Effect of C5a on isolated guinea pig atria

Cleavage of the complement protein C5 by activation of the complement system yields a low molecular weight fragment, C5a. Previous reports of other researchers indicate that among the biological activities of C5a is an ability to alter cardiac function. However, these studies have varying results. The goal of the present study was thus to determine both the chronotropic and inotropic effects of guinea pig C5a and the tachyphylaxis to guinea pig C5a in isolated atria of the guinea pig. Isolated right atria respond to guinea pig C5a with a consistent concentration-related positive inotropic and chronotropic response. An inotropic response to guinea pig C5a was seen in both spontaneously beating right atria and paced left atria. The inotropic and chronotropic responses to guinea pig C5a in the right atria were clearly tachyphylactic. Studies using the H2 receptor antagonist metiamide indicate that the positive chronotropic response to guinea pig C5a is at least in part a histamine-mediated response. Further studies are required to determine whether the conflicting results in various studies are due to the use of C5a from various species.     

药根碱对离体豚鼠心房的作用

药根碱使豚鼠左房收缩力和+dF/dt依浓度地增加,-dF/dt/df下降,收缩及舒张时间延长,并提高肾上腺素诱发的左房自律性降低乳头状肌的自律性。延长左房功能性不应期,降低右房自搏频率.药根碱能明显增强心肌的正性阶梯现象,对双脉冲刺激及静息后增强效应无影响。实验表明,药根碱对心肌的作用与小檗碱相似。其正性肌力作用与外Ca~(2+)内流有关,而不涉及细胞内Ca~(2+)的释放。     

乙醇对离体豚鼠心房肌的作用

目的　观察乙醇 (ethanol)对豚鼠离体心房肌生理特性的影响 ,并探讨其作用机制。方法　采用豚鼠左右离体心房测定ethanol对其自动节律、收缩力、功能不应期、静息后增强效应和正阶梯现象的影响。结果　ethanol(12 5 ,2 5 0 ,5 0 0 ,10 0 0 ,2 0 0 0mmol·L-1)明显降低豚鼠离体右心房肌的收缩力 ,同时减慢心率 ;ethanol(12 5 ,2 5 0 ,5 0 0 ,10 0 0 ,2 0 0 0mmol·L-1)抑制豚鼠离体左心房肌的收缩力 ,明显抑制左心房静息后增强效应 ;高浓度ethanol(10 0mmol·L-1、2 0 0mmol·L-1)延长左心房的功能不应期 ,并且抑制左心房正阶梯现象。结论　ethanol具有降低心房自律性、抑制心房肌收缩力、抑制左心房静息后增强效应、延长左心房功能不应期和抑制左心房正阶梯现象的作用 ,其负性变频和负性变力作用可能与抑制心肌细胞内贮钙的释放有关     

蜂毒肽对离体豚鼠心房的双向作用(英文)

目的:研究蜂毒肽(Mel)对离体豚鼠心房的作用。方法:累积浓度法测定Mel给药前后左房收缩幅度及右房频率,观察量效曲线及时效曲线。观察钙离子通道阻滞剂Ver对Mel作用的影响。结果:低浓度Mel(0.1-0.8μmol·L~(-1))对左心房产生正性肌力作用;高浓度Mel(1.6-12.8μmol·L~(-1))产生负性肌力作用。Mel对右心房产生正性频率作用。Mel的双向作用可被Ver 0.3μmol·L~(-1)压低。结论:Mel对离体豚鼠左心房收缩具双向作用,对右心房具正性频率作用。Mel对左心房收缩的双向作用可被Ver压低,提示Mel对心房的作用可能通过电压依赖性钙通道。     

蛇床子素对离体豚鼠心房的作用(英文)

