强心扩血管药羟苯氨酮对大鼠,猫和狗心脏血流动力学的影响

为了解强心扩血管新药羟苯氨酮( oxyphenamone,9003 )对在体心血管系统的效应,用多导生理仪与电磁流量计测定大鼠,猫与狗的心脏血流动力学参数。结果表明,静注羟苯氨酮引起血压与血管阻力中度下降,心输出量,心肌收缩力与收缩力变化速度,冠状动脉和股动脉血流量明显增加。羟苯氨酮对心率与左室压的影响呈现种系差别,它增加狗的左室收缩压与压力变化速度,降低左室舒张末期压力,小剂量羟苯氨酮(1或3mg·kg^-1)引起狗的心率轻度降低,剂量增到6mg·kg^-1,心率中度加快。羟苯氨酮不影响猫的心率与左室压。大鼠静注羟苯氨酮后引起心率,左室收缩压与压力变化速度降低,左室舒张末期压力无变化。羟苯氨酮对心脏血流动力学的影响有待用病理模型作进一步观察。     

羟苯氨酮对实验性心肌缺血的治疗作用

目的研究强心扩血管新药羟苯氨酮(oxyphenamone)对心肌缺血的治疗作用。方法用多导生理记录仪和电磁流量计测定心脏血流动力学参数，观察药物对阻断冠脉致急性心肌梗死猫心脏生理功能的影响。形成异丙肾上腺素致大鼠心肌缺血坏死模型，从心肌酶学及病理形态学方面评价药效。结果羟苯氨酮(2-8 mg·kg^-1,iv)可剂量依赖性地降低心梗猫的心率、血压、血管阻力与张力时间指数(TTI)，轻度增加心肌收缩力与心输出量，不影响左室压与心脏作功。羟苯氨酮(4-8 mg·kg^-1,ip)可明显减轻异丙肾上腺素致大鼠心肌肌酸磷酸激酶(CPK)、丙二醛(MDA)与血清谷草转氨酶(GOT)活性变化与病理形态学损伤。结论羟苯氨酮对心肌缺血性损伤有明显治疗作用。     

强心扩血管药羟苯氨酮对离体心肌与血管的作用

为阐明强心扩血管药羟苯氨酮对心肌与血管的直接影响,采用离体心脏,离体心肌与血管制备,以心肌张力、心率、冠脉流量及血管平滑肌张力为观察指标。结果显示:给离体大鼠心脏灌流羟苯氨酮0.1～1μmol·L^-1可使心肌收缩力和冠脉流量明显增加,心率轻度减慢。羟苯氨酮剂量依赖性地增加豚鼠乳头肌和左房肌张力,并减慢右房频率。羟苯氨酮(1～50μmol·L^-1)非竞争性地对抗KCl,5-HT和CaCl₂致狗冠状动脉,基底动脉和肠系膜动脉的收缩,显示它有松弛血管平滑肌的作用。与磷酸二酯酶抑制剂类药物米力农作比较,两者的正性肌力作用与扩血管作用相似。然而,羟苯氨酮减慢心搏频率,米力农则增加心率。提示羟苯氨酮有直接正性肌力、负性频率与扩血管作用。     

羟苯氨酮对麻醉狗心脏血流动力学与心肌氧消耗的影响*

目的:研究强心扩血管新药羟苯氨酮对心肌氧消耗的影响。方法:用多导生理记录仪和电磁流量计测定麻醉开胸狗心脏血流动力学参数,用血气分析仪测定动脉与冠状窦血氧含量,计算心肌氧代谢参数。结果:羟苯氨酮iv 0．5～4mg·kg~(-1)轻度减慢心率,中度降低血压、左室作功、冠脉阻力与总外周血管阻力,短暂增加心输出量与冠脉流量,明显降低心肌氧摄取率与氧消耗量。结论:羟苯氨酮降低心肌氧消耗与心脏负荷,增加心肌供血,有利于对心肌缺血的治疗。     

