细辛对狗左室功能的作用及其与去甲乌药硷、异丙肾上腺素的比较

实验表明细辛可使狗左室泵功能和心肌收缩性能明显改善。在心肺制备狗,主要表现为LVSP↑,LVEDP↓,MAP↑,CO↑,HR↑,SV↓,dp/dt_max↑,-dp/dt_max↑,t—dp/dt_max↓,V_px↑,V_ce-cpip↑,V_max↑;在麻醉开胸狗,除MAP降低和SV增加外,对其它指标的作用方向与心肺制备实验结果基本一致;两个实验中测取的Lissajous图形的正向前降支均向右上方移位。从而排除了前、后负荷的影响,说明泵功能的改善似由于细辛增强心肌收缩性能所致。通过细辛与去甲乌药硷、异丙肾上腺素的比较研究,提示三者的作用基本相似,唯SV显示不同的结果。细辛使SV增加,去甲乌药硷、异丙肾上腺素却使SV减少,这可能与细辛增加HR的比率较二者为低密切相关。肾上腺素能β受体阻滞后,细辛增加CO的作用仍然存在,值得进一步研究。     

Effect of vasoactive intestinal peptide on myocardial contractility and coronary blood flow in the dog: comparison with isoproterenol and forskolin

The effects of intracoronary injections of vasoactive intestinal peptide (VIP) on left ventricular (LV) dp/dt, coronary blood flow (CBF), and myocardial oxygen consumption (MVO2) were compared with isoproterenol (ISO) and forskolin in 18 dogs using a preparation in which cardiac output, mean systemic arterial pressure, and heart rate were fixed. In eight dogs in which the effects of VIP and ISO were compared using doses ranging from 2 x 10(-12) to 2 x 10(-8) mol, both agents significantly increased LV dp/dt at doses greater than or equal to 6.6 x 10(-10) mol. At maximal doses (2 x 10(-9) to 2 x 10(-8) mol) the effect of ISO was significantly greater than VIP. Both VIP and ISO significantly increased CBF at all doses, but at maximal doses the effect of VIP on CBF was significantly greater than ISO. The increase in CBF relative to the increase in MVO2, an index of direct coronary vasodilation, was significantly greater for VIP compared with ISO. In 10 additional dogs the effects of VIP and ISO were compared with forskolin given in doses ranging from 2 x 10(-9) to 2 x 10(-7) mol. At maximal doses (2 x 10(-7) mol) the increase in LV dp/dt was similar to VIP but significantly less than ISO, whereas the increase in CBF was similar to ISO but significantly less than VIP. The increase in CBF relative to the increase in MVO2 was significantly greater for forskolin compared with ISO, indicating a direct vasodilator effect.(ABSTRACT TRUNCATED AT 250 WORDS)     

Enhancement of coronary conductance by alpha-human atrial natriuretic polypeptide without effects on myocardial contractility

The effect of synthetic human atrial 28-amino acid peptide (alpha-human atrial natriuretic polypeptide, alpha-hANP) on coronary circulation and cardiac functions was examined in open-chest dogs. Intravenous injection of alpha-hANP increased coronary and systemic conductance, and coronary and aortic blood flow with a significant fall in blood pressure. Continuous infusion of alpha-hANP into the left anterior descending coronary artery (LAD) increased LAD blood flow in a dose-dependent manner. The linear regression analysis revealed the relationship of logit (changes in mean coronary conductance (delta MCC] = 1.45 x log (coronary plasma concentration of alpha-hANP) + 7.51 (r = 0.87, n = 29). REC50 of alpha-hANP was 5.1 microM, where REC50 was the concentration to increase MCC to a half maximum MCC during reactive hyperemia after a 30-s coronary occlusion. alpha-hANP increased coronary conductance with no changes of myocardial oxygen consumption (MVO2) when blood pressure remained constant. Indices of myocardial contractility measured with a strain gauge arch, myocardial force (F), max dF/dt and LV max dp/dt, were not altered by either bolus intravenous injection or continuous intracoronary infusion of alpha-hANP. These results indicated a direct increase by alpha-hANP of coronary and systemic vascular conductance.     

