Effects of vagal blockade on neurohumoral systems in conscious dogs with heart failure.

It has been hypothesized that a decreased activity of vagal afferents might contribute to the activation of neurohumoral systems in congestive heart failure. Therefore, we studied the effects of vagal nerve blockade by local anesthesia on neurohormones in six conscious dogs before and after induction of heart failure by rapid right ventricular pacing (250 beats/min, 10 days). In healthy dogs, vagal blockade significantly increased plasma vasopressin levels (from 1.5 +/- .6 to 13.7 +/- 10.5 pg/ml, p less than 0.02), without significantly affecting plasma catecholamines and renin. After 10 days of pacing, mean arterial pressure and cardiac output were decreased, right atrial and pulmonary arterial pressures and plasma levels of norepinephrine, dopamine, and atrial natriuretic peptide were increased. In this state, vagal blockade significantly increased plasma renin activity (from 1.52 +/- .43 to 3.18 +/- .54 ngAI/ml/h, p less than 0.02) and plasma vasopressin (from 4.2 +/- 3.3 to 89.1 +/- 54.9 pg/ml, p less than 0.02), this increase being significantly higher than in healthy dogs. We conclude that in these dogs with low cardiac output state, which resembles early heart failure, vagal afferent activity is increased and effectively suppresses renin and vasopressin. This does not exclude the possibility that in later stages of heart failure vagal afferent dysfunction may develop, resulting in neurohumoral disinhibition.     

Cardiovascular effects of AR-L115 BS in conscious dogs with and without chronic congestive heart failure

AR-L115 BS is a phenyl-imidazo-pyridine derivative that combines positive inotropic and vasodilator properties. To analyze the mechanisms of action of AR-L115 in the presence or absence of heart failure, we administered it intravenously to conscious dogs (seven normals and eight with a volume-overload heart failure). In normals, at a plasma level around 1,000 ng/ml, AR-L115 BS increased left ventricular (LV) peak (+) dP/dt (+48%; p less than 0.02) and heart rate (+29 beats/min; p less than 0.05) without altering significantly cardiac filling pressures or cardiac output. The mean aortic pressure and the systemic vascular resistances (-20%; p less than 0.02) were reduced, but plasma renin activity (PRA) was unchanged. In heart failure, the same plasma level increased peak (+) dP/dt by 36% (p less than 0.01), but heart rate stayed unchanged. Mean aortic pressure, systemic vascular resistances (-20%; p less than 0.01), and LV end-diastolic pressure (-9.1 mm Hg; p less than 0.01) all dropped significantly, while cardiac output increased slightly; PRA did not rise significantly. After beta-blockade, the increases in peak (+) dP/dt and the changes in systemic vascular resistances were markedly reduced. In conclusion, AR-L115 BS has strong positive inotropic and vasodilator effects, both of which are partially dependent on the level of the sympathetic tone in the intact animal. These combined properties improve hemodynamics in heart failure; this improvement is already significant at relatively low plasma levels, at which deleterious changes in heart rate or PRA are absent.     

辛伐他汀对慢性心力衰竭患者血清肌钙蛋白I及心功能的影响

目的：探讨辛伐他汀对慢性心力衰竭（CHF）患者血清心肌钙蛋白I（cTnI）和心功能的影响。方法：入选失代偿性CHF患者102例,将其随机分为辛伐他汀组（n=59）和对照组（n=43）,两组均给予常规抗心力衰竭治疗,辛伐他汀组在常规治疗基础上加用辛伐他汀10mg,每晚1次,疗程12周。对比两组治疗前后左心室舒张末期内径（LVEDD）、左心室射血分数（LVED及血清cTnI浓度的变化。结果：治疗12周后,辛伐他汀组LVEDD、cTnI明显下降（64．5±4．3SV46．7±3．2）mm,P〈0．01、（2．13±0．92vs1．09±0．35）μg/L,P〈0．01,LVEF升高（320±4．1VS43．2±3．9％,P〈0．01）,并与对照组比较差异有统计学意义。结论：对于CHF患者辛伐他汀10mg,每晚1次,可以保护心脏功能,提高射血分数,降低cTnI。     

