尼可地尔对急性心肌梗塞患者血流动力学的影响

11例急性心肌梗塞患者(男10女1,年龄62±SD9 yr)于发病3d内入院,用尼可地尔15-20mgpo,监测服药前、后的血流动力学变化,结果显示服用尼可地尔后心率减慢,血压、右心房压、肺楔嵌压、体循环及全肺阻力下降,心脏指数增加(P<0.05);药物作用于服药后1-2h最明显,4h仍有作用。示该药可改善患者的血流动力学指数。     

Hemodynamic response to ibopamine in acute myocardial infarction

To determine the effects of ibopamine on hemodynamic parameters, 9 patients with cardiac dilation after acute myocardial infarction were studied. Although there were no significant changes in mean blood pressure, heart rate and rate pressure product after administration of ibopamine, cardiac index and urine volume increased significantly. These data indicate that ibopamine exerts a positive inotropic effect on the myocardium and vasodilating effect on renal vasculature without increasing myocardial oxygen consumption. However, pulmonary capillary wedge pressure increased significantly at 30 min after ibopamine and decreased to the control value at 120 min. A significant increase in heart rate was observed in 3 patients which was followed by chest pain. In addition to increase in cardiac contractile force and decrease in subendocardial perfusion from elevated left ventricular end diastolic pressure, increase in heart rate would decrease diastole time, while increase in oxygen consumption results in aggravation of ischemia especially in patients with multivessel coronary disease. From these findings it is considered that ibopamine should be administered with care to patients with multivessel coronary disease.     

Pharmacokinetics and haemodynamic effects of tocainide in patients with acute myocardial infarction complicated by left ventricular failure.

The pharmacokinetics and haemodynamic effects of tocainide, an orally active structural analogue of lignocaine, were studied in patients with acute myocardial infarction complicated by left ventricular failure. Fourteen patients (mean age 65 years) with acute myocardial infarction complicated by mild left ventricular failure were studied, following a single dose of tocainide (250 mg) by intravenous infusion, over 30 min. Heart rate, systemic arterial pressure, pulmonary artery pressure and cardiac output were monitored. Plasma tocainide levels were estimated by gas chromatography. The mean plasma level of tocainide achieved was 2.95 micrograms/ml (15.37 mmol/l). The mean plasma half-life was 15.6 h. The mean cardiac index was reduced 5 min after completion of the infusion, from 2.24 1 min-1 m-2 (+/- 0.40) to 2.07 1 min-1 m-2 (+/- 0.29) (P less than 0.01). At 90 min the cardiac index had returned to pre-treatment levels. Small changes were seen in the heart rate, arterial blood pressure and the pulmonary artery pressure but these changes were not statistically significant. The pharmacokinetics of tocainide were not significantly altered in patients with acute myocardial infarction complicated by mild left ventricular failure.     

琥珀酸美托洛尔缓释片和酒石酸美托洛尔片对急性心肌梗死患者心率的影响

目的比较琥珀酸美托洛尔缓释片和酒石酸美托洛尔片对急性心肌梗死患者心率的影响。方法选择急性心肌梗死患者76例,在除外应用美托洛尔禁忌后,按1∶2比例随机分配到琥珀酸美托洛尔缓释片组25例和酒石酸美托洛尔片组51例。前者给予琥珀酸美托洛尔23.75 mg,日1次口服,后者给予酒石酸美托洛尔12.5 mg,日2次口服。在此基础上,两组均常规予阿司匹林、氯吡格雷、ACEI及他汀类药物治疗,分别记录用药前和用药后24、48、72 h静息状态的心率,比较用药后心率下降的程度和趋势。结果琥珀酸美托洛尔缓释片组在用药后24、48、72 h 3个时间点的心率分别下降了0、1%、9%,次数下降了0.5次/min、1.6次/min、7.6次/min,酒石酸美托洛尔片组心率分别下降了3%、5%、6%,次数下降了3.5次/min、4.1次/min、5.7次/min。P均<0.05,认为不同时间点上患者心率的差异有统计学意义;而因素心率和剂型的交互作用的P值均>0.05,尚不能认为剂型和心率有交互作用。两组患者服药后72 h内,心率变化的趋势无统计学意义,P均>0.05。结论急性心肌梗死患者应用琥珀酸美托洛尔缓释片或酒石酸美托洛尔片,72 h内心率降低的差异有统计学意义,但两组服药后72 h内,心率的降低程度差异无统计学意义,而且72 h内两组心率下降的趋势,差异也无统计学意义。     