羟苯氨酮对离体鼠心停灌-复灌损伤的保护作用

目的研究羟苯氨酮对全心停灌-复灌损伤的影响。方法采用离体大鼠心脏停灌40 min-复灌30 min模型，从心脏功能、心肌能量代谢、抗氧化、线粒体钙超载及超微结构等方面观察药物作用。结果停灌前和复灌时给予羟苯氨酮(1~10 μmol·L^-1)明显增加复灌时心肌收缩力与冠脉流量，降低冠脉流出液的肌酸磷酸激酶(CPK)活性，对抗损伤所致的心肌三磷酸腺苷(ATP)与磷酸肌酸(PCr)含量降低，增强心肌抗氧化能力，对抗线粒体钙超载，使线粒体超微结构保持得比较完整。结论羟苯氨酮明显对抗停灌-复灌致心肌损伤，为该药保护再灌注损伤提出有力依据。     

羟苯氨酮保护大鼠心脏对抗心肌缺血-再灌注损伤

目的研究强心扩血管新药羟苯氨酮(oxyphenamone)对心肌缺血-再灌注损伤的保护作用。方法对离体或在体大鼠心脏，阻断冠脉前降支10 min后行再灌注15 min(离体)或30 min(在体)，形成心肌缺血-再灌注损伤模型，从心电图、心肌酶学与心肌超微结构等方面观察药效。结果羟苯氨酮(离体心脏灌流1-10 μmol·L^-1，或静脉注射0.1-1.0 mg·kg^-1)剂量依赖性地明显减少再灌注时的心律失常，对抗损伤所致心肌CPK，LDH与MDA的变化，减轻心肌超微结构损伤。结论羟苯氨酮明显保护离体和在体大鼠心肌对抗冠脉阻断所致缺血-再灌注损伤。     

氨利酮的药理作用与临床应用

氨利酮是最近用于临床并证实有较好效果、副作用小的一种治疗心力衰竭的新药。心力衰竭患者静脉注射或口服该药后,血流动力学明显改善,随着心肌收缩力的增加,心排血量及心脏指数增加,左室充盈压降低,周围血管阻力减小。研究证明本品尚有血管扩张作用。起效快,作用持久而恒定,对心脏无毒性作用。不引起心律失常。     

羟苯氨酮对豚鼠心肌细胞膜Na+和Ca2+ 离子通道的影响羟苯氨酮对豚鼠心肌细胞膜Na+和Ca2+ 离子通道的影响

目的探讨羟苯氨酮(oxyphenamone)的正性肌力作用机制。方法用膜片钳全细胞记录技术测定心肌细胞膜Na⁺ 电流与L型Ca²⁺电流。结果羟苯氨酮剂量依赖性地明显抑制豚鼠心肌细胞膜Na⁺ 电流，促进Na⁺ 通道失活，并延长其恢复时间；它对Ca²⁺电流的影响呈双向性，2～10 μmol·L^-1 使电流增加，促进钙通道的激活过程；20与50 μmol·L^-1时则使Ca²⁺电流明显抑制。结论羟苯氨酮的正性肌力作用不是通过激活钠通道，也不完全依赖于激活L型钙通道，它对钠通道的抑制和在高浓度时对L型钙通道的抑制提示该药可能具有抗心律失常作用。     

左西孟旦的药理、毒理学研究综述

目的:对正性肌力类新药左西孟旦的药理、毒理学研究资料进行整理综述,为临床用药提供参考.方法:查阅了近10年来有关左西孟旦的临床前、临床研究资料并加以分类整理.结果:左西孟旦为钙离子增敏剂类心衰治疗药,为西孟坦的光学异构体,作为正性肌力药物用于短期失代偿性心力衰竭的治疗;左西孟旦与心脏肌钙蛋白C(心脏肌原纤维细丝)的结合可以增强心脏肌钙蛋白C对钙离子的敏感性,增强心肌收缩力,而无需提高细胞内的钙浓度,不影响心率,心肌耗氧量未见明显增加;本品还具有独特的双重作用模式,能增加心脏输出并使静脉、动脉和脑血管扩张,降低前负荷和后负荷,改善冠脉血流;另外,本品在改善心脏泵血功能时不增加心率;急性心肌梗死病人使用本品,其血液动力学和临床症状也可获得改善.结论:左西孟旦具有疗效确切、耐受性好、毒副作用低等优点,可用于急性心力衰竭的治疗.     