Effects of converting-enzyme inhibition on cardiorenal hemodynamics in patients with chronic congestive heart failure

The role of the renin-angiotensin system in cardiorenal function in patients with severe chronic congestive heart failure was investigated. A single oral dose of captopril in 16 patients significantly increased cardiac index and reduced arterial blood pressure and total systemic vascular resistance. These changes were significantly greater in subjects with higher baseline plasma renin activity (PRA). During 7-day captopril therapy, renal plasma flow distinctly increased in 10 patients in whom renal function was followed. The increase found in renal plasma flow was greater in subjects with higher PRA. Yet, the reduction in renal vascular resistance was much greater than that of total systemic vascular resistance, even in patients with lower PRA. Simultaneous infusion of aprotinin in eight of these subjects did not affect the captopril-induced increase in renal plasma flow, despite the suppression of plasma bradykinin levels; these responses were the same in both PRA subgroups. The results suggest that captopril reduces total systemic vascular resistance in patients with chronic congestive heart failure through inhibition of the renin-angiotensin system and that the preferential renal vasodilator effect of captopril might be the sole result of this inhibition, with the kallikrein-kinin system or kinin-mediated prostaglandins not playing a major role.     

番茄红素对慢性心力衰竭大鼠的保护作用及机制研究

目的探讨番茄红素对慢性心力衰竭大鼠心功能的影响及可能机制。方法结扎大鼠左冠状动脉前降支制备慢性心力衰竭大鼠模型,21只Wistar大鼠分为假手术组、心力衰竭对照组及心力衰竭番茄红素处理组。采用超声心动图检测各组大鼠心功能,酶联免疫吸附法(ELISA)检测大鼠血浆氧化应激即丙二醛(MDA)和超氧化物歧化酶(SOD)水平。采用实时定量反转录聚合酶链反应(RT-PCR)及蛋白印迹法分别检测各组大鼠心脏肌浆网钙调控蛋白(SERCA2a)的表达。结果与假手术组相比,心力衰竭对照组左心室射血分数显著降低,而左心室舒张末内径(LVEDD),左心室收缩末内径(LVESD)显著升高(P<0.05)。同时心力衰竭对照组血浆氧化应激水平显著升高,而心脏SERCA2amRNA及蛋白的表达水平显著下调(P<0.05)。给予番茄红素处理4周后,可明显改善心力衰竭大鼠上述指标的异常(P<0.05)。结论番茄红素能改善慢性心力衰竭大鼠心功能,其机制可能与降低心力衰竭大鼠氧化应激水平,从而上调慢性心力衰竭大鼠心肌SERCA2a蛋白表达有关。     

超声心动图对心脏再同步化治疗心力衰竭患者疗效的评价

目的应用超声心动图来评价心脏再同步化治疗(CRT)心力衰竭患者的疗效。方法 16例慢性心力衰竭患者行CRT植入,于术后1周、3个月、6个月对AV和VV间期进行优化,观察术前及术后1周、3个月、6个月左心室舒张末、收缩末的直径(LVDD、LVDS)及左室舒张、收缩末期容积(LVEDV、LVESV)和左室射血分数(LVEF),及心脏同步化指标的变化。结果与术前比较,术后3个月、6个月心功能均得到改善,6 min步行距离增加,LVEF增加,LVDD、LVDS、LVEDV和LVESV缩小,心脏同步化指标得到改善。结论在超声指导下对AV、VV间期进行优化后心脏再同步化治疗可改善双心室的同步性和心脏功能。     

