重组人脑钠肽对急性心衰犬血管紧张素Ⅱ和内皮素-1的影响

目的研究重组人脑钠肽(rhBNP)对普萘洛尔诱导比格犬急性心力衰竭后血浆血管紧张素Ⅱ(AngⅡ)、内皮素-1(ET-1)、尿量、尿钠、尿钾及血钠、血钾含量的影响。方法静脉推注普萘洛尔诱导急性心力衰竭,静脉滴注普萘洛尔维持心衰,股动脉插管监测血流动力学指标变化,电磁流量计测量心输出量,输尿管插管测量尿量,模块式全自动生化仪测定尿钠、尿钾、血钠和血钾含量,放免法测定血浆AngⅡ和ET-1的含量。结果心衰犬静脉滴注重组人脑钠肽后,AngⅡ和ET-1的含量较基础值降低(P<0.05~0.01),尿量、尿钠明显增加(P<0.05),尿钾含量减少(P<0.05~0.01)。结论rhBNP降低普萘洛尔所致比格犬急性心力衰竭血浆AngⅡ和ET-1的浓度,并具有明显的利钠利尿的作用,对急性心衰产生保护作用。     

卡维地洛对阿霉素诱导的CHF大鼠血流动力学的影响

目的:探讨阿霉素诱导大鼠发生充血性心力衰竭后血流动力学的变化,并观察卡维地洛对相关指标的影响。方法:SD大鼠雌雄不拘,阿霉素腹腔注射累计15mg/kg,分6次给药,1周1次。心衰模型复制成功后,将存活的大鼠分为对照组,阿霉素心衰模型组以及卡维地洛组,检测其血流动力学。结果:与正常对照组相比,心衰模型组的左室内压峰值(LVSP),左室等容收缩期压力最大上升速率( dP/dtmax),左室舒张期压力下降速率(-dP/dtmax)和收缩压均明显降低(均P<0.01),而左室舒张末压(LVEDP)明显升高(P<0.01)。而与模型组相比,卡维地洛组LVSP, dP/dtmax,-dP/dtmax和收缩压均明显均升高(均P<0.01),LVEDP则降低(P<0.01)。结论:卡维地洛可明显改善阿霉素诱导慢性心力衰竭(CHF)大鼠的血流动力学,从而对阿霉素的心肌毒性有潜在的保护作用。     

大鼠舒张性心力衰竭动物模型的建立

目的:建立Wistar大鼠舒张性心力衰竭(DHF)模型.方法:采用腹主动脉缩窄法建立压力负荷型舒张性心衰模型,并通过十六导生理记录仪测定心肌收缩功能指标[左室内压最大上升速率(+ dp/dtmax)、左心室收缩压(LVSP)]和心肌舒张功能指标[左心室舒张末期内压(LVEDP)、左室内压最大下降速率(- dp/dtma...     

氯沙坦对心力衰竭大鼠心肌细胞缝隙连接的作用机制研究

目的观察氯沙坦对心力衰竭(心衰)大鼠心功能的影响并探讨其对心肌细胞缝隙连接的作用机制。方法 SD大鼠60只随机分为假手术组、模型组、氯沙坦高、中、低剂量组,灌胃给药7 d后,采用冠脉结扎复制大鼠心衰模型。测定心功能:左心室压峰值(LVP)、左心室舒张末期压(LVEDP)、左心室内压最大上升速率(+LVdp/dtmax)、左心室内压最大下降速率(-LVdp/dtmax)。采用Western Blot方法测定心肌缝隙连接蛋白43(Cx43)和Cx45的表达。结果氯沙坦能显著改善心衰大鼠心功能,与模型组比较,氯沙坦低、中剂组LVP明显上升(P<0.01),LVEDP明显下降(P<0.05或<0.01),高剂组LVP、+LVdp/dtmax明显上升,LVEDP明显下降(P<0.01);显著提高Cx43表达,降低Cx45表达(P<0.05或<0.01)。结论氯沙坦对心室的间隙连接通道有保护作用,可以提高心室传导速度,从而降低心律失常的发生。     

