决明子蒽醌苷对两肾一夹高血压大鼠左室心肌肥厚及舒张功能的影响

目的观察决明子蒽醌苷对两肾一夹高血压大鼠心室肌肥厚及舒张功能的影响。方法复制两肾一夹高血压大鼠动物模型,随机分为模型组、0.2、0.4 g/kg决明子蒽醌苷组及佐芬普利(0.01 g/kg)组。另取10只大鼠作为假手术组。各组大鼠灌胃给药8 w。给药后第57天测量大鼠颈动脉平均压(m CAP)、左室舒张末期压(LVEDP)、左室压力最大下降速率(LV-dp/dtmax)及左室质量与胫骨长度比值(LVW/TL)。制备心肌组织匀浆,放免法测定上清液中血管紧张素Ⅱ(AngⅡ)、醛固酮(ALD)及内皮素(ET)含量。结果决明子蒽醌苷能明显抑制两肾一夹高血压大鼠的左心室肥厚,改善心室舒张功能,与模型组比较,LVW/TL、LVEDP值明显降低、LV-dp/dtmax值明显升高(P<0.05或P<0.01),该作用与其抑制心内AngⅡ、ALD及ET表达有关(P<0.05或P<0.01)。结论明子蒽醌苷能抑制肾源性高血压所致心肌肥厚,改善心室舒张功能,且其能够有效降低心脏局部AngⅡ、ALDAET分泌有关。     

芪苈强心胶囊联合缬沙坦对老年慢性舒张性心力衰竭病人心脏舒张功能的影响

目的研究芪苈强心胶囊联合缬沙坦对老年慢性舒张性心力衰竭(CDHF)病人心脏舒张功能的治疗作用。方法选取2015年6月—2017年12月在我院住院治疗的老年CDHF病人100例作为研究对象,采用随机数字表法分为对照组和观察组,每组50例。对照组给予心力衰竭的基本药物治疗;观察组在此基础上联合芪苈强心胶囊和缬沙坦治疗,两组均治疗3个月。观察分析治疗前后左室射血分数(LVEF)、心率(HR)、N端B型钠尿肽前体(NT-proBNP)、6 min步行距离和左室舒张末期内径(LVEDD)、左房容积指数(LAVI)、二尖瓣舒张早期峰值速度(E)与瓣环舒张早期峰值速度(E′)的比值(E/E′)、A峰和E峰流速比值(E/A)。结果观察组总有效率为92%,对照组总有效率为68%,两组比较差异有统计学意义(P0.05);治疗前两组LVEF、HR、NT-proBNP、6 min步行距离和LVEDD、LAVI、E/E′、E/A比较差异无统计学意义(P0.05);两组治疗后均较治疗前改善有统计学意义(P0.05),观察组与对照组相比改善更明显(P0.05)。结论芪苈强心胶囊联合缬沙坦可以有效治疗老年CDHF,改善心脏舒张功能,缓解临床症状。     

培哚普利对大鼠心肌缺血再灌注损伤的影响

目的 观察培哚普利时大鼠心肌缺血再灌注损伤的影响.方法 健康Wistar大鼠20只随机分成两组.培哚普利组结扎冠脉前20 min给予培哚普利2 mg/kg静脉注入;缺血再灌注组给予等量生理盐水静脉注入.测定血流动力学参数,左室收缩压(LVSP)、左室舒张末压(LVEDP)、左室内压最大上升速率( dP/dTmax)及左室内压最大下降速率(-dP/dTmax),光镜观察心肌形态学改变.结果 与缺血再灌注组比较,培哚普利组大鼠LVSP及士dP/dTmax均明显升高(P<0.05或P<0.01);缺血再灌注组大鼠心肌纤维断裂坏死,大量炎性细胞浸润,而培哚普利组无出血、坏死,有少量炎性细胞浸润.结论 心肌缺血再灌注可导致缺血心肌进一步损伤,培哚普利可减少炎性细胞的浸润,对大鼠缺血再灌注损伤心肌有保护作用.     

