A double-blind trial of metoprolol in acute myocardial infarction. Effects on ventricular tachyarrhythmias

During a double-blind trial in which patients with suspected myocardial infarction received metoprolol or placebo, we analyzed the occurrence of ventricular tachyarrhythmias. Metoprolol (15 mg intravenously) was given as soon as possible after admission, and thereafter 200 mg was given daily for three months. Antiarrhythmic drugs were given only for ventricular fibrillation and sustained ventricular tachycardia (greater than 60 beats per second). Definite acute myocardial infarction developed in 809 of the 1395 participants, and probable infarction in 162. Metoprolol did not influence the occurrence of premature ventricular contractions or short bursts of ventricular tachycardia. However, there were 17 cases of ventricular fibrillation in the placebo group (697 patients) and only 6 in the metoprolol group (698 patients, P less than 0.05). During the hospital stay significantly fewer patients receiving metoprolol (16) than placebo (38) (P less than 0.01) required lidocaine. In a separate analysis of 145 patients, metoprolol did not influence the occurrence of premature ventricular contractions or short bursts of ventricular tachycardia during the first 24 hours of treatment. Despite a lack of effect on less serious ventricular tachyarrhythmias, metoprolol had a prophylactic effect against ventricular fibrillation in acute myocardial infarction.     

Justification for intravenous magnesium therapy in acute myocardial infarction

Recent studies have shown that patients with acute myocardial infarction (AMI) are magnesium-deficient and develop an additional transient decrease in serum magnesium concentrations (S-Mg c) during the acute phase of the infarct. Animal experiments, as well as studies on humans, have indicated that the acute decrease in S-Mg c as well as a more chronic magnesium (Mg) deficiency state are harmful to the myocardium in the setting of acute ischaemia. This knowledge has led during the last couple of years to the performance of four double-blind placebo controlled studies in which the effect of i.v. magnesium therapy on mortality and incidence of arrhythmias in patients with AMI has been evaluated. Magnesium treatment more than halved the acute mortality and incidence of arrhythmias requiring treatment in three of the four intervention studies. The mechanisms behind the beneficial effect of magnesium therapy are probably multifactorial; a direct depressive effect on the cardiac conducting system; a peripheral dilatory effect on the arteries, reducing the afterload on the myocardium; a reduced infarct size; an ion-stabilizing effect, maintaining stable intra and extracellular concentrations of potassium, sodium and calcium; an improved energy generation in the myocardium; and an inhibitory effect on platelet aggregation. No side-effects were observed in any of the clinical intervention studies. Against this background, the author suggests that i.v. magnesium treatment should be adopted as part of routine practice for patients with acute myocardial infarction.     

Supraventricular tachyarrhythmias in acute myocardial infarction

Onset of atrial tachycardia, flutter or fibrillation occurred in 11% of 274 consecutive patients with acute myocardial infarction (AMI). Atrial tachycardia started about 24 hours and atrial flutter/fibrillation about 72 hours after onset of AMI symptoms. Left heart failure, diagnosed as pulmonary rales or frank pulmonary edema, was not more common in these patients before onset of tachyarrhythmias than among the rest of the patients. On the other hand, a notching of the P wave in lead CR-was significantly more common in the patients with atrial fibrillation (67%). In most of these cases the terminal P force in lead CR1 was not negative as in so-called left atrial enlargement. These findings suggest that atrial conduction disturbances might be a basis of atrial fibrillation in AMI.     

Effect of intravenous streptokinase on left ventricular function and early survival after acute myocardial infarction

In a double-blind trial of streptokinase for acute myocardial infarction, 219 consecutive patients presenting with infarction within four hours (mean, 3.0 +/- 0.8) of the onset of chest pain were randomly assigned to treatment with streptokinase (1.5 million units) or placebo, given intravenously over 30 minutes. The primary end point of the study was left ventricular function in patients with first infarctions. Patients who could undergo beta-blockade also received intravenous propranolol. Heparin (for 48 hours) and a combination of low-dose aspirin and dipyridamole were administered to both groups until cineangiography was performed at three weeks. In the patients with first infarctions treated with streptokinase, the left ventricular ejection fraction was 6 percentage points higher (streptokinase vs. placebo, 59 +/- 10.5 vs. 53 +/- 13.5 percent; P less than 0.005), with benefit to patients with either anterior infarction (57 +/- 11.9 vs. 49 +/- 15.9 percent; P less than 0.05) or inferior infarction (60 +/- 9.1 vs. 55 +/- 11.3 percent; P less than 0.05). Left ventricular function was improved regardless of whether concomitant propranolol was given. Survival (at 30 days) was improved with streptokinase: 2 deaths occurred among 79 patients who received this drug, as compared with 12 deaths among 93 patients who received placebo (2.5 vs. 12.9 percent, P = 0.012). Rates of reinfarction (streptokinase vs. placebo, 3 vs. 1 percent) and requirements for surgery or angioplasty (7 vs. 5 percent) were similar in the two groups. We conclude that administration of intravenous streptokinase (1.5 million units) to patients with a first myocardial infarction results in improved left ventricular function and short-term survival.     