Liguzinediol对普萘洛尔诱导的急性心衰豚鼠心功能的影响

目的研究Liguzinediol对普萘洛尔所致豚鼠急性心衰模型的治疗作用并评价其效能、效价和治疗指数。方法静脉注射普萘洛尔建立豚鼠急性心力衰竭(AHF)模型后,分组静脉恒速注射给予Liguzinediol(2.85、5.70、11.40、22.80、45.60、91.20 mg·kg-1)及阳性药盐酸肾上腺素(0.31 mg·kg-1),用RM6240多道生理信号采集处理系统记录给药0、5、10、20、40、60、90和120 min时左心室内压最大上升/下降速率(±dp/dtmax)、左心室内压(LVSP)、动脉收缩压(MSP)、动脉舒张压(MDP)和心率(HR)的变化;计算该药的效能、效价和治疗指数。结果 Liguzinediol(11.40、22.80和45.60 mg·kg-1)能有效升高模型豚鼠+dp/dtmax、LVSP、MSP、MDP和HR,降低-dp/dtmax,Liguzinediol(2.85、5.70mg·kg-1)作用较弱,ED50约为12.93 mg·kg-1,治疗指数(LD50/ED50)为131,45.60 mg·kg-1已达最大效能,再加大剂量至91.20 mg·kg-1其效应并不能相应增强。结论 Liguzinediol对急性心衰豚鼠的血流动力学指标有明显的改善作用,其安全性比同类药物高。     

黄芪注射液对慢性心力衰竭大鼠心肌保护作用的研究

目的探讨黄芪对慢性心力衰竭大鼠心功能的保护作用和血清IL-6与TNF-α含量的变化。方法通过腹腔注射阿霉素来建立大鼠的慢性心衰模型,实验分为正常对照组、模型组和黄芪组。黄芪组灌胃给予药物4ml/kg,治疗4周后,对相关指标进行检测。结果与模型组比较,黄芪组有效的降低了左心室质量指数、升高左室收缩压、左室内压最大上升速率和左室内压最大下降速率,降低左室舒张末压,同时降低血清IL-6与TNF-α含量。结论黄芪能够明显的改善阿霉素建立的慢性心衰大鼠的心功能,降低了血清中IL-6与TNF-α含量,推测黄芪改善心功能的作用可能与抑制炎症和心室重塑相关。     

ErbB信号与蛋白激酶B在快速起搏所致猴心衰心肌细胞损伤中的作用

为了研究ErbB受体与蛋白激酶B在心力衰竭发生机制中的作用，建立快速起搏诱导恒河猴心力衰竭模型。采用颈总动脉插管技术，测定左心室最大压力上升速度(LVdp/dt_max)、左心室舒张末期压(LVEDP)、左心室收缩末期压(LVSP)等血流动力学指标；采用电化学发光免疫测定法观察脑钠肽(BNP)含量；采用RT-PCR方法测定ErbB₂、蛋白激酶B(PKB)、Bcl-xl mRNA表达水平；采用Western blotting检测蛋白激酶B活性(phospho-PKB，即磷酸化蛋白激酶B蛋白水平)及凋亡相关基因Bcl-xl的蛋白水平。快速起搏诱导心力衰竭模型恒河猴心肌收缩能力显著下降，心衰标志物脑钠肽水平明显上升(P<0.05)。与对照组比较ErbB₂，PKB及Bcl-xl mRNA表达水平明显下降(P<0.05)，同时心肌组织蛋白激酶B活性显著下降，Bcl-xl蛋白水平也明显下降(P<0.05)。快速起搏所致猴心衰心肌细胞损伤的机制可能与ErbB₂、下游蛋白激酶B、凋亡抑制基因Bcl-xl表达水平下降及蛋白激酶B活性下降有关。     