螺内酯对慢性心力衰竭患者心脏自主神经功能的影响

目的：观察螺内酯对慢性心力衰竭（CHF）患者心脏自主神经功能的影响。方法：回顾性收集某院2012年12月-2014年12月收治的CHF患者52例,按照给药方案的不同分为观察组和对照组。对照组26例采取基础抗心衰方案治疗;观察组26例在基础抗心衰治疗上加用螺内酯（20 mg·d^-1）,治疗前1天及治疗后16周行动态超声心动图检查,通过系统分析得出心率变异性（HRV）的时域及频域分析指标。结果：与对照组比较,螺内酯治疗16周后HRV明显改善（t=13.406,P<0.05）;时域指标：全部窦性R-R间期的标准差（SDNN）、全部窦性R-R间期差值的均方根（rMSSD）、每5分钟窦性R-R平均值的标准差（SDANN）、SDNN的均值（SDNNI）均明显升高（t=5.829,10.256,6.005,7.128,P<0.05）;频域指标：低频（LF）、高频（HF）也明显提高（t=9.231,7.441,P<0.05）。结论：螺内酯可明显改善CHF患者的HRV,改善心脏自主神经功能。     

达格列净对非糖尿病慢性心力衰竭兔的心功能及心肌重构影响

目的　探讨达格列净对非糖尿病慢性心力衰竭兔的心功能和心肌重构的影响。方法　将18只健康雄性新西兰大白兔随机分为假手术组、心力衰竭组和达格列净组,每组6只。假手术组只开胸不手术,心力衰竭组和达格列净组开胸后采用主动脉缩窄法经12周建立非糖尿病慢性心力衰竭模型,观察各组一般情况。术后13周达格列净组经强饲法给予达格列净1 mg/（kg·d）,假手术组和心力衰竭组给予等量生理盐水,共干预10周。各组于术前、术后12周、药物干预10周后行超声心动图检查;药物干预10周后检测体质量及白细胞计数、血红蛋白、总蛋白、白蛋白、钾、钠、随机血糖、渗透压和N端前脑钠素（NT-proBNP）;处死动物后,测量全心和左心室质量,并行HE、Masson及免疫组化染色观察心肌细胞形态、纤维化程度,计算胶原组织分数和胶原（Collagen）Ⅰ或CollagenⅢ阳性面积百分比。结果　达格列净可改善心力衰竭兔的食欲减退、精神萎靡、活动减少和呼吸急促等症状。药物干预10周,达格列净组左心室射血分数较心力衰竭组明显升高,且较术后12周明显升高（P＜0.05）。3组间白细胞计数、总蛋白、白蛋白、血清钾、钠、随机血糖、血浆渗透压差异均无统计学意义,达格列净组和心力衰竭组血红蛋白水平低于假手术组,而达格列净与心力衰竭组差异无统计学意义。达格列净组心脏外形较心力衰竭组减小,且全心质量、左心室质量以及左心室/体质量均低于心力衰竭组（P＜0.05）。HE染色显示达格列净可明显改善心肌细胞的形态学变化。Masson染色显示达格列净组胶原组织分数较心力衰竭组明显降低（P＜0.05）,免疫组化染色提示达格列净组心肌组织CollagenⅠ、CollagenⅢ阳性面积百分比较心力衰竭组降低（P＜0.05）。结论　达格列净可抑制心力衰竭后心肌重构,其机制可能与抑制心肌组织中CollagenⅠ和CollagenⅢ的表达和心肌纤维化有关。     

Effects of ACE inhibition and angiotensin II type 1 receptor blockade on cardiac function and G proteins in rats with chronic heart failure