美托洛尔对急性心肌梗死QT离散度及恶性心律失常的影响

目的 探讨美托洛尔对急性心肌梗死(AMI)后QT间期离散度(QTcd)及恶性心律失常(MVA)事件的影响。方法 将88例分为美托洛尔组(46例)及对照组(42例)。美托洛尔组在常规治疗基础上给予美托洛尔6.24-12.50mg,2次/d,以后根据病情渐加量到25-50mg,2次/d;对照组仅常规治疗,分别测定入院后第1天、第7天及0.5年、1年时24h动态心电图及12导联心电图,常规进行QTcd分析,并同时观察各阶段MVA发生率。结果 1周内两组QTcd及MVA变化无显著性差异,但美托洛尔组MVA事件有减少趋势,0.5年后美托洛尔组QTcd显著改善(P<0.01),MVA事件发生率明显低于对照组(P<0.01)。结论 美托洛尔能有效改善AMI后患者QTcd,降低MVA发生率,但此种改变在长时间治疗后明显。     

替罗非班联合美托洛尔治疗急性心肌梗死的疗效观察

目的 探讨替罗非班联合美托洛尔治疗心肌梗死患者的临床效果.方法 选取2017年6月—2019年6月在周口豫东医院治疗的心肌梗死患者118例,随机分为对照组和治疗组,每组各59例.对照组患者口服酒石酸美托洛尔片,前期剂量6.25 mg/次,2～3次/d,根据患者病情增加药量,每次增加6.25～12.5 mg,最大剂量50...     

Prophylaxis against ventricular arrhythmias in suspected acute myocardial infarction: a comparison of tocainide and disopyramide.

Five hundred and seventy one patients admitted to a coronary care unit with suspected acute myocardial infarction were considered for entry into a double-blind study. Two hundred and eighty-three patients were excluded, mainly because of recent treatment with beta-adrenoceptor blocking agents, life threatening arrhythmias requiring specific treatment and left ventricular failure presenting with hypotension or pulmonary oedema. Two hundred and eighty-eight entered the trial of whom 202 were subsequently confirmed to have had myocardial infarction. The effects of tocainide and disopyramide on ventricular arrhythmias were compared with placebo over the first 48 h period. The three treatments were given by a combination of intravenous infusion and oral administration. The doses used were tocainide 500 mg intravenously over 30 min plus 2800 mg orally over 48 h and disopyramide 150 mg intravenously over 30 min plus 1050 mg orally over 48 h. As judged by counts of ventricular premature beats, tocainide and disopyramide exerted a similar and significant antiarrhythmic effect. The median number of ventricular premature beats over the first 24 h of treatment was 58 on placebo compared with 30 on tocainide (P less than 0.05) and 19 on disopyramide (P less than 0.05). The corresponding figures for the second 24 h were 9, 6 and 2, respectively. There were eight deaths and three episodes of ventricular fibrillation with no significant differences between the three treatment groups. Sustained ventricular tachycardia was observed in one patient in the tocainide group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hemodynamic and endocrine effects of acute and chronic administration of nifedipine

Although it is well known that calcium channel blockers can influence contraction of vascular smooth muscle, there is less knowledge on its effect on excitation contraction coupling in the endocrine glands and more specifically on insulin and glucagon release. In this study, nifedipine was administered in doses of 40 to 80 mg/day to 14 patients with essential hypertension, and its hemodynamic effects were evaluated by non-invasive methods, and its effect on glucose metabolism by an arginine infusion test. Nifedipine produced a significant reduction in systolic and diastolic blood pressure, both after the first dose (30/12 mm Hg) and after 8 weeks of administration (19/12 mm Hg). There were no significant changes in cardiac output (5.1 to 4.9 L/min), muscle (2.4 to 3.2 mL/sec/min) or cutaneous basal flow (9.8 to 8.6 mL/100 mL) as measured non-invasively by echocardiogram and by plethysmography. Insulin and glucagon release were evaluated by the arginine infusion test. Nifedipine produced a tendency towards an increase in glucagon release and a reduction in insulin release although these changes did not reach statistical significance. In this group of patients, nifedipine produced a significant reduction in systolic and diastolic pressure, but no significant changes in insulin or glucagon plasma levels.     