目的:研究蛇床子素对离体豚鼠心房的作用及与Ca~(2 )的关系.方法:钙拮抗剂Ver对照,电刺激左房收缩,累积浓度法测定给Ost前后左房收缩幅度,给药间隔15 min,计算pA_2或pD_2′;观察Ost对左房收缩正阶梯、静息后增强作用。收缩反应由XWT-204台式平衡记录仪描记.结果:Ost、Ver产生浓度依赖性负性肌力作用,抑制高K~ Iso恢复的左房收缩;非竞争性拮抗Iso、CaCl_2正性肌力作用,相应pD_2′值分别为4.41±0.13和6.53±0.22,4.90±0.15和6.91±0.17;抑制正阶梯,大剂量使之翻转,对静息后增强作用弱.结论:Ost对心房抑制作用与Ver相似,但强度较后者弱,可能抑制胞外钙内流.     

Stimulation of guinea pig isolated atria by aflatoxins.

Acute effects of aflatoxins (AF), and in particular cardiac actions, have not been examined as much as chronic toxicity. Thus, in the present study we evaluated the effects of specific AF on isolated guinea pig atria. Isoprenaline (ISO, 4x10(-9)), AFB(1) (3x10(-6) and 6x10(-5) M) and AFG(1) (3x10(-6) and 6x10(-6) M) contracted the isolated guinea pig atria, leaving the preparation hyperresponsive to ISO. These properties of AF are of interest as they could be responsible of certain cardiotoxic effects described in the literature.     

Inotropic and chronotropic activity of berberine on isolated guinea pig atria

The cardiac effects of berberine were studied in isolated right and left atrial preparations from guinea pigs. In spontaneously beating right atria, berberine (1 X 10(-5) -3 X 10(-4) M) caused bradycardia, which was not prevented by atropine (1 X 10(-7) M). Over the same concentration range, berberine increased developed force (dF) in left atria electrically driven at 1.5 Hz. This occurred in both untreated and reserpine-treated tissues as well as in the presence of 5 X 10(-7) M propranolol and 1 X 10(-5) M phentolamine. At a stimulation frequency of 1.5 Hz, left atrial responses to each concentration of berberine reached steady state in approximately 10 min. Concentrations of berberine greater than 3 X 10(-4) M depressed dF and increased resting tone until eventually the left atria failed to contract. Analysis of the effects of berberine on the contractile waveform of left atria showed a concentration-dependent increase in maximal positive dF/dt, maximal negative dF/dt, time to peak tension, and relaxation time. When maximal negative dF/dt was normalized for changes in dF (-dF/dt/dF), berberine showed inhibition of the relaxation process. Berberine had only slight effects on post-rest potentiation and paired pulse stimulation, but enhanced the response of left atria to increases in stimulation frequency. From these results, it appears that berberine has a unique profile of action in isolated guinea pig atrial tissue, showing both positive inotropic and negative chronotropic activity. Berberine produces its positive inotropic effect by enhancing both the force-velocity relationship and the duration of the active state.(ABSTRACT TRUNCATED AT 250 WORDS)     

甲基葡糖苷对豚鼠离体心房的正性肌力作用

目的　观察甲基葡糖苷对豚鼠离体心房的正性肌力作用 ,并探讨其作用机制。方法　采用豚鼠离体左右心房 ,测定药物对心房肌收缩力、右心房心率 ,以及对静息后收缩和正阶梯现象的影响 ,并测定大鼠心肌细胞膜Na+ K+ ATP酶活性。结果　甲基葡糖苷显著增强心房肌收缩力 ,减慢右心房心率 ,且呈剂量依赖性 ;能明显增强左心房静息后收缩和正阶梯现象 ,并能显著抑制大鼠心肌细胞膜Na+ K+ ATP酶活性。结论　甲基葡糖苷具有加强心房肌收缩力 ,降低右心房心率的作用 ,其正性变力作用可能与抑制心肌细胞膜Na+ K+ ATP酶活性 ,促进心肌细胞外钙内流和内钙释放有关     

苄基四氢巴马汀对豚鼠乳头状肌和心房的作用

用离体豚鼠心乳头状肌观察苄基四氢巴马汀(BTHP)对其生理特性及对心肌细胞动作电位的影响。结果表明BTHP 80μM明显延长功能性不应期,抑制肾上腺素诱发的自律性,对兴奋性则影响不大。对动作电位,5-100μM BTHP可延长ERP和APD,这种作用呈浓度和时间依赖性,但对Fc、APA、和Vmax则无明显影响。BTHP 50μM还能显著减慢用利血平处理及未处理的离体豚鼠右房频率,对左房收缩力则稍有增加。结果提示降低心肌自律性、延长ERP和APD与BTHP抗心律失常的机理有关。     

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.     

