳、乳头肌的作用.方法制作豚鼠离体右心耳、乳头肌模型,观察不同浓度CVB-D对其收缩作用以及对乳头肌兴奋阈值的影响.结果CVB-D在(0.01～0.D×10.mol·L一的浓度下对右心耳的收缩性有降低作用,(0.3～D×10-5mol·L-1浓度下对右心耳收缩性有增强作用,该作用在1×10.mol·L一时最为明显,而对其自律性有浓度依赖性抑制作用;CVB-D对豚鼠乳头肌的收缩性总体有增强趋势,对其兴奋性则有明显的抑制作用,(0.3～1)×10-5 mol·L-1浓度范围内表现为波宽-阈值曲线右上移动.结论CVB-D对豚鼠右心耳增强收缩性,降低自律性以及增强乳头肌收缩性和降低兴奋性的作用与其浓度有关.     

小檗碱对豚鼠左心房和气管的作用

目的:观察小檗碱(berberine,Ber)对豚鼠左心房和气管的作用.方法:采用离体豚鼠左心房和气管条实验,比较Ber与吡那地尔(pinacidil,Pin)的作用.结果:Ber呈浓度依赖性的增强左房收缩张力,而Pin则浓度依赖性的减弱左房收缩张力.Ber使氨甲酰胆碱(carbachol,Car)抑制左房收缩的累积量效曲线平行右移,最大反应(Emax)基本不变,而Pin使Car量效曲线左移;当两药同时存在时,量效曲线同对照组基本相同.在豚鼠气管,Ber使乙酰胆碱(acetylcholine,ACh)累积量效曲线左移,而Pin则使其右移,Emax不压低,当两药同时存在时,量效曲线同对照组基本相同.结论:Ber对钾通道有阻滞作用.     

地高辛口服液对动物心肌收缩力的影响

目的考察地高辛口服液对动物心肌收缩力的影响。方法离体乳头肌法及在位心脏实验测定药物对乳头肌及心肌收缩力的影响。结果地高辛口服液使豚鼠离体乳头肌收缩振幅增加 5 0 %时的用药浓度为 8 91 3mmol/L ;地高辛口服液静脉给药 ,对戊巴比妥钠诱发家兔心力衰竭所致的心脏收缩幅度下降有显著的抑制作用 ;经口给药 0 5～ 2 0mg/kg,对麻醉家兔的心肌收缩有增强作用。结论地高辛口服液对豚鼠离体乳头肌及在位兔心均有明显的收缩作用。。     

氧化苦参碱的强心作用

用多种实验动物研究了氧化苦参碱的强心作用,结果表明:氧化苦参碱(05、5、50mol/L)能明显增加正常离体蟾蜍心肌收缩力、心输出量,强心同时不增加心率;显著增加戊巴比妥钠和低钙离体心衰模型的心肌收缩力、心输出量(P<005或P<001);50mmol/L可使心肌收缩力、心输出量完全恢复到心衰前水平,对心率无明显影响;能不同程度地加强离体豚鼠、大鼠、兔乳头肌的收缩力,均呈现良好的量效关系,对豚鼠乳头肌更为敏感;增加大鼠离体右心房心肌收缩力同时降低其自发收缩频率(P<001).     

2-[对-(二甲氨基)苯乙烯]氯化甲基吡啶对大鼠心电图、豚鼠左心房收缩及乳头肌动作电位的影响

2-[对-(二甲氨基)苯乙烯]氯化甲基吡啶(DSPM-Cl),是由氯取代2-[对-(二甲氨基)苯乙烯]碘化甲基吡啶(DSPM)上的碘而得。本文应用心电图、机械收缩描记方法及细胞内标准微电极技术,研究DSPM-Cl对大鼠心电图(ECG)、豚鼠心房肌量效曲线及对豚鼠乳头肌快反应动作电位(AP)、高钾除极慢反应动作电位(SAP)的影响。结果显示,DSPM-Cl(2mg·kg^-1)对大鼠有明显的负性频率、负性传导作用,分别使PP间期、PR间期延长达66.2%(P<0.01),17.0%(P<0.01),50μmol·L^-1能明显抑制左心房收缩力,非竟争性拮抗Iso及CaCl₂对豚鼠左心房的正性肌力作用,PD^2'分别为4.6,4.34,100μmol·L^-1DSPM-Cl延长动作电位时程APD₉₀,有效不应期(ERP),降低高钾除极豚鼠乳头肌0期最大上升速率Vmax,其作用与Ver相似,提示DSPM-Cl可能为钙拮抗剂。     