人参茎叶黄酮对狗心脏血流动力学的影响

人参茎叶黄酮20mg/kg(iv)能明显降低麻醉狗的 LVP、(dp/dt)max、TPVR、BP和耗氧量。对心脏泵功能指标 CI、SI 和心肌收缩性指标 dp/dt/CPIP 无显著影响。对反映心肌收缩敏捷度的 t-(dp/dt)max 明显延长(1～40min)。对 CO、PF 无明显影响。     

苦碟子注射液对犬心脏功能和血流动力学的影响

目的考察苦碟子注射液对麻醉开胸犬心脏功能和血流动力学的影响。方法采用麻醉开胸犬模型,测量其心率、心输出量、冠脉流量、心肌耗氧量以及血流动力学各参数。结果苦碟子注射液以2.0、4.0 g.kg-1静脉注射给药可显著增加戊巴比妥钠麻醉犬的心输出量和冠脉流量,降低平均动脉压、左心室内压和左心室舒张末期压力,减少左室内压力变化速度和心肌耗氧量(P<0.05,P<0.01)。结论苦碟子注射液能显著改善麻醉开胸犬血流动力学。     

Coronary vasodilatation following diazepam (Valium)

1. The effects of diazepam (Valium) on coronary and systemic vascular resistance were studied in anaesthetized dogs on cardiopulmonary bypass under conditions of constant heart rate and aortic pressure.2. Pharmacological doses of diazepam uniformly produced coronary vasodilation lasting 30 min; systemic vascular resistance also decreased, but to lesser degree.3. When coronary blood flow was maintained constant at physiological levels, diazepam produced no changes in left ventricular contractility, as assessed by peak LV isovolumetric pressure, dp/dt max, force-velocity, and length-tension relations, whereas previous experiments had demonstrated a positive inotropic effect in a similar preparation in which coronary blood flow was responsive to alterations in coronary vascular resistance.4. In five dogs, complete separation of the coronary and systemic circulations was accomplished by a double pump-oxygenator system; direct intracoronary administration of diazepam produced coronary vasodilatation, but coronary pressure and flow were not altered by administration of diazepam to the systemic circulation.5. It is concluded that diazepam augments myocardial contractility by increasing coronary blood flow. This relationship is independent of extracardiac humoral mechanisms, and appears to require the delivery of diazepam to the coronary circulation.     

人参茎叶皂甙对狗心脏血流动力学的影响

实验表明人参茎叶皂甙(GSL)50mg/kg i.v.可使狗左室泵功能和心肌收缩性发生程度不同的改变,可使 LVP,CO,CI,TPVR,BP,HR,耗氧量,(dp/dt)max,(dp/dt)/CPIP等下降,PF,SI,t-(dp/dt)max 等上升。这些结果与目前掌握的人参根总皂甙对狗血流动力学的影响基本一致。     

Myocardial and haemodynamic effects of phentolamine

1. In cats anaesthetized with pentobarbitone, intravenous infusions of phentolamine ((10-50 mug/kg)/min for 5 min) increased heart rate, left ventricular dp/dt max (without increasing end-diastolic pressure), aortic dp/dt, cardiac output, myocardial blood flow and metabolic heat production.2. Phentolamine-induced increases in myocardial contractility occurred irrespective of the direction or magnitude of the blood pressure change and were maintained well beyond the actual infusion period.3. In cats treated with alprenolol, bretylium or reserpine there was no evidence of increased cardiac contractility following phentolamine administration.4. It is concluded that phentolamine, in doses less than those required to produce significant alpha-adrenoceptor blockade, increased myocardial contractility through an effect on the sympathetic nervous system.     

The effect of heart rate on indices of myocardial contractility in the dog

1. Changes in heart rate were evoked by atrial pacing in anaesthetized dogs with no pretreatment and in dogs given reserpine or guanethidine for 72 h. The effect of alterations in heart rate were related to two indices of myocardial contractility: the maximal rate of change of left ventricular pressure (dp/dt), and an index which was independent of initial fibre length (dp/dt)/IIT, where IIT is integrated isometric tension. 2. An increase in heart rate in control dogs was accompanied by a rise in both dp/dt and (dp/dt)/IIT confirming that the Bowditch staircase does exist in the intact ventricle. The regression line relating heart rate to (dp/dt)/IIT was significantly steeper than that relating heart rate to dp/dt because the reduction in left ventricular preload at high heart rate tends to attenuate the rise in dp/dt. 3. Reserpine, but not guanethidine pretreatment was accompanied by either a slight decrease or no change in (dp/dt)/IIT during pacing. 4. Acute elevation of (dp/dt)/IIT by either calcium or isoprenaline infusion in reserpine pretreated dogs did not restore the Bowditch effect. 5. Acute depression of (dp/dt)/IIT by propranolol and pentobarbitone was accompanied by a greater rise in (dp/dt)/IIT with pacing in control dogs and a rise rather than a fall in reserpine-pretreated dogs.     