Hemodynamic and endocrine effects of acute and chronic administration of nifedipine

Although it is well known that calcium channel blockers can influence contraction of vascular smooth muscle, there is less knowledge on its effect on excitation contraction coupling in the endocrine glands and more specifically on insulin and glucagon release. In this study, nifedipine was administered in doses of 40 to 80 mg/day to 14 patients with essential hypertension, and its hemodynamic effects were evaluated by non-invasive methods, and its effect on glucose metabolism by an arginine infusion test. Nifedipine produced a significant reduction in systolic and diastolic blood pressure, both after the first dose (30/12 mm Hg) and after 8 weeks of administration (19/12 mm Hg). There were no significant changes in cardiac output (5.1 to 4.9 L/min), muscle (2.4 to 3.2 mL/sec/min) or cutaneous basal flow (9.8 to 8.6 mL/100 mL) as measured non-invasively by echocardiogram and by plethysmography. Insulin and glucagon release were evaluated by the arginine infusion test. Nifedipine produced a tendency toward an increase in glucagon release and a reduction in insulin release although these changes did not reach statistical significance. In this group of patients, nifedipine produced a significant reduction in systolic and diastolic pressure, but no significant changes in insulin or glucagon plasma levels.     

Antiarrhythmic effects of stirocainide in acute myocardial infarction

Ventricular arrhythmias, especially ventricular fibrillation, are assumed to be a main cause of sudden death during the first 24 h of acute myocardial infarction. Effective prophylaxis and acute suppression of these life-threatening rhythm disturbances are a major therapeutic problem. The present study was undertaken to investigate the efficacy of the new antiarrhythmic compound stirocainide (2-(1-benzylidene)cycloheptenimino-oxyethyl-diisopropylamine -2-butenedionate, Th 494) in suppressing "2nd phase arrhythmias" arising from large anteroseptal myocardial infarctions using a standardized experimental canine preparation. Our results demonstrate that "2nd phase arrhythmias"--i.e. frequent ventricular ectopics, tachycardias, salvos, and R-on-T phenomena--are reduced by 80-90% (sometimes even completely abolished) by stirocainide (dose: 4 mg/kg within 3 min, followed by 300 micrograms/kg X min over a 20-min period). The administration of the drug at the dose used does not produce severe cardiodepression, but intraventricular conduction time is significantly prolonged. Thus, Th 494 is a highly effective antiarrhythmic agent in acute myocardial infarction, and further experimental and clinical investigations on its antiarrhythmic and antifibrillatory properties may lead to beneficial therapeutic results.     

卡维地洛与美托洛尔在犬急性心肌梗死晚期再灌注中的心肌保护作用的比较

目的探讨卡维地洛在犬急性心肌梗死(AM I)晚期再灌注中的心肌保护作用及其与美托洛尔的比较。方法18条健康成年杂种犬随机平均分为3组:单纯晚期再灌注组(late reperfusion group,LR)、晚期再灌注预加美托洛尔组(late reperfusion+m etoprolol group,LR+M)、晚期再灌注预加卡维地洛组(late reperfusion+carved ilol group,LR+C)。分别灌服生理盐水、美托洛尔(1 mg.kg-1.d-1)、卡维地洛(1 mg.kg-1.d-1)共7 d。所有犬于d 7灌药2 h后开胸结扎左冠状动脉前降支(距离起点5 mm)6 h,再灌注6 h,制成AM I晚期再灌注模型。后处死取左室心肌梗死边缘区,比色法测定心肌超氧生物歧化酶(SOD)和还原性谷胱甘肽酶(GR)活性、丙二醛(MDA)含量,免疫组化法检测心肌Fas和FasL蛋白表达,TUNEL法测心肌细胞凋亡指数(AI)。结果与LR相比,LR+M的SOD、GR活性以及MDA含量无改变(P>0.05),而LR+C的SOD、GR活性均升高(P<0.01),MDA含量降低(P<0.05);进一步研究发现与LR相比,梗死边缘区心肌Fas和FasL蛋白表达以及细胞AI在LR+M明显下降,差异有显著性(P<0.05),并且LR+C比LR+M亦下降明显,两组相比差异有显著性(P<0.05)。结论卡维地洛和美托洛尔对急性心肌梗死晚期再灌注造成的损伤都有保护作用,但卡维地洛的保护作用优于美托洛尔,可能与其抗氧化作用有关。     