染料木素对离体豚鼠左室乳头肌收缩功能的影响

目的观察染料木素对离体豚鼠左室乳头肌收缩功能的影响,并探讨其作用机制。方法将离体豚鼠乳头肌置于装有KH液的灌流肌槽中,待平衡后,加入各种药物观察乳头肌收缩活动的变化。结果染料木素和异丙肾上腺素相似,可增强豚鼠左室乳头肌的收缩活动,染料木素(1、100μmol.L-1)的作用还具有明显的剂量依赖性。心得安(1μmol.L-1)和异搏定(0.5μmol.L-1)虽可明显阻断异丙肾上腺素(2μmol.L-1)的正性肌力作用,但对染料木素(100μmol.L-1)的心肌收缩增强效应无明显改变;同时发现染料木素(1、10μmol.L-1)对细胞外液Ca2+浓度升高而诱发的心肌收缩力增强也无明显影响。另外,它莫西芬(1μmol.L-1)可明显减弱染料木素的正性肌力作用,但正矾酸钠(1μmol.L-1)对其作用无明显影响。结论染料木素可增强心肌收缩活动,其作用与心肌细胞膜上的β肾上腺素能受体和钙通道激活以及酪氨酸激酶途径无关,可能与肌质网Ca2+的摄取和利用有关。     

广枣总黄酮对心肌细胞内游离钙浓度的影响

目的：研究广枣总黄酮（TFC）对心肌细胞内游离钙浓度的影响。方法：以大白鼠作为受试动物，随机分为6组，其中4组为TFC等比剂量（6，12，24，48mg/kg）给药组，用灌胃法给药15d后测定其心肌细胞内Ca^2 浓度；另两组分别为阳性对照组和阴性对照组。结果：用药组大鼠心肌细胞内Ca^2 浓度降低，与阴性对照组比较差异显（P＜0．01），且Ca^2 浓度降低的程度与TFC剂量呈正相关。结论：TFC能降低心肌细胞内Ca^2 浓度可能是广枣在临床被用于治疗心脏病症的机理。     

溴化异丙托品和沙丁胺醇舒张气管平滑肌叠加作用的离体研究

目的 :体外比较单用及合用溴化异丙托品和沙丁胺醇对乙酰胆碱、组胺、氯化钾诱导的离体豚鼠气管条收缩作用的影响。方法 :用溴化异丙托品孵育前后组胺、乙酰胆碱、KCl诱发的豚鼠离体气管条的收缩 ;用沙丁胺醇孵育前后组胺、KCl诱发的豚鼠离体气管条的收缩 ;溴化异丙托品和沙丁胺醇合用对组胺、乙酰胆碱和KCl诱导的豚鼠气管条收缩的影响。结果 :乙酰胆碱、组胺诱导离体豚鼠气管条收缩 ,呈典型的剂量反应效应 ,pD2 (达到 5 0 %最大反应的激动剂浓度 )分别为 5 .97± 0 .2 1,6 .4 8± 0 .5 4,用溴化异丙托品孵育后 ,其量效曲线压低 ,pD′2 (拮抗剂效价强度 )分别为 7.99± 0 .34,7.37± 0 .36 ;加用沙丁胺醇后 ,其量效曲线进一步压低。组胺10 -8mol·L-1引起豚鼠气管条收缩 ,10 -4mol·L-1达最大反应 ,pD2 为 6 .6 0± 0 .70 ;用沙丁胺醇孵育后 ,其量效曲线压低 ,pD′2 为 6 .0 6± 0 .2 7。加用溴化异丙托品 6× 10 -8mol·L-1孵育后 ,其量效曲线明显压低 (P <0 .0 1)。氯化钾 6 0mmol·L-1诱导气管条收缩 ,溴化异丙托品和沙丁胺醇抑制其收缩 ,其IC50(抑制 5 0 %最大反应的拮抗剂浓度 )分别为 4 .78×10 -6,3.18× 10 -6mol·L-1。两者合用 ,其抑制作用明显增强 (P <0 .0 1)。结论 :溴化异丙托品和沙丁胺     