灯盏细辛与丹参配伍治疗实验犬冠心病

目的观察灯盏细辛提取物与丹参提取物配伍使用治疗犬冠心病的作用特点。方法设计犬冠状动脉结扎法所致犬心肌缺血模型试验,以确证灯盏细辛和丹参配伍使用后的确切疗效。结果灯盏细辛与丹参配伍能明显降低模型犬血清LDH和CK的含量和活力,减小心肌梗死范围,降低心率、ST段抬高、LVEDP和MVO2,增加CO,升高模型犬LV dp/dt、LV-dp/dt和LVSP,且合用组在作用强度和作用时间上均优于单用两组。结论灯盏细辛与丹参配伍使用在左冠状动脉前降支(LAD)结扎所致犬冠心病模型试验中,在改善模型动物酶学、形态学和心脏血流动力学各指标上作用确切,且配伍使用效果更佳。     

A novel orally active dopamine prodrug TA-870. III. Positive inotropic effect and cardiorenal selectivity in anesthetized dogs.

The effect of TA-870, a novel dopamine prodrug, on the cardiovascular system was studied in anesthetized open- and closed-chest dogs. Intraduodenal administration of less than or equal to 12 mg/kg TA-870 to anesthetized dogs increased left ventricular (LV) dP/dtmax and dP/dt/Pmax. Furthermore, at a lower dose of TA-870 (2 mg/kg), renal vascular resistance (RVR) decreased and renal blood flow (RBF) increased. Similarly, total peripheral resistance (TPR) decreased and cardiac output (CO) increased at less than 4 mg/kg. In an intravenous cumulative dose-response study of TA-870, the plasma-free-dopamine concentration was elevated depending on the dose of TA-870. Renal vasodilation occurred at a low plasma-free-dopamine concentration, whereas a positive inotropic action required higher plasma-free-dopamine. However, the dose-response curve for LVdP/dt/Pmax was steeper than that for RBF or CO. Heart rate was less affected than LVdP/dt/Pmax in open-chest dogs and decreased in closed-chest dogs. Propranolol strongly inhibited the effect of TA-870 on LVdP/dt/Pmax. It also inhibited the effects of TA-870 on TPR and CO to a lesser extent, and the remaining effects were almost completely inhibited by an additional treatment with the dopamine blocker, RS-sulpiride. In conclusion, TA-870 increased myocardial contractility and output by the enteral route, and the latter effect was produced at lower doses with the help of peripheral vasodilation due to the activation of dopamine receptors.     

心喘灵(XC-1)及其衍生物XC-2对麻醉犬血流动力学的作用

本工作比较研究了心喘灵(XC-1)及其衍生物XC-2(8204) 对麻醉开胸犬心脏血流动力学的作用。用递加剂量法静注心喘灵0.5,1.0,2.0和4.0 mg/kg,每二个剂量之间的间隔为5 min,给药后MAP和LVP下降,HR减慢,CI和SI增加,TPR降低,冠状、颈内和股动脉血流增加,血管阻力下降,±LVdp/dt max增加,而LV dp/dt/p改变不明显,LVW,CVP和MVO₂无明显变化。用同法静注同样剂量XC-2的作用和心喘灵相似,但较弱;一次静注5 mg/kg也出现柑似但较弱的作用。它们的作用是通过阻断α和β受体及直接扩张血管所引起。     

巴曲酶对急性心肌缺血犬冠脉节段阻力和流量的影响

犬冠状动脉定量狭窄造成急性心肌缺血,观察巴曲酶(batroxobin)对冠脉循环及血流动力学的影响。结果显示,batroxobin可剂量依赖性地增加缺血心脏冠脉血流量,2BU·kg^-1(0.1BU·kg^-1·min^-1)iv后40min,缺血犬冠脉流量比盐水对照组增加12%,此时小冠脉阻力由4.1±0.5降至3.2±0.5mmHg·min·ml^-1,而大冠脉阻力无明显变化;给药后120min,上述作用仍然持续,且冠脉总阻力降低13%,左室压上升及下降最大速率与盐水对照组相比分别增大14%和16%。结果表明,batroXobin在冠脉低灌流状态下仍可降低小冠脉阻力,增加冠脉流量,这可能是其改善缺血犬冠状循环及心脏功能的机理之一。     

Pharmacology of LY195115, a potent, orally active cardiotonic with a long duration of action