血管紧张素-(1～7)对慢性心力衰竭大鼠的疗效观察

目的探讨血管紧张素-(1～7)对慢性心力衰竭大鼠的治疗作用及其不同剂量所产生的影响。方法建立大鼠慢性心力衰竭模型,观察不同剂量血管紧张素-(1～7)对心力衰竭大鼠冠状动脉流量、心率及左室收缩压、左心室内压最大上升速率、左心室内压最大下降速率、及心肌梗死范围的影响。结果与未用药组对比,使用不同剂量血管紧张素-(1～7)预处理组冠状动脉流量、左室收缩压,左心室内压最大上升速率及最大下降速率均有明显的提高(P<0.01),梗死区范围均有明显的缩小(P<0.01),但心率各组间无明显差异(P>0.05)。结论血管紧张素-(1～7)促进心力衰竭大鼠的冠状动脉流量和收缩功能恢复,减少心肌梗死范围。     

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。     

线粒体融合素2在糖尿病大鼠心肌损伤中的变化

目的:探讨线粒体融合素2(mitofusin 2,Mfn2)在糖尿病大鼠心肌损伤中的变化。方法:腹腔注射55mg/kg链脲佐菌素复制糖尿病大鼠模型,分为正常组、糖尿病4周组和糖尿病8周组。测定血流动力学指标、大鼠心系数;自动生化分析仪测定血浆肌酸激酶同工酶(creatine kinaseisozyme,CK-MB)水平。RT-PCR检测左室心尖部组织Mfn2的表达。结果:与正常大鼠相比,糖尿病4周、8周大鼠左室发展压、左室最大上升和下降速率、心率、左室做功均明显下降(P<0.05,P<0.01),心室舒张末压上升(P<0.01),心系数(HW/BW)明显增加(P<0.01),血浆CK-MB水平升高(P<0.05,P<0.01),Mfn2mRNA的表达降低(P<0.01);与糖尿病4周相比,糖尿病8周大鼠左室发展压、左室最大上升速率和下降速率、心率及左室做功进一步下降(P<0.05,P<0.01),心室舒张末压升高(P<0.01),HW/BW、CK-MB水平持续性升高(P<0.01),Mfn2mRNA的表达进一步降低(P<0.01)。结论:随着糖尿病病程的延长,糖尿病大鼠心室功能进一步下降,其机制可能与Mfn2的表达降低有关。     

Effect of autonomic blockade on the hemodynamic responses of normal human subjects to acute intravenous milrinone

We studied the hemodynamic effects of four doses of milrinone, administered by intravenous (i.v.) infusion alone and after autonomic blockade with prazosin, propranolol, atropine, and clonidine. Plasma concentrations of milrinone (50-600 ng/ml) were similar to those used for the treatment of cardiac failure and were unaltered by autonomic blockade. When given alone, milrinone induced dose-dependent increases in heart rate (maximum increase 21 +/- 4, SEM, beats/min) and cardiac output (CO) (maximum 44 +/- 9%) and reduced systemic vascular resistance (SVR) by a maximum of 32 +/- 5%. After autonomic blockade, milrinone caused a similar fall in SVR and a smaller but significant (7 +/- 2 beats/min) rise in heart rate, but no change in CO. The increase in CO produced in normal humans by acute i.v. infusions of milrinone depends on intact cardiovascular reflexes.     

汉防已甲素对扩张型心肌病心力衰竭患者血流动力学影响的研究

目的观察静脉注射汉防已甲素(90~120mg)对扩张型心肌病心力衰竭患者血流动力学影响,评价其临床疗效。方法采用Swan-Ganz导管的实验方法,测定用药前及用药后30、60、90、120s血流动力学参数的变化。结果扩张型心肌病心力衰竭患者静注汉防已甲素后5min,SAP(收缩压)、DAP(舒张压)、MAP、RAP(右房压)、TSR、TPVR、PVR开始降低,30~60min时,TSR显著降低(P<0.01),SAP、DAP、MAP显著降低(P<0.05),90min后作用开始减弱,作用持续120min恢复到用药前水平。30~60min,MPAP(平均肺动脉压)降低非常显著(P<0.01),PCWP(肺小动脉楔压)降低显著(P<0.05)。以上参数降低的同时,CO、CI、SVI、SWI升高,用药后30~60minCO、CI较用药前显著升高。结论汉防已甲素降低扩张型心肌病心力衰竭患者的RAP、SAP、DAP、MAP、PCWP、MPAP、TSR、TPVR、PVR及SAP×HR,提高CO、CI、SVI、SWI,降低心脏前后负荷及心肌耗氧量,使心功能改善,对充血性心力衰竭患者有良好的血流动力学作用。     