紫杉醇治疗老年缺血性室性心律失常的临床评价

目的观察紫杉醇治疗老年缺血性心律失常的效果,并探讨其作用机制。方法选取60例冠状动脉粥样硬化性心脏病并发室性心律失常的老年患者,随机分为135 mg/m2紫杉醇组(低剂量组)、155 mg/m2紫杉醇组(高剂量组)。两组均用生理盐水溶解药物,通过静脉给药,每日1次,每2 w停1 w作为1个疗程。经过3个疗程,比较两组治疗前后的左室舒张末内径(LVDD)、舒张末室间隔厚度(IVS)及左室后壁厚度(LVPW)及左室射血分数(LVEF)、心电图的主要差别。结果 135、155 mg/m2紫杉醇均可以降低缺血性室性早搏症状,且呈剂量依赖性,两组比较差异显著(P0.05);相对于治疗前LVDD、IVS、LVPW指标,治疗后这些指标均明显降低(P0.05);而治疗后的LVEF则明显比治疗前升高(P0.01)。结论紫杉醇可以有效预防和控制缺血性室性心律失常,对保护缺血性心脏损伤具有重要作用。     

多巴酚丁胺、米力农干预美托洛尔致心脏负性肌力效应的实验研究

目的观察在美托洛尔使大鼠心脏左室收缩功能减弱后,临床常用正性肌力药物(多巴酚丁胺、米力农)对大鼠心功能的改善作用。方法将Wistar雄性健康大鼠32只,随机分为正常对照组、美托洛尔5 mg/kg组、美托洛尔10 mg/kg组、美托洛尔20 mg/kg组,各8只,观察不同浓度多巴酚丁胺、米力农给药前后各组大鼠心率(HR)、左心室发展压(LVDP)、左室内压上升最大速率(+dp/dt_(max))、左室内压下降最大速率(-dp/dt_(max))等心功能指标变化。结果美托洛尔20 mg/kg组健康大鼠的心率、LVDP、+dp/dt_(max)、-dp/dt_(max)的绝对值明显小于正常对照组(P0.05)。多巴酚丁胺具有明显加快心率的作用,且增大+dp/dt_(max)、-dp/dt_(max)的绝对值,但对健康大鼠LVDP的影响并没有明显增加,多巴酚丁胺的正性变时、正性变力效应明显被美托洛尔减弱,米力农不影响心率,LVDP及+dp/dt_(max)、-dp/dt_(max)的绝对值在正常对照组和美托洛尔各浓度组都有很大的提高。结论米力农可以改善美托洛尔引起的心功能减弱,用多巴酚丁胺则未得到改善。     

氯沙坦联合依那普利对高血压心肌肥厚患者左室舒张功能的影响

目的 观察氯沙坦联合依那普利对高血压心肌肥厚患者左心室舒张功能的影响.方法 采用自身对照设计,36例坚持随访均患者给予氯沙坦50mg/次,每天一次;依那普利10mg/次～20mg/次,每天一次,随访24周,期间比较血压的变化;治疗前后作超声心动图检查,比较心肌厚度及左室舒张功能的改变.结果 与治疗前相比,患者左室后壁舒张末期厚度(LVPWT)、室间隔舒张末期厚度(IVST)、均明显下降(P<0.01);反映左室舒张功能的A/E值亦较治疗前下降(P<0.05);收缩压与舒张压均明显降低(P<0.01). 结论 氯沙坦与依那普利联合用药能有效地控制血压、逆转左室肥厚、改善左心室舒张功能.     

心血管病患者血浆脑钠素与左室舒张功能的关系

目的:探讨左室舒张功能障碍患者血浆脑钠素(BNP)水平变化及其意义。方法:选择左室舒张功能障碍患者60例(患者组)及健康体检者20例(对照组),采用固相免疫放射分析法检测血浆BNP浓度。超声多普勒结合组织多普勒显像(TDI)测定左室结构、左室舒张功能及左室舒张末压。结果:①与对照组相比,患者组BNP浓度升高,左房内径增大、室间隔和左室后壁增厚,差异有统计学意义(P<0.01);但左室内径和左室射血分数差异无统计学意义(P>0.05)。②记录患者组二尖瓣舒张早期最大血流速度(E)与舒张晚期的最大血流速度(A)及其比值,二尖瓣瓣环-室间隔交界处舒张早期的速度峰值(Em间)和二尖瓣瓣环-侧壁交界处舒张早期的速度峰值(Em侧),计算出E/Em间呈E/Em侧,与对照组比较,患者组E/A比值降低、E/Em侧升高(P<0.01)。③患者组血浆BNP浓度与E/Em侧、E/Em间呈正相关(均r=0.29,P<0.05)。结论:左室舒张功能障碍患者BNP浓度明显升高,左室舒张末压升高是刺激BNP分泌的因素。     