Compound LY195115 is a novel cardiotonic with both inotropic and vasodilator activities. In cat papillary muscles, LY195115 increased contractility in a concentration-dependent manner; its actions were not blocked by either prazosin or propranolol. An intravenous dose of 7.0 micrograms/kg LY195115 resulted in a 50% increase in contractility in anesthetized dogs; comparable inotropic responses were observed in anesthetized cats receiving 10 micrograms/kg i.v. These doses of LY195115 increased heart rates of both dogs and cats by less than 10%. Oral administration of 25 micrograms/kg to conscious dogs was associated with a selective inotropic response that was maximal at 3 h and maintained in excess of 23 h. This effect was not accompanied by gross behavioral changes or emesis. The hemodynamic profile of LY195115 was evaluated in anesthetized beagle dogs. A 60-min infusion of 1.0 microgram/kg/min LY195115 followed by a 5-min infusion of 10 micrograms/kg/min resulted in dose-dependent increases in contractility (LV dP/dt60) and heart rate; doses that increased LV dP/dt60 by 50% increased heart rate by less than 10%. Doses of greater than 5.0 micrograms/kg decreased left ventricular end-diastolic pressure and systemic vascular resistance; mean arterial blood pressure and cardiac output were unchanged. Estimated myocardial oxygen consumption (heart rate times either systolic or mean arterial blood pressure) was not altered by doses as high as 110 micrograms/kg. This balance of inotropic/vasodilator activities may provide a means of improving cardiac function while maintaining myocardial oxygen supply/demand.     

Effects of intracoronary administration of endothelin in anesthetized dogs: comparison with Bay k 8644 and U 46619.

The effects of synthetic endothelin on the coronary circulation were studied in pentobarbital-anesthetized dogs and compared with those of Bay k 8644, a dihydropyridine calcium channel agonist, and U 46619, a thromboxane analogue. Intracoronary bolus administration of endothelin reduced coronary blood flow and increased coronary arterial resistance. Similarly, intracoronary bolus administration of equipotent doses of Bay k 8644 or U 46619 significantly reduced coronary blood flow and increased coronary arterial resistance. The coronary vasoconstrictor effects of endothelin were long-lasting as compared with the transient actions of Bay k 8644 and U 46619. Intracoronary bolus injection of endothelin also reduced left ventricular (LV) dP/dt arterial pressure (MAP), and cardiac output (CO). In contrast, Bay k 8644 increased LVdP/dt but did not alter CO or MAP. Intracoronary bolus injection of U 46619 did not affect MAP, CO, or LVdP/dt. In a separate group of animals, intracoronary infusion of nitrendipine significantly increased coronary blood flow and reduced coronary arterial resistance. Other cardiovascular parameters measured were not significantly altered. In the presence of nitrendipine, the effects of intracoronary administration of endothelin and U 46619 on coronary blood flow, coronary arterial resistance, and LVdP/dt were only partially antagonized. On the other hand, the effects of Bay k 8644 were completely prevented in the presence of nitrendipine. These studies show that at doses which reduce coronary blood flow to the same extent, only endothelin produces myocardial depression in anesthetized dogs. The cardiovascular actions of endothelin were only partially antagonized by nitrendipine, suggesting that mechanisms other than calcium influx through voltage-operated channels are involved.     

Myocardial and circulatory effects of E. coli endotoxin; modification of responses to catecholamines

1. The predominant acute effect of E. coli endotoxin in anaesthetized, ventilated cats was pulmonary hypertension resulting from a 8-12 fold increase in pulmonary vascular resistance. This was followed by decreases in left ventricular (LV) and systemic arterial pressures and in LV dP/dt max. Recovery occurred within 2-4 min and was dependent upon increased sympathetic drive; recovery did not occur in cats treated with the beta-adrenoceptor blocking drug alprenolol.2. The pulmonary vasoconstriction was reduced in cats given compound 48/80 and evidence is presented that it results primarily from histamine release.3. Over the 2-3 h period following endotoxin injection, systemic arterial pressure tended to decrease and heart rate and myocardial metabolic heat production to increase. Myocardial blood flow and LV dP/dt remained fairly stable until the terminal stages of shock.4. The predominant delayed effect of E. coli endotoxin in cats were a markedly reduced stroke volume, an increase in peripheral vascular resistance and a severe metabolic acidosis (arterial base excess-20 mEq/litre). Arterial pO(2) and pCO(2) were not significantly affected. It is concluded that myocardial contractility is maintained at this time through the release of catecholamines and that endotoxin itself depresses contractility.5. The effects of adrenaline and noradrenaline infusions on systolic and diastolic blood pressures, heart rate, cardiac output, myocardial blood flow and LV dP/dt max were markedly reduced in the period 2-3 h after endotoxin. In a few animals some recovery of the response to noradrenaline occurred and was associated with a general circulatory improvement and a reduced metabolic acidosis.     