血液动力学监测系统在急性心力衰竭中的应用

目的　评价无创血液动力学监测系统(Bioz com)对急性心力衰竭(AHF)患者进行实时连续性血液动力学参数监测并指导AHF治疗的可行性。方法　对35 例AHF患者(治疗组)采用自身前后对照方法,在使用速尿或硝酸甘油前后采用Bioz com系统实时连续监测心衰患者的心率(HR)、平均动脉压(MAP)、心排血量(CO)、加速度指数(ACI)、胸腔体液指数(TFC)、左室做功指数(LCWI)、外周血管阻力(SVR)的变化并对参数的变化进行比较;同时与健康体检人员(健康组)进行比较;并与使用Bioz com系统进行监测前的AHF患者(对照组)4周死亡率进行比较。结果　35 例AHF患者,注入速尿或硝酸甘油后能快速增加CO、ACI、LCWI(P<0 01),明显降低TFC、SVR(P<0 01)。与健康组各血液动力学参数进行比较,HR、MAP、CO、ACI、LCWI、TFC、SVR 均有统计学差异(P< 0.05 ~ 0.01)。4 周死亡率治疗组与对照组分别为9/35(25.7%)、13/36(36.1%)(P<0.01)。结论　Bioz com系统在AHF患者中通过监测相关参数变化,为临床治疗和改善预后提供准确可靠依据,值得推广。     

阻断内皮素受体和抑制血管紧张素转化酶在慢性心衰大鼠中的相加作用

目的:评价一种新的内皮素受体拮抗剂tezosentan对慢性心衰大鼠血流动力学的急性作用,并进一步研究该药与血管紧张素转化酶(ACE)抑制剂依那普利合用是否有相加作用。方法:在结扎左侧冠状动脉所致的慢性心衰大鼠中测量血流动力学的指标。结果:心肌梗死3-5周后,大鼠产生慢性心衰,与假手术大鼠相比,慢性心衰大鼠左心室舒张末期压(LVEDP)显著升高,其均值为23-26mmHg,心肌收缩力(左心室dp/dt_(max))降低30％-40％,平均动脉压(MAP)降低大于10％。在慢性心衰大鼠中,静脉注射tezosentan(10mg·kg~(-1))或依那普利(1mg·kg~(-1))显著降低其MAP和LVEDP,并对其心率或dp/dt_(max)无影响。与tezosentan或依那普利单用组相 比,两者合用对慢性心衰大鼠的MAP和LVEDP具有相加作用,对其心率或dp/dt_(max)无显著性作用。结论:急性静脉注射tezosentan改善慢性心衰大鼠心脏血流动力学,降低其LVEDP和后负荷(MAP),其心率和心肌收缩性(dp/dt_(max))并不受影响。Tezosentan的这些有利作用与依那普利相似。而且在抑制ACE作用的基础上,Tezosentan的这些有益作用也是很明显的。因此,tezosentan有望成为急性治疗心衰的有效新药。     

Effects of intravenous infusion of isosorbide dinitrate (ISDN) on acute experimental congestive heart failure

Experiments were undertaken to examine whether and how intravenous infusion of ISDN ameliorated hemodynamics of anesthetized dogs with congestive heart failure. A model of acute congestive heart failure with markedly high left ventricular end-diastolic pressure (LVEDP) and low cardiac index (CI) was induced by occlusion of the left anterior descending coronary artery (LAD) following 30-min infusion of dextran solution containing propranolol in halothane anesthetized open-chest dogs. Five minutes after occlusion of LAD, intravenous infusion of ISDN (100 and 500 micrograms/kg/min for 5 min) decreased the elevated LVEDP, aortic pressure and systemic vascular resistance, and enhanced the reduced CI. These changes produced by ISDN were significant (P less than 0.05 or P less than 0.01) as compared with values just before infusion of ISDN. ISDN at the same doses slightly reduced LVEDP, but did not increase CI in normal dogs which were not subjected to the coronary occlusion and dextran infusion. These results indicate that intravenous infusion of ISDN reduces both pre- and after-load and increases CI in dogs with heart failure, demonstrating that ISDN is useful for the vasodilator therapy of heart failure.     