DDPH对豚鼠心室乳头状肌细胞电压与频率依赖性的电生理作用

目的　观察１ （２,６ 二甲基苯氧基） ２ （３,４ 二甲氧基苯乙氨基） 丙烷盐酸盐〔１ （２,６ ｄｉｍｅｔｈｙｌｐｈｅｎｏｘｙ） ２ （３ ,４ ｄｉｍｅｔｈｏｘｙｐｈｅｎｙｌｅｔｈｙｌａｍｉｎｏ） ｐｒｏｐａｎｅ ｈｙｄｒｏｃｈｌｏｒｉｄｅ, ＤＤＰＨ〕对豚鼠右心室乳头状肌细胞电压与频率依赖性的电生理作用。方法　采用常规细胞内玻璃微电极技术,分别以０－０２Ｈｚ、２ Ｈｚ 的刺激频率,观察ＤＤＰＨ（１ ～５０ μｍｏｌ·Ｌ－１） 对豚鼠右心室乳头状肌细胞动作电位（ＡＰ） 各参数的影响,并采用０－１ ～３－３ Ｈｚ 的刺激频率和提高Ｋ＋ 浓度（２－７ ～１５ ｍｍｏｌ·Ｌ－ １）将静息膜电位除极化到不同的水平,观察了ＤＤＰＨ（１０μｍｏｌ·Ｌ－１）对豚鼠右心室乳头状肌细胞动作电位零相最大除极化速率（ Ｖｍａｘ）频率与电压依赖性的抑制作用。结果　ＤＤＰＨ以浓度依赖降低豚鼠右心室乳头状肌细胞动作电位振幅（ＡＰＡ） 、缩短动作电位复极５０ ％ 时程（ＡＰＤ５０） 、延长动作电位复极９０％ 时程（ＡＰＤ９０） 并抑制Ｖｍａｘ ,但不明显改变静息膜电位（ＲＰ）,其作用在刺激频率为２ Ｈｚ 时较０－０２ Ｈｚ 时更为明显。对Ｖｍａｘ 呈现出刺激频率     

Hemodynamic and electrophysiological effects of a novel positive inotropic drug, OPC-8212, in normal and "failing" guinea pig heart preparations

OPC-8212, 3,4-dihydro-6-[4-(3,4-dimethoxy-benzoyl)-1-piperazinyl]-2 (1H)-quinolinone, significantly decreased heart rate and increased contractility (+ dP/dt) and coronary flow in isolated, perfused guinea pig Langendorff and work-performing heart preparations. The effect on contractility, but not on coronary flow, was significantly greater when the negative chronotropic effect was prevented by pacing. In guinea pig hearts made incompetent by aortic stenosis, OPC-8212 produced a significant increase in contractility and coronary flow and greater negative chronotropic effects than in control hearts. OPC-8212 improved the work performance of normal and "failing" isolated work-performing guinea pig hearts during pressure load and during volume load. In electrophysiological studies, OPC-8212 enhance Vmax, amplitude, and duration of fast action potentials (APs) in guinea pig papillary muscles. Tetraethylammonium (TEA)-induced slow APs were also potentiated with respect to Vmax, amplitude, and duration. OPC-8212 in the absence of TEA also lowered the voltage threshold for inducing the slow APs. Positive inotropic effects, but not the slow APs, of guinea pig papillary muscles were greatly enhanced by OPC-8212 at higher frequencies of stimulation (2-3 Hz), indicating an important mechanism of action that may be at least in part independent of Isi.     

7-溴化乙氧苯四氢巴马汀的抗心律失常作用

7-溴化乙氧苯四氢巴马汀(EBP)10mg/kg对小鼠乌头碱、豚鼠哇巴因、兔肾上腺素诱发的心律失常有明显对抗作用;2mg/kg对大鼠冠脉结扎和再灌注引起的心律失常有保护作用;EBP能降低离体豚鼠乳头状肌及右房自律性,延长不应期,增加收缩性。EBP明显延长豚鼠乳头状肌APD_(20),APD(90),不影响APA,RP,OS,V_(max)。     

3,6-(二甲氨基)-二苯骈碘杂六环依地酸盐对豚鼠心肌特性的影响

在豚鼠心室肌标本上,利用固定频率起搏技术,研究了3,6-(二甲氨基)-二苯骈碘杂六环依地酸盐(IHC-72)对豚鼠右心室乳头状肌生理特性的影响,IHC-72对豚鼠心室肌呈剂量依赖性负性变力作用,其IC_(50)为0.21±s0.07mmol·L~(-1);延长功能不应期,降低肾上腺素诱发的自律性,对兴奋性则无明显影响,IHC-72对频率依赖性正阶梯现象和静息后增强效应也呈抑制作用,实验结果提示,IHC-72不但抑制心肌细胞钙的跨膜转运,它还影响细胞内储钙的释放。     