前胡丙素对豚鼠心房和兔主动脉条的钙拮抗作用

前胡丙素(Pra—C)非竞争性抑制CaCl_2和高钾除极化所致兔主动脉条的收缩,pD’_2值分别为4.9和5.0;抑制5—HT诱导的依外钙性收缩,但不影响依内钙性收缩及NE诱导的收缩;Pra—C5～50μmol/L浓度依赖性地抑制豚鼠左房收缩力和阶梯现象;Pra—C抑制血管与心脏的IC_(50)之比为1:8。结果提示Pra—C对血管和心脏的抑制作用可能与拮抗Ca~(2+)有关,且主要影响经PDCs的外钙内流。     

钩藤碱和异钩藤碱对豚鼠心房的负性变时和变力作用

钩藤碱(Rhy)及异钩藤碱(Isorhy)呈剂量依赖性减慢右心房自发节律,且不被Atr阻断,二药非竞争性地拮抗Iso和组胺正性变时作用,其pD_2值分别为Iso 5.45和5.57,H 5.28和5.48,并能取消CaCl_2的正性变时效应,Rhy和Isorhy还剂量依赖性地抑制心房收缩力,在1μmol·L~(-1)普萘洛尔存在下,二药对苯肾上腺素正性变力作用的量效曲线是非竞争性拮抗,其pD_2值分别为43.6和4.43.Rhy和Isorhy 0、3mmol·L~(-1)能显著抑制左心房静息后增强效应和阶梯现象.结果提示,Rhy和Isorhy的负性变时和变力作用,似与二药抑制心肌细胞膜Ca~(2+)转运有关。     

Effects of human anaphylatoxins on guinea pig atria

Purified human C3a and C5a produce positive inotropic effects on spontaneously contracting atria isolated from guinea pigs. The increased amplitude of contraction induced by C5a has a threshold at 1 X 10(-9)M. This effect is concentration dependent, increasing by 180% at 1.7 X 10(-7)M C5a. The threshold concentration for a C3a-induced effect is four times greater than that for C5a. The C3a-induced effect is also concentration dependent, maximizing at 1 X 10(-7)M. Above that concentration, the increased response to C3a reaches a plateau value at approximately a 70% greater amplitude than that of untreated tissue. Unlike effects induced by anaphylatoxins in other tissues, these positive inotropic responses are not tachyphylactic. The same atrium will respond repeatedly to either C3a or C5a for a period of up to 4 h. Studies with histamine, leukotriene and prostaglandin inhibitors revealed that the anaphylatoxin-induced responses are not solely histamine mediated. Cimetidine partially inhibited the response of isolated guinea pig atria to C5a (e.g. 25%) and failed to affect the response of this tissue preparation induced by C3a. FPL 55712 inhibited the response to both anaphylatoxins by approximately 40%. The atrial response to C3a was inhibited by more than 70% by indomethacin, whereas the response to C5a was unaffected. This is the first report characterizing the specific action of purified C3a and C5a on isolated cardiac tissue. It was concluded that C3a acts primarily via prostaglandins and leukotrienes while C5a affects contractile intensity via vasoamines and leukotrienes.     