曲马多对全身麻醉后寒战的干预治疗效果观察

目的探讨曲马多对全身麻醉后寒战的预防及治疗作用。方法将120例全身麻醉下行腹部手术的患者随机分为A、B、C组和对照组各30例。A组气管插管拔管前30min静注曲马多1mg/kg;B组拔管后静注曲马多0.5mg/kg,间隔10min后再次静注0.5mg/kg;C组拔管后单次静注曲马多1mg/kg;对照组拔管前30min单纯静注生理盐水,量同A组。记录麻醉后2h寒战发生情况。结果 A、B、C组寒战发生率明显低于对照组;A、B组明显低于C组（P均〈0.05）。结论曲马多预防麻醉后寒战安全有效;麻醉结束前预注或者术后小剂量分次静注效果更好。     

利用心脏彩超评估左心室前负荷

目的利用心脏彩超评估左心室前负荷变化对左心收缩舒张功能的影响。方法选取青海红十字医院2014年1月至2014年12月的80例肾功能不全患者进行回顾性研究,根据透析后,体重差异大小分为2组,其中A组差异2.5 kg(35例);B组差异2.5 kg(45例)。在进行1次血液透析前后,分别利用心脏彩超测量所有患者的左室射血分数(LVEF)、舒张早期最大流速(E)、舒张晚期最大流速(A)、E/A、左室舒张末期内径(LVEDD)和左室收缩末期内径(LVESD)。结果 A组患者透析前后各项指标无明显变化,差异无统计学意义(P均0.05)。B组透析后较A组二尖瓣血流频谱E峰明显降低,A峰明显升高,E/A明显降低,差异有统计学意义(P均0.05)。结论心脏彩超评估左心室前负荷对左心收缩舒张功能的影响时,若前负荷变化达到一定程度会明显影响左心舒张功能,而对左心收缩功能无明显影响。     

芪苈强心胶囊与美托洛尔对心力衰竭大鼠心功能及BNP影响的对比研究

目的对比观察芪苈强心(QLQX)胶囊和美托洛尔对心力衰竭大鼠心功能、心室重塑及脑利钠肽(BNP)的影响。方法将饲养4周的44只心肌梗死合并心力衰竭的心衰模型大鼠分成5组:心衰模型组、QLQX胶囊低剂量(0.25 g/kg.d)组、QLQX胶囊高剂量(1.0 g/kg.d)组、美托洛尔(10 mg/kg.d)组、假手术组。灌胃给药,1/日,连续4周后,测心率及超声心动测定左室收缩末内径(LVESD)、左室舒张末内径(LVEDD)、左室射血分数(LVEF)、左室短轴缩短率(LVFS),计算全心质量指数(HW/BW),酶免法测定脑钠肽(BNP)。结果与心衰模型组相比,高剂量QLQX胶囊组和美托洛尔组均可显著性缩小LVESD、LVEDD,升高LVEF、LVFS,(P0.05);高剂量QLQX胶囊组与心力衰竭模型组相比HW/BW和BNP显著性下降,(P0.05)。结论高剂量QLQX胶囊与美托洛尔一样均能改善心衰大鼠的左室功能,并在短期内可显著改善心力衰竭大鼠心肌重塑。     

Differential effects of milrinone and dobutamine on right ventricular preload, afterload and systolic performance in congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy

To compare the effects of intravenous dobutamine and milrinone on right ventricular (RV) systolic function, 14 patients with severe congestive heart failure underwent simultaneous radionuclide-hemodynamic study. Patients were randomized to receive intravenous milrinone (50 micrograms/kg bolus then 0.5 microgram/kg/min) or dobutamine (2.5 to 15 micrograms/kg/min) to achieve equal increases in cardiac output. Both drugs significantly improved cardiac performance, with identical 24% increases in mean cardiac index (p less than 0.05 vs baseline; difference not significant for milrinone vs dobutamine) and no change in heart rate. Neither drug substantially altered RV preload, as reflected by mean right atrial pressure and RV end-diastolic volume. Both drugs caused similar increases in RV ejection fraction (mean +/- standard deviation; dobutamine: 0.32 +/- 0.09 to 0.40 +/- 0.11; p less than 0.05; milrinone: 0.35 +/- 0.19 to 0.43 +/- 0.21; p less than 0.05) resulting from reductions in RV end-systolic volume. RV afterload reduction contributed substantially to drug effect on RV systolic performance in patients treated with milrinone but not those treated with dobutamine. With doses effecting equal increases in cardiac index and RV systolic performance, pulmonary artery end-systolic pressure was significantly reduced by milrinone (40 +/- 12 to 33 +/- 12 mm Hg; p less than 0.05), but not by dobutamine. Thus, in patients with congestive heart failure milrinone's effect on RV systolic function is explainable, at least in part, by RV afterload reduction, whereas RV inotropic augmentation contributed more strongly to dobutamine's effect.     

重组人脑利钠肽与米力农治疗难治性心力衰竭的疗效观察

目的 观察比较重组人脑利钠肽(rhBNP)与米力农治疗难治性心力衰竭(RHF)的临床疗效及安全性.方法 选取RHF患者84例,随机分为两组.观察组使用rhBNP 1.5μg/kg静脉冲击,0.0075μg·kg-1·min-1持续静脉滴注;对照组使用米力农,负荷量50μg/kg,5～10min缓慢静脉滴注,以后0.25～1.00μg·kg-1·min-1维持.每日最大剂量不超过1.13mg/kg.共使用3d,观察疗效及不良反应.结果 观察组治疗有效率明显优于对照组,两组比较差异有统计学意义(P＜0.05).结论 rhBNP治疗RHF疗效确切,较米力农治疗后改善更加显著,安全性更高.     

Acute effects of intravenous furosemide administration on serum digoxin concentration

The effect of intravenous (IV) furosemide (2.5 mg/kg) on serum digoxin concentration, urine flow rate, and myocardial contractility and rhythm was studied in normal dogs and dogs treated with digoxin. Furosemide IV to animals which had not been receiving digoxin resulted in increased urine flow rate from 0.11 ± 0.03 to 0.43 ± 0.1 ml/min/kg, but had no effect on myocardial contractility, blood pressure, or cardiac rhythm. Furosemide IV to animals with steady-state therapeutic serum concentrations of digoxin (2.0 ± 0.58 ng/ml) increased urine flow similarly but did not significantly alter serum digoxin concentration, blood pressure, myocardial contractility, or cardiac rhythm. Thus, contrary to some previous reports, furosemide does not interact with digoxin to produce an elevation in serum digoxin concentration or enhancement of the glycoside's myocardial action.     

Haemodynamic dose-response actions of cicloprolol in left ventricular dysfunction due to ischaemic heart disease

Cicloprolol is a cardioselective beta-1 partial agonist; its haemodynamic and radionuclide (nuclear stethoscope) effects were determined in 22 patients with impaired left ventricular function due to coronary artery disease. Following a 20 min stable control period, the effects of four doses of cicloprolol (0.025, 0.025, 0.05 and 0.1 mg/kg at 10 min intervals) were measured at rest 5-10 min after each intravenous injection. The effects of the cumulative 0.2 mg/kg dosage were assessed during supine bicycle exercise and compared with a control exercise period. At rest there were significant increases in systolic arterial without change in mean blood pressure. The heart rate and cardiac index were unchanged. There was a significant increase in left ventricular ejection fraction with a reduction in filling pressure and volume. Patients with resting heart rate below 75 beats/min and with ejection fraction greater than 35% showed the greatest improvement. During supine bicycle exercise, ejection fraction was increased compared to control (31 +/- 2 to 36 +/- 2; P less than 0.01), cardiac volume reduced and exercise tachycardia attenuated. These data suggest that cicloprolol may be of value where beta-blockade is considered in the presence of underlying left ventricular dysfunction due to ischaemic heart disease.     