1. Inhibition of the renin-angiotensin system (RAS) improves symptoms and prognosis in heart failure. The experimental basis for these benefits remains unclear. We examined the effects of inhibition of ACE or blockade of angiotensin II type 1 (AT1) receptor on the haemodynamics, cardiac G-proteins, and collagen synthesis of rats with coronary artery ligation (CAL), a model in which chronic heart failure (CHF) is induced. 2. Rats were orally treated with the ACE inhibitor trandolapril (3 mg kg(-1) day(-1)) or the AT1 receptor blocker L-158809 (1 mg kg(-1) day(-1)) from the 2nd to 8th week after CAL. CAL resulted in decreases in the left ventricular systolic pressure and its positive and negative dP/dt, an increase in the left ventricular end-diastolic pressure, and the rightward shift of the left ventricular pressure-volume curve. Long-term treatment with either drug improved these signs of CHF to a similar degree. 3. Cardiac Gsalpha and Gqalpha protein levels decreased, whereas the level of Gialpha protein increased in the animals with CHF. Long-term treatment with trandolapril or L-158809 attenuated the increase in the level of cardiac Gialpha protein of the animals with CHF without affecting Gsalpha and Gqalpha protein levels. Cardiac collagen content of the failing heart increased, whose increase was blocked by treatment with either drug. 4. Exogenous angiotensin I stimulated collagen synthesis in cultured cardiac fibroblasts, whose stimulation was attenuated by either drug. 5. These results suggest that blockade of the RAS, at either the receptor level or the synthetic enzyme level, may attenuate the cardiac fibrosis that occurs after CAL and thus affect the remodelling of the failing heart.     

慢性心力衰竭患者采用稳心颗粒与美托洛尔联合治疗的效果及对心功能血管内皮功能的影响

目的探讨慢性心力衰竭患者采用稳心颗粒与美托洛尔联合治疗的效果及对心功能、血管内皮功能的影响。方法选取2016年1月至2017年2月在本院住院治疗的慢性心力衰竭患者286例,分为观察组和对照组各143例,观察组给予稳心颗粒与美托洛尔联合治疗,对照组给予美托洛尔治疗,比较2组治疗的效果及对心功能[左室舒张末期内径(LVEDD)、左室射血分数(LVEF)]、血管内皮功能[内皮细胞微粒(EMPs)含量、加压前后肱动脉管径变化的百分比(FMD)]的影响。结果观察组总有效率为95.11%,明显高于对照组的总有效率(76.72%)且差异具有统计学意义(P<0.05)。2组治疗后LVEDD、EMPs均较治疗前降低且差异具有统计学意义(P<0.05),观察组治疗后LVEDD、EMPs低于对照组且差异具有统计学意义(P<0.05);2组治疗后LVEF、FMD均较治疗前升高且差异具有统计学意义(P<0.05),观察组治疗后LVEF、FMD高于对照组且差异具有统计学意义(P<0.05)。结论稳心颗粒与美托洛尔联合治疗能够显著提高慢性心力衰竭患者的治疗效果,并显著改善患者心功能及血管内皮功能。     

胺碘铜对快速右心室起搏致心力衰竭犬心室电生理特性的影响

AIM: To study the effects of amiodarone (Ami) on cardiac electrophysiologic properties and ventricular fibrillation threshold (VFT) in right ventricular rapid pacing-induced congestive heart failure (CHF) dogs. METHODS: Dogs (n = 25) were randomly allocated into 3 groups: A) control group; B) CHF group induced by right ventricular rapid pacing (4 pulses.s-1) for 4-5 wk; C) CHF models p Ami 300 mg.d-1 for 4-5 wk. The electrophysiologic parameters and VFT were evaluated by electric stimulation and monophasic action potential (MAP) recording. RESULTS: In CHF models, ventricular MAP duration (MAPD90), ventricular late repolarization duration (VLRD), and intra-ventricular conduction time (IVCT) were prolonged by 43%, 318%, and 19%, respectively; the ratio of ventricular effective refractory period (VERP) to MAPD90 (VERP/ MAPD90) and VFT were decreased by 13% and 48% respectively; the dispersion of ventricular recovery time (RT-D) was increased by 185%. In CHF models, Ami had no effects on ventricular MAPD90, but increased VERP/ MAPD90, IVCT, and VFT by 15%, 10%, and 67%, respectively, shortened VLRD by 87%; and decreased RT-D by 87%. Ami had no significant influences on the hemodynamic parameters of the CHF dogs. CONCLUSION: Ami normalizes the cardiac electrophysiologic properties in CHF dogs.     