Prolonged cardiac dysfunction after withdrawal of chronic cocaine exposure in rats

Cocaine abuse causes myocardial dysfunction and induces oxidative stress. However, the reversibility of these effects is unknown. We evaluated myocardial function and oxidative stress after cocaine withdrawal, in a rat model of chronic cocaine exposure. Standard echocardiography and Doppler tissue imaging were performed after 4 weeks (W4) of cocaine administration (2 x 7.5 mg/kg/d, i.p.) and 4 weeks after interruption (W8). At these time points, redox state (reduced glutathione GSH, oxidized glutathione GSH, and GSH/GSSG) as well as activities of GSH peroxidase (GPX), superoxide dismutase (SOD), and catalase were determined in the left ventricle (LV). At W4, LV fractional shortening, posterior wall thickening, systolic myocardial ventricular gradient (SMVG), dP/dt(max), and dp/dt(min) were decreased, compared with control values while LV myocardial thickness was increased. At W8, even though dP/dtmax and dp/dt(min) were restored, myocardial function was still impaired as demonstrated by the decrease in posterior wall thickening, and systolic myocardial velocity gradient. At W4, CAT and GPX activities as well as GSH/GSSG ratio were reduced while SOD activity was increased. Antioxidant markers and redox ratio remained altered 4 weeks after the last injection. Thus, these data demonstrate the persistence of LV dysfunction after cocaine withdrawal, which occurs in a context of a deficit in antioxidant defenses.     

东亚钳蝎毒及其成分抗癫痫肽对心脏和血管的作用

本文报告河北产东亚钳蝎(Buthus martensii Karsch)毒及用柱层析法从粗毒中纯化的抗癫痫肽对心脏、血管的作用。实验结果证明蝎毒能使麻醉免LVP、左室dp/dt升高、心率稍减慢;心得安能对抗蝎毒升高LVP和dp/dt的作用。抗癲痫肽对LVP、dp/dt、心率的影响都不明显。蝎毒使离体豚鼠心脏收缩张力增强,心率减慢,并呈现频繁的心律不齐。心得安能对抗蝎毒增强心脏收缩张力的作用,但不能消除心律不齐。抗癫痫肽使心肌收缩张力下降,心率加快,同时也引起心律不齐。蝎毒能引起兔主动脉条明显收缩,作用强度约为NE的1/5,在蝎毒作用的基础上,妥拉苏林使收缩曲线升高,心得安使曲线降低。抗癲痫肽使兔主动脉条轻微松弛。用光电容积搏动法实验,蝎毒和抗癲痫肽都能使小鼠末稍血管收缩。     

The effect on myocardial contractility of a new beta-adrenergic receptor blocking drug, penbutolol.

1 The inotropic effect of penbutolol, a new beta-adrenergic receptor blocking drug, has been compared with that of propranolol in two similar groups of six subjects each. 2 Inotropic changes were assessed from changes in myocardial contractility index [LV dp-dt/11 T] as well as the slope of the regression line relating LV dp/dt to LVED during incremental pacing. 3 Penbutolol was found to have a significant negative inotropic effect of an order similar to that of propranolol in the respective doses studied.     

重组人脑钠肽及米力农对麻醉犬血流动力学及肾功能的影响

目的观察重组人脑钠肽(rhBNP)对麻醉犬血流动力学和肾功能的作用。方法给麻醉开胸犬恒速输注rhBNP(采用累积给药方式),或iv米力农后,进行血流动力学测定,并测定尿量、尿钠和血钠含量。结果rhBNP可使MAP,LVSP,LVdP/d_t,PAP,LVEDP,TPR及RVR呈剂量依赖性下降,CO有增加趋势,尿量和尿钠排出量呈剂量依赖性增加。米力农则明显降低MAP,PAP,LVEDP,TPR,RBF及RVR,升高LVSP,LVdP/d_t和CO,加快心率,对尿量、尿钠排出量和血钠无明显影响。结论rhBNP能明显降低心脏前后负荷,改善心脏功能;可舒张肾动脉,有扩张血管和利尿排钠作用。米力农则有正性肌力和频率作用,无利尿利钠作用。