Hemodynamic and antiadrenergic effects of dronedarone and amiodarone in animals with a healed myocardial infarction

The hemodynamic and antiadrenergic effects of dronedarone, a noniodinated compound structurally related to amiodarone, were compared with those of amiodarone after prolonged oral administration, both at rest and during sympathetic stimulation in conscious dogs with a healed myocardial infarction. All dogs (n = 6) randomly received orally dronedarone (10 and 30 mg/kg), amiodarone (10 and 30 mg/kg), and placebo twice daily for 7 days, with a 3-week washout between consecutive treatments. Heart rate (HR), mean arterial pressure (MBP), positive rate of increase of left ventricular pressure (+LVdP/dt), echocardiographically assessed left ventricular ejection fraction (LVEF), and fractional shortening (FS), as well as chronotropic response to isoproterenol and exercise-induced sympathetic stimulation were evaluated under baseline and posttreatment conditions. Resting values of LVEF, FS, +LVdP/dt, and MBP remained unchanged whatever the drug and the dosing regimen, whereas resting HR was significantly and dose-dependently lowered after dronedarone and to a lesser extent after amiodarone. Both dronedarone and amiodarone significantly reduced the exercise-induced tachycardia and, at the highest dose, decreased the isoproterenol-induced tachycardia. Thus, dronedarone and amiodarone displayed a similar level of antiadrenergic effect and did not impair the resting left ventricular function. Consequently, dronedarone might be particularly suitable for the treatment and prevention of various clinical arrhythmias, without compromising the left ventricular function.     

Inhibition of metoprolol metabolism and potentiation of its effects by paroxetine in routinely treated patients with acute myocardial infarction (AMI)

Objective To investigate the influence of paroxetine on metoprolol concentrations and its effect in patients treated for acute myocardial infarction (AMI) who are routinely given paroxetine as a co-treatment of depression. Methods We recruited 17 depressed AMI patients who received metoprolol as a routine part of their therapy (mean dose 75 ± 39 mg/day). Patients were genotyped for CYP2D6 *3, *4 and gene duplication. Metoprolol and α-hydroxy-metoprolol were analyzed in plasma 0, 2, 6 and 12 h post-dose. Heart rates (HR) at rest were registered after each sampling. Paroxetine 20 mg daily was then administered, and all measurements were repeated on day 8. Results All patients were genotypically extensive metabolizers (EMs) (nine with *1/*1 and eight with *1/*3 or *4). Following the administration of paroxetine, mean metoprolol areas under the concentration–time curve (AUC) increased (1064 ± 1213 to 4476 ± 2821 nM × h/mg per kg, P = 0.0001), while metabolite AUCs decreased (1492 ± 872 to 348 ± 279 n M × h/mg per kg, P < 0.0001), with an increase of metabolic ratios (MR) (0.9 ± 1.3 to 26 ± 29; P < 0.0001). Mean HRs were significantly lower after the study week at each time point. Mean area under the HR versus time curve (AUEC) decreased (835 ± 88 to 728 ± 84 beats × h/min; P = 0.0007). Metoprolol AUCs correlated with patients’ AUECs at the baseline (Spearman r  = −0.64, P < 0.01), but not on the eighth day of the study. A reduction of metoprolol dose was required in two patients due to excessive bradycardia and severe orthostatic hypotension. No other adverse effects of the drugs were identified. Conclusion A pronounced inhibition of metoprolol metabolism by paroxetine was observed in AMI patients, but without serious adverse effects. We suggest, however, that the metoprolol dose is controlled upon initiation and withdrawal of paroxetine.     