Opioid receptor agonists D-Ala-2-Me-Phe-4-Met-(O)-ol enkephalin and ethylketocyclazocine in the brain accentuate digoxin-induced arrhythmias.

OBJECTIVE: To examine the potential effects of two opioid receptor agonists in the brain on digoxin-induced cardiac arrhythmias and to explore cholinergic mechanisms in any potential effect on arrhythmias. METHODS AND RESULTS: Digoxin-induced arrhythmias were produced in guinea pigs (weighing between 280 and 350 g) that received digoxin 50 micrograms/kg intravenous bolus plus digoxin 500 micrograms/kg/h intravenously. Animals received D-Ala-2-Me-Phe-4-Met-(O)-ol enkephalin (FK 33,824) (50 or 100 micrograms/kg), ethylketocyclazocine (EKC) (50, 10 or 1 micrograms/kg) or saline (control) into the lateral cerebroventricle prior to digoxin. FK 33,824 produced significant (P less than 0.05) dose-dependent reductions in the threshold for digoxin-induced arrhythmias. The mean digoxin dosage at the development of fatal arrhythmias after the 100 micrograms/kg of FK 33,824 was 30% lower than the control group. EKC also produced significant (P less than 0.05) dose-dependent reductions in the threshold for digoxin-induced arrhythmias and the mean dose at development of fatal arrhythmias was 67% lower than the control group after 50 micrograms/kg of EKC. In the absence of digoxin, the highest dosages of each of these opioids did not produce arrhythmias. Changes in blood pressure and heart rate were unlikely explanations for the observed actions of these opioids because D-Ala-2-Me-Phe-4-Met-(O)-ol enkephalin accentuated the increase in blood pressure that accompanied digoxin while EKC reduced the blood pressure response to digoxin and neither altered the heart rate response to digoxin. In the control group, fatal digoxin-induced arrhythmias were ventricular tachyarrhythmias in two-thirds of cases and complete heart block in the remainder. These opioids accentuated the development of complete heart block. The role of the cholinergic system was explored for only EKC because both opioids produce similar effects on arrhythmias, using atropine sulphate which crosses the blood brain-barrier and atropine methylnitrate which does not enter the central nervous system. Atropine sulphate, but not atropine methylnitrate, slightly blunted but did not reverse the action of EKC. CONCLUSIONS: These data indicate that: two opioids in the brain--D-Ala-2-Me-Phe-4-Met-(O)-ol enkephalin and EKC--alter the threshold for development of digoxin-induced arrhythmias, specifically accentuating development of complete heart block produced by digoxin; and cholinergic mechanisms play only a small role in modulating the action of EKC on digoxin-induced bradyarrhythmias.     

Cardiotonic activity of a new inotropic agent, 3,4-dihydro-6-[4-(3,4-dimethoxybenzoyl)-1-piperazinyl]-2(1H)- quinolinone (OPC-8212), in the dog with and without beta-blocker and Ca++-antagonist pretreatment

Hemodynamic effects of a new inotropic agent, OPC-8212 (2(1H)-quinolinone derivative) were studied in anesthetized open chest dogs pretreated with propranolol and diltiazem. Three doses (1, 3 and 10 mg/kg) of OPC-8212 were administered intravenously and the net hemodynamic effect (% change) was obtained by subtraction of the effect of the solvent from the gross effect, since the vehicle has a transient, but significant hemodynamic effect. The maximal inotropic effect occurred 3 minutes after administration: LV dP/dt max and cardiac output (CO) increased by 19 +/- 2.5% and 28 +/- 8.5%, respectively, at 3 mg/kg. These cardiotonic effects were dose-dependent, whereas heart rate, peak LV pressure (PLVP) and mean aortic pressure were minimally changed at any dose. Accordingly, systemic vascular resistance (SVR) decreased in a dose-dependent manner although the decrease was much less than that in administration of isoproterenol. The inotropic effect was not blocked by beta-adrenoceptor blockade (propranolol 1 mg/kg), indicating that the cardiotonic action of this agent is not due to beta-adrenergic stimulation. Thus, this agent could reverse beta-blocker-induced heart failure. During infusion of diltiazem (0.1 mg/kg/min following bolus intravenous administration of 0.5 mg/kg), the increases in LV dP/dt max and CO due to OPC-8212 were similar to those in the control study. In contrast to the effects under beta-adrenoceptor blockade, however, decreased PLVP was restored by OPC-8212. Neither chronotropic nor rrhythmogenic effects were observed in the control or with either pharmacological intervention. These results indicate that OPC-8212 has a potent inotropic action with modest vasodilatory effect even with propranolol or diltiazem pretreatment.(ABSTRACT TRUNCATED AT 250 WORDS)     