心脏组胺能药物——组胺H_2受体激动剂的新进展

在发达国家中,由于人口老化和其他心血管疾病治疗的改进,心力衰竭(HF)发病的增加,已成为人们健康的主要问题。强心甙及拟交感药仍是多年来用于强心疗法的两类药物。但由于强心甙可诱发心律失常及慢性依赖性,拟交感药则不能口服,因而限制了它们的使用。在过去的10年里,为更有效地治疗充血性心力衰竭(CHF),发展了大量新型强心药,包括氨力农、米力农、硫马唑、依诺昔酮、匹罗昔酮、伊马唑坦、Cl-930、indolidan和匹莫苯。所有这些药物均主要是通过选择性地抑制心肌上3′、5′-环磷酸腺苷磷酸二酯酶Ⅲ(cAMP PDE Ⅲ)而发挥作用。但对这些新型的非甙、非儿茶酚胺类强心药的作用众说纷纭。促使心率加快和导致心律失常是这类药物的主要不良反应。尽管这些药物肯定能改善疾病时血流动力学状况和心脏功     

Impact of increased venous pressure on kidney function and mortality in cardiovascular patients with preserved ejection fraction

Abstract

Background: Right but not left ventricular hemodynamic parameters have been found to be independently associated with adverse renal outcomes in patients with acute decompensated heart failure (HF).

Aim: To investigate the hemodynamic profile of patients without acute decompensated heart failure and left ventricular ejection fraction >50% referred for elective left and right heart catheterization and to correlate left and right filling pressures, stroke volume and arterial blood pressure to renal function parameters. Subsequently, we tested the hypothesis that right ventricle and left ventricle hemodynamic parameters can predict all-cause mortality in our non-HF subjects.

Methods: Between October 2009 and November 2010, 151 consecutive patients referred for elective left and right heart catheterization were studied and consequently followed up for a mean period of 8?years in order to identify all-cause mortality. Patient’s initial cohort was subdivided in two groups according to right atrial pressure. The RAPR_LOW group (Right Atrium Pressure ≤ 9?mmHg) and the RAPR_HIGH group (Right Atrium Pressure > 9mmHg)

Results: No correlation between blood pressure, pulmonary capillary wedges pressure, cardiac index, stroke volume and stroke volume index (SVI), and parameters of kidney function was observed. However, a weak, although, significant correlation between right atrial pressure (RAP) and modification of diet in renal disease (MDRD) (r = –0.202; p?=?.014) could be detected. RAPR_LOW patients had a statistically significant lower MDRD value of 16.6?mL/min/1.73 m² than RAPR_HIGH patients. Increased RAP (HR = 2.03; 95% [CI]: 1.05 to 3.9; p?=?.025) and age (HR = 1.08, 95% [CI] 1.04–1.12, p?<?.001) independently predicted all-cause mortality during follow up.

Conclusions: Our study demonstrates that right ventricular preload affects renal function in patients with preserved systolic function and that neither aortic systolic pressure nor left ventricle pressure indices were related to estimated glomerular filtration rate. Furthermore, we demonstrate for the first time that an increased RAP is able to predict a worse prognosis in patients with preserved ejection fraction independently of well-established risk factors, such as blood pressure and SVI.     