门冬氨酸钾镁在急性心肌梗死早期的临床应用

目的 评价门冬氨酸钾镁在急性心肌梗死（AMI）早期治疗的临床疗效和安全性。方法 在AMI静脉溶栓加常规治疗的基础上，治疗组（70例）给予门冬氨酸钾镁治疗，对照组（66例）不用门冬氨酸钾镁治疗，观察其对溶栓治疗中AMI病死率和严重心律失常发生率的影响。结果 治疗组病死率低于对照组（P＜0．05），治疗组严重心律失常发生率低于对照组（P＜0．05）。结论 门冬氨酸钾镁在AMI早期应用可明显改善预后，门冬氨酸钾镁可作为AMI的常规用药。     

Proarrhythmic effects of procainamide and tocainide in a canine infarction model.

A canine model of myocardial infarction (MI) was used to study the type and frequency of ventricular antiarrhythmic and proarrhythmic effects due to procainamide and tocainide and the risk factors associated with development of proarrhythmia. An anterior MI was created by a 2-h occlusion of the left anterior descending artery (LAD) with complete reperfusion. Programmed ventricular stimulation was performed on two occasions after MI, on days 4-6 and on days 8-10, before drug and during antiarrhythmic drug infusion at three dose levels. The antiarrhythmic drugs were given in a randomized cross-over design. Only procainamide caused a dose-dependent increase in QRS, JTc, and right ventricular effective refractory period (ERP). Neither procainamide nor tocainide made sustained ventricular tachycardia (VT) noninducible, but procainamide slowed the tachycardia rate. Both drugs successfully made ventricular fibrillation (VF) noninducible: procainamide in 78% of trials and tocainide in 50% of trials. Proarrhythmia (development of inducible VT during drug when not present before drug or inability to terminate VT during drug administration) developed in 29% of dogs that received procainamide and 25% of dogs that received tocainide. There was no apparent correlation of QRS, JTc, and right ventricular ERP after drugs and proarrhythmia due to procainamide or tocainide. There was no significant difference in the size of MI between dogs with one or more proarrhythmic response to either drug and dogs that had no proarrhythmia. In this model, procainamide and tocainide had no antiarrhythmic efficacy for VT, but had moderate proarrhythmia potential that was unpredictable.     

The appropriate dosage regime for the transition from intravenous lignocaine to oral tocainide after acute myocardial infarction

Summary To define the appropriate regime for the transition from intravenous lignocaine to oral tocainide after uncomplicated acute myocardial infarction, 43 patients received lignocaine to steady state. Each patient then received a tocainide dosage schedule. Plasma concentration of lignocaine and tocainide was measured frequently until the third peak plasma tocainide level. Tocainide 400 mg 8 hourly starting 4 h before cessation of lignocaine and tocainide 400 mg 4 hourly starting at the end of the infusion produced therapeutic plasma tocainide concentration (3.5–9 mg/l) only after the second dose. Tocainide 600 mg 12 hourly starting 6 h before cessation of lignocaine and tocainide 600 mg 6 hourly starting at the end of the infusion quickly achieved therapeutic plasma tocainide concentration which declined to give subtherapeutic first dose troughs of 2.42 mg/l (±0.28 SEM) and 2.79 mg/l (±0.27 SEM) respectively. Consistently therapeutic plasma tocainide concentrations were achieved by both of these regimes after the second dose. The short plasma halflife of lignocaine which for these regimes was 3.71 h (±0.25 SEM), resulted in subtherapeutic lignocaine concentrations before consistently therapeutic plasma tocainide concentrations had been achieved. On the basis of these results, the 600 mg 6 hourly tocainide dosage schedule was studied with cessation of lignocaine infusion either two or six h after the first tocainide dose. With the former regime only three of 5 patients had therapeutic lignocaine at the subtherapeutic tocainide trough. When lignocaine was discontinued on administration of the second tocainide dose however, therapeutic lignocaine concentration was maintained in all patients until tocainide was rising within the therapeutic range. The latter regime, which we would recommend, was not accompanied by increased side effects. Steady state tocainide was found to be present 12 h after the third tocainide dose allowing continued therapy with tocainide 600 mg 12 hourly.