Immediate effects of milrinone on metabolic and sympathetic responses to exercise in severe congestive heart failure

A randomized, double-blind, placebo-controlled protocol was used to determine whether milrinone exerts an immediate effect on exercise performance in patients with severe congestive heart failure. In each of 14 patients with New York Heart Association class III or IV congestive heart failure, intravenous milrinone (mean 57 +/- 5 micrograms/kg) and placebo were randomly administered just before maximal progressive upright cycle ergometry. The duration of exercise was significantly longer with milrinone than with placebo treatment (placebo 11.0 +/- 0.6 minutes, milrinone 12.5 +/- 0.9 minutes, p = 0.01). Compared with placebo, milrinone caused a higher peak oxygen uptake (placebo 10.8 +/- 0.6 ml/kg/min, milrinone 12.4 +/- 0.7 ml/kg/min, p = 0.001) and oxygen uptake at the anaerobic threshold (placebo 7.8 +/- 0.4 ml/kg/min, milrinone 9.2 +/- 0.4 ml/kg/min, p = 0.001). At peak exercise intensity, systolic blood pressure (placebo 119 +/- 5 mm Hg, milrinone 131 +/- 5 mm Hg, p = 0.001) and heart rate (placebo 114 +/- 5 beats/min, milrinone 126 +/- 6 beats/min, p = 0.001) were both increased with milrinone. Likewise, at matched submaximal exercise intensities, heart rate (placebo 111 +/- 19 beats/min, milrinone 117 +/- 20 beats/min, p less than 0.05) and systolic blood pressure (placebo 116 +/- 19 mm Hg, milrinone 121 +/- 19 mm Hg, p = 0.04) were higher with milrinone; plasma norepinephrine (placebo 1,692 +/- 208 ng/liter, milrinone 1,320 +/- 216 ng/liter, p = 0.05) and blood lactate concentrations (placebo 2.2 +/- 0.2 mM, milrinone 1.9 +/- 0.2 mM, p less than 0.05) were lower.(ABSTRACT TRUNCATED AT 250 WORDS)     

Long-term use of K-strophanthin in advanced congestive heart failure due to dilated cardiomyopathy: A double-blind crossover evaluation versus digoxin

K-strophanthin or digoxin were added to diuretics (all cases) and vasodilators (most cases) for treating advanced congestive heart failure in 22 patients with dilated cardiomyopathy and sinus rhythm. K-strophanthin (0.125 mg intravenously) or digoxin (0.25 mg orally) were administered daily in two 3-month periods, during which vasodilators and diuretics were kept constant and patients received one of the two digitalis preparations in a double-blind fashion, crossing over to, the alternative preparation in the next period. Blindness was assured throughout the trial with a daily intravenous injection of 10 ml normal saline solution either containing K-strophanthin or not, and with daily oral administration of either placebo or active digoxin. At the end of the run-in period, 15 days after starting active preparations, and thereafter every month for the next 6 months, we evaluated left ventricular pump function at rest and patients' functional performance by a cardiopulmonary exercise test. At Day 15, cardiac index and ejection fraction at rest, compared with run-in, were significantly raised with both glycosides; during exercise while on K-strophanthin, peak oxygen consumption was augmented by 1.4 ml/min/kg (p < 0.01) and oxygen consumption at anaerobic threshold by 2.2 ml/ min/kg (p < 0.01); corresponding variations on digoxin (0.1 and +0.3, respectively) were not significant versus run-in. These patterns were duplicated at repeated tests during follow-up. In the entire population Means for oxygen consumption at peak exercise and at anaerobic threshold were raised from run-in values by 1.4 (p < 0.01) and 2.2 ml/min/kg (p < 0.01), respectively, after 3 months of K-strophanthin treatment, and by 0.0 and 0.1 ml/min/kg, respectively, after treatment with digoxin for the same period of time. Results were similar in nine patients when they were given digoxin intravenously (0.25 mg/day) for 1 week after having completed the trial with the oral digoxin preparation. These results indicate that K-strophanthin improved functional performance in patients with severe cardiac decompensation due to dilated cardiomyopathy; digoxin failed to provide the same results, independent of the drug sequence or the route of administration. The reasons for these differences are basically unknown and do not seem to be related only to changes in cardiac performance at rest, because both K-strophanthin and digoxin significantly and persistently raised cardiac output and ejection fraction at rest.     