Combined atorvastatin and coenzyme Q10 improve the left ventricular function in isoproterenol-induced heart failure in rat

The effect of atorvastatin on cardiac remodeling, function, and homodynamic parameters in isoproterenol-induced heart failure was evaluated in the present study. A subcutaneous injection of isoproterenol (5mg/kg/day) for 10 days was used for the induction of heart failure. Isoproterenol administration produced intensive myocardial necrosis and fibrosis with a significant decrease in the arterial pressure indices, heart rate, contractility (LVdP/dt(max)) and relaxation (LVdP/dt(min)), but an increase in the left ventricular end-diastolic pressure. Rats were randomly assigned to control, treatment with only atorvastatin, and treatment with atorvastatin plus coenzyme Q10. Histopathological analysis showed a marked attenuation of myocyte necrosis and interstitial fibrosis in all atorvastatin treated groups (P<0.001). A low dose of atorvastatin (5mg/kg/day) significantly improved the left ventricular systolic pressure, contractility and relaxation (P<0.01). On the contrary, a high dose of atorvastatin (20mg/kg/day) worsened the isoproterenol-induced left ventricular dysfunction by a further reduction of LVdP/dt(max) from +2780 ± 94 to +1588 ± 248 (mmHg/s; P<0.01) and LVdP/dt(min) from -2007 ± 190 to -2939 ± 291 (mmHg/s; P<0.05). Co-administration of coenzyme Q10 with atorvastatin reversed the hemodynamic depression and the left ventricular dysfunction to a high level (P<0.001). There was a lower level of LVEDPs in the atorvastatin+coenzyme Q10 treated groups (3 ± 1 and 4 ± 1.4 versus 8 ± 3.5 and 14 ± 3.6 mmHg, respectively), thereby suggesting improvement in the myocardial stiffness by the combined coenzyme Q10 and atorvastatin treatment. The atorvastatin therapy attenuated myocardial necrosis and fibrosis in isoproterenol-induced heart failure. However, a high dose of the drug considerably worsened the left ventricular dysfunction and hemodynamic depression, which was reversed by coenzyme Q10 co-administration.     

COMPARATIVE HAEMODYNAMIC EFFECTS OF VERAPAMIL, FLECAINIDE, AMIODARONE AND SOTALOL IN THE CONSCIOUS RABBIT

1. The effect of intravenous boluses of verapamil (0.15 mg/kg), flecainide (2 mg/kg), amiodarone (5 mg/kg), and sotalol (l.5 mg/kg) on mean arterial pressure, heart rate (HR), cardiac output (CO), total peripheral resistance (TPR), and peak rate of change of left ventricular pressure (LV dP/dt) were assessed in the conscious rabbit. 2. All four drugs had negative inotropic effects: verapamil reduced peak LV dP/dt by 19±4% (mean±s.e.m.; P<0.01), flecainide by 27 ± 9% (P<0.001), amiodarone by 11 ± 2% (P<0.01) and sotalol by 13 ± 3% (P<0.01). 3. The drugs had different effects on CO as a result of differences in their actions on peripheral blood vessels: verapamil and amiodarone produced, respectively, a 12 ± 4% (P<0.03) and 16 ± 6% (P<0.01) increase in CO associated with a substantial vasodilatory effect (TPR reduced 15 ± 7%[P<0.05] and 20 ± 5% [P<0.01], respectively). Flecainide caused only a small (6 ± 1%; P<0.01) increase in CO and sotalol had no effect on either CO or TPR. 4. Bolus intravenous injections of verapamil, flecainide and amiodarone produced an increase in HR, while sotalol reduced HR by 10 ± 2% (P<0.01). The increase in HR and cardiac output seen with verapamil, flecainide and amiodarone was in part secondary to reflex increase in sympathetic tone and these changes were abolished after total cardiac autonomic blockade. 5. The modest reduction in cardiac performance associated with sotalol was abolished by cardiac autonomic blockade, suggesting that the predominant effect of sotalol on contractility was mediated through its β-adrenoceptor blocking effect.     

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.     

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。