重组人脑钠肽对慢性心衰犬血流动力学和肾功能的影响

目的研究国产重组人脑钠肽(rhBNP)对慢性心衰犬血流动力学及肾功能的影响。方法用右心室快速起搏(RVP)或狭窄下腔静脉(TIVCC)形成犬的心衰模型。结果RVP心衰犬iv rhBNP后,平均动脉压(MAP)、左室内压(LVSP)、LVdp/dt、肺动脉压(PAP)、左室舒张末期压(LVEDP)、总外周阻力(TPR)及肾血管阻力(RVR)呈剂量依赖性下降,LVdp/dt/P、左室做功(LVW)、心输出量(CO)和心率(HR)无明显改变;TIVCC心衰犬在iv同剂量rhBNP后,MAP,LVEDP和CO下降,其他心功能指标无明显改变。两种心衰犬给药后尿量和尿钠排出量均增加。结论rhBNP有舒张血管和利尿作用,能明显降低心衰犬的心脏前后负荷,不影响心脏收缩功能。     

NITRIC OXIDE INHIBITION IN AN OVINE MODEL OF HEART FAILURE

1. The role of nitric oxide (NO) in congestive heart failure was investigated by studying the acute haemodynamic, hormonal and renal effects of N^G-monomethyl-l -arginine (l -NMMA), a nitric oxide inhibitor, given as incremental bolus doses in six sheep before (normal) and after induction of heart failure (HF) by rapid left ventricular pacing (LVP). 2. l -NMMA caused significant initial dose-dependent rises in left ventricular systolic pressure, mean arterial pressure (MAP), peripheral resistance (PR) and left atrial pressure and declines in cardiac output in both normal and HF states (maximum response in 2–6 min). These responses were all but abolished when l -arginine was given concurrently with l -NMMA. The dose-response curve for the l -NMMA-induced rise in MAP was shifted to the right following LVP (P<0.05), which is consistent with previous observations of blunted NO synthase activity in HF. A subsequent decline in MAP and PR to below prebolus levels was observed 30–60 min after l -NMMA administration in the paced state. No significant hormonal or renal effects were observed. 3. In conclusion, the present study confirms the important haemodynamic role played by endogenous NO in the normal state and demonstrates a blunted pressor response to NO inhibition in this model of heart failure.     

Influence of intravenous infusion of ethanol on regional blood flow in conscious rats

Abstract— The effects of intravenous infusions of ethanol and saline (0·9% NaCl) on mean arterial pressure (MAP), heart rate (HR), total peripheral resistance (TPR), cardiac contractility (dP/dt_max) and systemic haemodynamics were studied in conscious, unrestrained rats by the radioactive microsphere technique. Saline (0·03 and 0·06 mL min^?1 kg^?1 for 12 min each dose) in the time-control group did not affect MAP, HR, TPR, dP/dt_max or vascular conductances in any organs or beds. While the low dose ethanol (2·4 mg min^?1 kg^?1) did not alter MAP, HR, TPR, systemic haemodynamics or dP/dt_max, the high dose (4·8 mg min^?1 kg^?1) slightly reduced MAP and TPR but did not affect HR, cardiac output or dP/dt_max. Both doses of ethanol vasodilated the intestine and spleen, but vasoconstricted the skin. The high dose caused additional vasodilatation in the heart and testes and the low dose also constricted the skeletal muscle bed. Our results show that ethanol, at non-hypotensive or slightly hypotensive doses, has marked vasodilator effects in the heart, intestine, spleen and testes.     

CPU228, a derivative of dofetilide,relieves cardiac dysfunction by normalizing FKBP12.6, NADPH oxidase and protein kinase C ε in the myocardium