Pharmacodynamic effects of milrinone with and without a bolus loading infusion

BACKGROUND: Milrinone is a positive inotropic agent with vasodilatory and lusitropic activity. Milrinone dosed as a 50 microg/kg bolus followed by a continuous infusion provides an immediate and sustained hemodynamic response. The comparative pharmacodynamics of a placebo bolus and a milrinone bolus followed by a continuous milrinone infusion in patients with decompensated heart failure are unknown. METHODS: Nineteen patients with decompensated heart failure underwent right heart catheterization and were randomized to receive an intravenous infusion of milrinone at a rate of 0.50 microg/kg/min with (n = 9) or without (n = 10) a preceding 50 microg/kg bolus. Pulmonary capillary wedge pressure, cardiac index, and plasma milrinone levels were measured serially over 24 hours. RESULTS: In the milrinone bolus group, maximal effects on plasma concentration (352.3 ng/mL), cardiac index (+0.97 L/min/m(2), P =.02), and pulmonary capillary wedge pressure (-11.25 mm Hg, P <.001) were seen after the loading dose. In the placebo loading dose group, significant hemodynamic effects were observed starting at 30 minutes after the start of the continuous infusion. Changes in pulmonary capillary wedge pressure (placebo -8.6 vs milrinone -8.78 mm Hg, P not significant [NS]) were similar in both groups at 2 hours, whereas changes in cardiac index (placebo loading +0.81 vs milrinone loading +0.78 L/min/m(2), P NS) and milrinone levels (placebo loading 168.0 vs milrinone loading 165.6 ng/mL, P NS) were similar at 3 hours. One patient randomized to a milrinone bolus demonstrated a marked decrease in blood pressure and was discontinued from therapy. CONCLUSIONS: A milrinone infusion without a bolus appears to be a rapidly effective inotropic strategy that may have an improved safety profile during the initiation of therapy compared with a continuous infusion strategy initiated with a bolus.     

Pharmacokinetics and pharmacodynamics of milrinone in chronic congestive heart failure

The acute hemodynamic effects and pharmacokinetics of bolus intravenous milrinone administration were assessed in 13 patients with severe congestive heart failure. Serial hemodynamics were measured and blood samples were obtained to determine plasma milrinone concentration and calculation of pharmacokinetic variables after administration of milrinone at 12.5, 25, 50 and 75 micrograms/kg, allowing at least 6 hours to elapse between consecutive milrinone doses. At each dose milrinone effected prompt but very short-lived increases in cardiac output and left ventricular stroke work and decreases in pulmonary artery pressure, right atrial pressure and systemic and pulmonary vascular resistance in a non-dose-dependent fashion. Pulmonary artery wedge pressure decreased in a dose-related manner. Heart rate increased significantly after the 75-micrograms/kg dose and mean arterial pressure decreased significantly only after the 50- and 75-micrograms/kg milrinone dose. The time-dependent decline in plasma milrinone concentration was biexponential and log linear, conforming to an open 2-compartment model of drug distribution and elimination. Mean plasma milrinone clearance (+/- standard error) was 0.15 +/- 0.03 liters/min/kg, volume of distribution was 0.35 +/- 0.02 liters/kg and mean elimination half-life was 1.7 hours.