Effects of amiodarone on cardiac electrophysiology in right ventricular rapid pacing-induced heart failure dogs

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血脂康胶囊对慢性心力衰竭患者心功能及C反应蛋白的影响

目的探讨血脂康胶囊对慢性心力衰竭患者的心功能及C反应蛋白（CRP）的影响。方法48例冠心病慢性心力衰竭患者按就诊顺序随机分为2组,对照组（22例）应用血管紧张素转换酶抑制剂,β-受体阻滞剂、利尿剂和洋地黄制剂治疗,血脂康组（26例）在对照组基础上加用血脂康0．6g,治疗半年,治疗前后采用超声心动图测定心功能,酶联免疫分析法测定CRP水平。结果血脂康组总有效率88．5％,优于对照组68．2％（P〈0．05）。血脂康组CRP在治疗后为（2．87±1．34）mg／L,较治疗前[（4．34±1．13）mg／L]显著降低（P〈0．05）,且显著低于对照组（P〈0．05）。治疗后2组心脏功能均得到明显改善,且血脂康组改善较对照组明显。结论血脂康在改善心功能的同时能降低血清CRP水平。     

血脂康胶囊对慢性心力衰竭患者心功能及C反应蛋白的影响

Objective To investigate the effect of Xuezhikang capsule on chronic heart failure (CHF) and C-reactive protein (CRP). Methods Forty-eight patients were randomly divided into two groups. Control group (22 cases) had angiotensin-converting enzyme inhibitor β-blockers, diuretics and digitalis preparations treatment. Based on the same treatment of the control group, patients in Xuezhikang group (26 cases) were given extra Xuezhi-kang capsule 0.6g, twice a day. Echocardiography was taken to the two groups, and CRP level was tested by en-zyme-linked immunoabserbent assay. Results After treatment, the total effective rate of Xuezhikang group (88. 5%) was higher than that of control group (68.2%). CRP in Xuezhikang group(2.87±1.34) mg/L was decreased after treatment (P < 0.05). After treatment, the heart function of both group were significantly improved, especially in Xuezhikang group. Conclusion Xuezhikang capsule improves the heart function and reduces serum CRP level in chronic heart failure patients.     

Acute hemodynamic effects of nisoldipine and pimobendan in conscious pigs with chronic heart failure

The acute systemic hemodynamic effects of the calcium antagonist nisoldipine and the pyridazinone-derivative pimobendan, a phosphodiesterase inhibitor with vasodilating as well as positive inotropic properties, were studied in conscious pigs with chronic heart failure. Left ventricular (LV) dysfunction, manifested by a 25% decrease in cardiac output (CO), a 35% increase in systemic vascular resistance (SVR), and a doubling of the left ventricular filling pressure, was induced by a proximal ligation of the left circumflex coronary artery. Two to three weeks after myocardial infarction, cumulative 10-min infusions of either nisoldipine (0.05, 0.1, 0.25, and 0.5 micrograms/kg/min), pimobendan (2.5, 5, 12.5, and 25 micrograms/kg/min) or the solvents were administered. Infusion of the solvents did not affect any of the hemodynamic variables. Both nisoldipine and pimobendan normalized CO and exhibited a similar cardiac profile [systemic vasodilatation, reduction in left ventricular filling pressure, and an increase in heart rate (HR)] except for the significantly (p less than 0.05) larger increase in LVdP/dtmax with pimobendan (85%) than with nisoldipine (45%). In animals with heart failure, lower doses of both nisoldipine (twice) and pimobendan (four times) were needed to elicit a 30% reduction in SVR than in animals with normal pump function. For both drugs, the slope of the line describing the vasodilatory and positive inotropic properties shifted more in favor of the vasodilatory actions during heart failure (p less than 0.05). We conclude that in swine with chronic LV dysfunction nisoldipine, despite its lack of inotropic properties, appeared to improve ventricular function to the same extent as the primary positive inotropic agent pimobendan.     