Objectives The aim of this study was to determine if CPU228, a derivative of dofetilide, is more effective than dofetilide in attenuating isoproterenol‐induced heart failure by recovering downregulated FK506 binding protein (FKBP12.6), and suppressing oxidative stress, upregulated NADPH oxidase and protein kinase C ε (PKCε) hyperphosphorylation in the myocardium. Methods Heart failure was induced by isoproterenol (1 mg/kg s.c. for 5 days) in male Sprague‐Dawley rats. Intervention with either CPU228 or dofetilide (2 mg/kg on Days 3–5) was then conducted in vivo and in vitro. Key findings Isoproterenol produced compromised left ventricular systolic pressure, left ventricular pressure rise (dp/dt_max) and fall (dp/dt_min), and left ventricular end‐diastolic pressure, associated with oxidative stress, abnormal FKBP12.6, NADPH oxidase p67phox and PKCε in the myocardium. CPU228 was more effective in attenuating these changes than dofetilide in vivo. Dofetilide produced a prolonged QTc to replace a shortened one. In primary neonatal cardiomyocytes, cultured with isoproterenol and treated with either CPU228 or dofetilide at 10^?8, 10^?7 and 10^?6 mol/l, isoproterenol produced a hyperadrenergic state characterized by downregulated FKBP12.6, upregulated NADPH oxidase p67phox and PKCε in vitro. CPU228 was more effective than dofetilide in recovering these changes in a dose‐dependent manner without a prolonged QTc. Conclusions CPU228 was more effective than dofetilide in attenuating heart failure by normalizing isoproterenol‐induced changes, including downregulation of FKBP12.6, upregulation of NADPH oxidase and PKCε hyperphosphorylation in vivo and in vitro.     

Effect of Piper betle on cardiac function,marker enzymes,and oxidative stress in isoproterenol-induced cardiotoxicity in rats

The present study was designed to investigate the cardioprotective potential of Piper betle (P. betle) against isoproterenol (ISP)-induced myocardial infarction in rats. Rats were randomly divided into eight groups viz. control, ISP, P. betle (75, 150, and 300?mg/kg) and P. betle (75, 150, and 300?mg/kg) + ISP treated group. P. betle leaf extract (75, 150, or 300?mg/kg) or saline was orally administered for 30 days. ISP (85?mg/kg, s.c.) was administered at an interval of 24?h on the 28^th and 29^th day and on day 30 the functional and biochemical parameters were measured. ISP administration showed a significant decrease in systolic, diastolic, mean arterial pressure (SAP, DAP, MAP), heart rate (HR), contractility (+LVdP/dt), and relaxation (?LVdP/dt) and increased left ventricular end-diastolic pressure (LVEDP). ISP also caused significant decrease in myocardial antioxidants; superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH), and myocyte injury marker enzymes; creatine phosphokinase-MB (CK-MB) isoenzyme and lactate dehydrogenase (LDH) along with enhanced lipid peroxidation; thiobarbituric acid reacting species (TBARS) in heart. Pre-treatment with P. betle favorably modulated hemodynamic (SAP, DAP, and MAP) and ventricular function parameters (?LVdP/dt and LVEDP). P. betle pre-treatment also restored SOD, CAT, GSH, and GPx, reduced the leakage of CK-MB isoenzyme and LDH along with decreased lipid peroxidation in the heart. Taken together, the biochemical and functional parameters indicate that P. betle 150 and 300?mg/kg has a significant cardioprotective effect against ISP-induced myocardial infarction. Results of the present study suggest the cardioprotective potential of P. betle.     

卡维地洛对麻醉犬血流动力学的影响

目的　观察国产卡维地洛（ｃａｒｖｅｄｉｌｏｌ,Ｃａｒ）对动物血流动力学的影响,全面了解该药对心血管系统的作用。方法　杂种家犬麻醉下ｉｖ０－１、０－３、１ｍｇ·ｋｇ－１Ｃａｒ,记录心电、血压、左心室内压、心输出量。结果　Ｃａｒｉｖ给药可引起麻醉犬平均动脉压、心率、左心室内压及其最大变化速率、左心室做功及总外周血管阻力明显下降,给药后１ｍｉｎ即开始起效,给药后１～５ｍｉｎ达最大效能,并具有剂量依赖性,１ｍｇ·ｋｇ－１剂量药效可持续至给药后４５ｍｉｎ,Ｃａｒ对心输出量及左室舒张末压无明显影响。结论　Ｃａｒ具有较广泛的心血管效应,除通过扩张外周阻力血管降低血压外,尚具有降低心率、抑制心肌收缩性能的作用;试验结果同时提示国产Ｃａｒ兼具α肾上腺素受体和β肾上腺素受体拮抗作用,支持该药为具有Ｓ（－）和Ｒ（＋）构型的外消旋化合物。