四氢异喹啉类衍生物P91024对实验性心律失常和豚鼠离体心房肌的作用

目的:研究四氢异喹啉类衍生物P91024[化学名:1-{1-(6-甲氧基-2-萘基)乙基}-2-对硝基苄基-6,7-二甲氧基-1,2,3,4-四氢异喹啉氢溴酸盐]对实验性心律失常和豚鼠离体心房肌的作用.方法:采用氯化钙、氯化钡、肾上腺素诱导心律失常动物模型,观察灌胃给P91024对实验性心律失常的作用.采用豚鼠离体心房肌实验方法,测定P91024给药前后对心房静息后增强及正性阶梯现象的影响.结果:P91024 30和60 mg·kg-1能降低氯化钙诱发大鼠室颤的发生率(P＜0.01),缩短窦律恢复时间(P＜0.05).P91024 60mg·kg-1可缩短氯化钡诱发大鼠心律失常的持续时间(P＜0.05).并且,P91024 26.1和52.2 mg·kg-1能缩短肾上腺素诱发豚鼠心律失常的持续时间(P＜0.05).P91024 5×10-5mol·L-1能明显翻转豚鼠离体心房肌的正性阶梯作用(P＜0.01)和降低静息后增强作用(P＜0.01).结论:P91024具有明显的抗实验性心律失常作用,抑制豚鼠离体心房肌静息后增强现象及翻转正性阶梯现象.显示本品可能是一种特异性钙拮抗剂.     

Paradoxical effects of calcium-glucagon interaction on cardiac muscle contractility of isolated guinea pig atria.

The interrelationships of calcium and glucagon, and calcium and Isuprel were investigated in spontaneous and paced isolated guinea pig atria. Positive force responses with glucagon were in part both frequency and [Ca+2]o-dependent. Negative inotropic responses were observed with high concentrations of glucagon (5.0 microgram/ml) and calcium (10.0 mM). Persistence of a positive inotropic response of the atria to Isuprel (1.0 microgram/ml) and high [Ca+2]o (10 mM) was seen. Catecholamines stimulate c-AMP production in guinea pig atria while glucagon may not. The negative inotropism produced via calcium-glucagon interaction is consistent with the known inhibitory action of high calcium concentration on adenylyl cyclase and stimulation of phosphodiesterase. It is hypothesized that since glucagon does not activate c-AMP in this tissue then the combined action of high calcium and glucagon leads to degeneration of contractility; with Isuprel and high calcium, atrial contractility is maintained via Isuprel's c-AMP activation.     

Protective action of cardiac DT-diaphorase against menadione toxicity in guinea pig isolated atria

In myocardial preparations isolated from guinea pigs, 2-methyl-1, 4-naphthoquinone (menadione) causes an increase in contractility that is strictly related to the generation of reactive oxygen species (ROS) as a consequence of quinone metabolism. In heart, menadione undergoes one-electron reduction to semiquinone, a reaction mainly catalysed by mitochondrial NADH: ubiquinone oxidoreductase. It is also converted to hydroquinone by the soluble two-electron reductase, DT-diaphorase, and is conjugated with GSH by glutathione S-transferase. In order to assess the role of DT-diaphorase in cardiac responses to menadione, we examined the effects of both a specific inhibitor (dicoumarol) and an inducer (beta-naphthoflavone) of the enzyme on the inotropic action of the quinone. In electrically driven left atria of guinea pig, 4 microM dicoumarol significantly enhanced the positive inotropic effect of menadione, especially at the lower concentrations of the quinone. In myocardial preparations isolated from guinea pigs treated with beta-naphthoflavone (80 mg/kg i.p.for 2 days), DT-diaphorase activity was enhanced (+36% with respect to control animals, P < 0. 01), whereas the activities of the other enzymes involved in menadione metabolism were not modified. In these preparations, menadione caused a significantly lower increase in the force of contraction than in atria from untreated animals; moreover, pretreatment with beta-naphthoflavone caused a significant decrease in the menadione-induced oxidative stress, as evaluated from the GSH redox index. Taken together, these results demonstrate that cardiac DT-diaphorase does not contribute to ROS generation, but represents a detoxification system.