卡维地洛治疗慢性心力衰竭的疗效观察

目的：观察卡维地洛治疗慢性心力衰竭的疗效。方法：64例慢性心力衰竭患者随机分为2组，常规治疗组予以利尿剂、血管紧张素转换酶抑制剂和洋地黄等治疗，卡维地洛组在此基础上加用卡维地洛，治疗6个月后对比观察2组临床症状、心率、血压、心功能级别和左室射血分数变化情况。结果：卡维地洛组各项指标均明显改善，患者生活质量明显提高。结论：卡维地洛可作为治疗慢性心力衰竭的有效药物应用于临床。     

辛伐他汀抑制心肌细胞Rho A、Rho GTPase表达对心室肥厚的影响

目的 探讨辛伐他汀对心力衰竭模型兔抑制心肌肥厚、改善心功能的影响及机制.方法 24只新西兰白兔,均分四组.除假手术组外,通过破坏主动脉瓣和缩窄腹主动脉,增加左心室前、后负荷,建立慢性心力衰竭模型;术后(除心衰对照组)早干预组(即起,连续8周)和晚干预组(第5周起,连续4周)予辛伐他汀每天5 mg/kg灌胃,实验结束取心肌细胞,Westem-blot检测细胞膜Rho A蛋白表达,[γ~-~(32)P]电泳分析Rho GTPase活性;实验前、结束时均行超声心动图检查.结果 心衰对照组室间隔厚度(LVSd)、左心室舒张期内径(LVIDd)、左心室后壁厚度(LVPwd)、左心室收缩期内径(LVIDs)、心脏重量(Hw)、左心室重量(LVW)、心脏/体重(HW/BW radio)、左心室/体重(LVW/BW radio)明显高于假手术和早、晚干预组(P<0.05,P<0.01);左室射血分数(EF)、左室长轴缩短率(FS)明显低于假手术组和早、晚干预组(P<0.05,P<0.01);心肌细胞膜Rho A蛋白表达、Rho GTPase活性明显高于假手术组和早、晚干预组(P<0.01).结论 辛伐他汀可抑制细胞膜RhoA蛋白表达、Rho GTPase活性,从而抑制心肌肥厚、改善心功能.     

卡维地洛对慢性心衰合并肾功能不全患者肾功能的影响

目的:评价卡维地洛对慢性心衰(CHF)合并慢性肾功能不全(CRF)患者肾功能的影响。方法:入选27例CHF合并CRF患者,在充分抗心力衰竭治疗的基础上,加用卡维地洛,观察不同阶段左室射血分数(LVEF)和肾功能的变化。结果:卡维地洛治疗后,LVEF在治疗3个月后开始升高,12个月后显著高于基线水平(p<0.01)。治疗后1个月,血肌酐(Scr)升高(p<0.05),3个月时回落到基线水平以下(p<0.05),12个月时仍低于基线水平(p<0.05);治疗后1个月,内生肌酐清除率(Ccr)先轻度下降(p<0.05),3个月时回升高于基线水平(p<0.01),12个月时仍显著高于基线水平(p<0.01)。卡维地洛对尿微量白蛋白和24h尿蛋白定量影响不大(p>0.05)。结论:第三代β-受体阻滞剂卡维地洛,可改善慢性心衰合并慢性肾功能不全患者的心功能,早期引起肾功能的轻度降低,随后肾功能显著改善。     

瑞舒伐他汀对慢性心力衰竭患者的疗效观察

目的观察瑞舒伐他汀对慢性心力衰竭患者(CHF)的临床疗效。方法 82例冠心病并CHF患者随机分为治疗组46例和对照组36例,对照组患者给予抗心力衰竭的常规治疗;治疗组在对照组基础上加用瑞舒伐他汀治疗,每晚餐时服用20mg,1次/d。两组均治疗6个月。两组分别于治疗前及治疗6个月后测定左室心功能指标及血浆BNP水平。结果治疗6个月后治疗组总有效率显著高于对照组(P<0.05);治疗组的心功能指标及血浆BNP水平的改善均优于对照组(P<0.05或P<0.01)。结论 CHF患者在常规治疗同时加用瑞舒伐他汀治疗,可以显著降低血浆BNP水平,改善心功能。