国产烟浪丁对豚鼠乳头状肌生理特性的影响

烟浪丁(NICO)对豚鼠乳头状肌的收缩力,有剂量依赖性抑制作用;降低乳头状肌的自律性,对其兴奋性和功能不应期(FRP)无明显影响。普萘洛尔和1.90mmol/L NICO,均使ISO量-效曲线平行右移,且心肌收缩力仍可达到给药前的最高水平,符合竞争性拮抗的特点。维拉帕米使CaCl_2量—效曲线非平行右移,最大收缩幅度明显降低;大剂量(3.80mmol/L)的NICO,亦使最大收缩幅度明显下降。     

Pharmacological studies of celiprolol: I. Beta-blocking effect, intrinsic sympathomimetic activity, vasodilating and hypotensive effects

The beta-blocking effect, intrinsic sympathomimetic activity (ISA), and vasodilating and hypotensive effects of celiprolol were tested. 1. Celiprolol competitively antagonized the isoproterenol-induced positive chronotropic and inotropic effects in guinea pig right atrial and papillary muscles and isoproterenol-induced guinea pig tracheal relaxation with pA2 values of 8.03, 7.98 and 6.43, respectively. 2. In dogs, isoproterenol-induced increases in cardiac contractility and heart rate were markedly inhibited by celiprolol (83.1 and 84.8%, respectively), while isoproterenol-induced hypotension was suppressed only by 16.8%. 3. Celiprolol increased the beating rate of the right atrium and relaxed the trachea isolated from normal and reserpinized guinea pigs. Celiprolol also potentiated the contractility of the left atrium isolated from reserpinized animals. These effects of celiprolol were antagonized by propranolol. 4. Celiprolol concentration-dependently relaxed rat femoral arteries contracted by methoxamine. The concentration-relaxation curve was shifted to the right by pretreatment with propranolol. 5. Orally administered celiprolol produced long lasting hypotension in conscious SHR without any heart rate change. 6. These results indicate that celiprolol is a highly cardioselective beta-blocker with a significant ISA, which contributes to its vasodilatory and hypotensive effects.     

Influence of thyroid hormone on the positive inotropic effects mediated by alpha- and beta-adrenoceptors in isolated guinea pig atria and rabbit papillary muscles.

Effects of thyroxine treatment for 7--11 days on the positive inotropic effects mediated by alpha- and beta-adrenoceptors were studied in isolated guinea pig atria and rabbit papillary muscles. In guinea pig atria, the thyroxine treatment inhibited the positive inotropic effect of lower concentrations of phenylephrine (PHE), and attenuated the inhibitory effect of phentolamine on the PHE response. The effect of isoproterenol (ISO) was potentiated by the thyroxine treatment. In rabbit papillary muscles, the thyroxine treatment shifted the dose--response curve for PHE to the right and attenuated the inhibitory effect of phentolamine on the PHE response. Propranolol, in both guinea pig atria and rabbit papillary muscles, inhibited the PHE response more effectively in preparations from thyroxine-treated animals than in controls. In guinea peg atria, the attenuation of the PHE response mediated by alpha-adrenoceptors was observed after the thyroxine treatment for only 2 days, whereas the potentiation of the ISO response required the thyroxine treatment for a longer period. It was concluded that the thyroxine treatment attenuated the positive inotropic effect mediated by alpha-adrenoceptors and potentiated that mediated by beta-adrenoceptor-mediated positive inotropic effects due to the thyroxine treatment may be independent of each other.     

Influence of thyroid hormone on the positive inotropic effects mediated by α- and β-adrenoceptors in isolated guinea pig atria and rabbit papillary muscles

Effects of thyroxine treatment for 7–11 days on the positive inotropic effects mediated by α- and β-adrenoceptors were studied in isolated guinea pig atria and rabbit papillary muscles. In guinea pig atria, the thyroxine treatment inhibited the positive inotropic effect of lower concentrations of phenylephrine (PHE), and attenuated the inhibitory effect of phentolamine on the PHE response. The effect of isoproterenol (ISO) was potentiated by the thyroxine treatment. In rabbit papillary muscles, the thyroxine treatment shifted the dose—response curve for PHE to the right and attenuated the inhibitory effect of phentolamine on the PHE response. Propranolol, in both guinea pig atria and rabbit papillary muscles, inhibited the PHE response more effectively in preparations from thyroxine-treated animals than in controls. In guinea pig atria, the attenuation of the PHE response mediated by α-adrenoceptors was observed after the thyroxine treatment for only 2 days, whereas the potentiation of the ISO response required the thyroxine treatment for a longer period. It was concluded that the thyroxine treatment attenuated the positive inotropic effect mediated by α-adrenoceptors and potentiated that mediated by β-adrenoceptors in guinea pig atria and rabbit papillary muscles, and that the changes in the α- and β-adrenoceptor-mediated positive inotropic effects due to the thyroxine treatment may be independent of each other.