Massive doses of procainamide for ventricular tachyarrhythmias due to myocardial infarction

Three patients are described in whom malignant ventricular arrhythmias appeared in connection with a reinfarction some days after hospitalization for an acute myocardial infarction and in whom massive doses of procainamide, up to 7.5 g/day i.v., were necessary to prevent these arrhythmias. The serum concentration of procainamide was 2--4 times higher than the recommended upper level, but no side-effects were observed. With the dose given, one would have expected still higher serum concentrations. Several reasons for this finding are discussed, including the effects of renal function, intestinal leakage, storage of the drug in tissues and hitherto unknown metabolic pathways of procainamide in patients, who are slow acetylators.     

Serum-ionised magnesium in patients with acute myocardial infarction. Relation to cardiac arrhythmias, left ventricular function and mortality.

Measurement of serum-ionised magnesium has recently become available, and we report the first study of the relation of this parameter to arrhythmias, left ventricular function and mortality in patients with an acute myocardial infarction. Serum-ionised magnesium was determined in 217 consecutive patients admitted to hospital with an enzyme confirmed AMI. 70 healthy subjects acted as a control group. The main study parameters were occurrence of arrhythmias, left ventricular function estimated by echocardiography, and mortality after 10 months for the AMI patients. AMI patients had significantly lower serum-ionised magnesium compared to healthy controls but the level of serum-ionised magnesium in the acute phase of a MI was neither related to arrhythmias, left ventricular function nor mortality.     

罗格列酮对兔急性心肌梗死后心室重构及心功能的影响

目的 探讨罗格列酮(Ros)对兔急性心肌梗死(AMI)后心室重构和心功能的影响.方法 将30只日本大耳白兔随机分为:假手术(Sham)组,AMI模型组,Ros组,每组10只.永久性结扎冠状动脉左前降支中上1/3处制作AMI模型,术后6h Ros组给予Ros 3mg/(kg·d)灌胃,AMI组及sham龃给予等量蒸馏水灌...     

Right ventricular infarction associated with anteroseptal myocardial infarction: a clinicopathologic study of nine cases.

The association of right ventricular (RV) infarction with inferoseptal myocardial infarction is well established. However, a question remains about the occurrence of RV infarction in association with anteroseptal myocardial infarction. To determine the frequency and clinical correlates of this entity, we studied autopsied hearts from patients with isolated anteroseptal left ventricular (LV) infarcts. Among 3,249 autopsy specimens, 88 cases were identified. From each, sections were taken from the RV anterior, lateral, and inferior regions at basal, middle, and apical levels. All 1,584 slides were reviewed by blinded assessment. RV and LV infarcts were compared to confirm similarity in age. Patient records and cardiac investigations were reviewed for evidence of RV involvement. Of the 88 hearts with anteroseptal LV infarcts, 9 (10%) had coexistent RV infarction (6, old; 3, new). For these 9, the RV infarction involved 11% to 33% of the RV area, and the left anterior descending coronary artery was the infarct-related artery in each. All 3 patients who had an echocardiographic examination within 4 weeks of anteroseptal LV infarction had RV dysfunction. One patient, studied 15 years after infarction, had a normal right ventricle by echocardiography. In 3 patients with acute myocardial infarction, right heart catheterization during the acute phase revealed increased right-sided diastolic pressures out of proportion to left-sided diastolic pressures (right atrial pressure to pulmonary capillary wedge pressure, 60% to 95%). In conclusion, 10% of patients with an isolated anteroseptal LV infarct had evidence of RV free wall infarction. The RV infarction was associated with identifiable hemodynamic and echocardiographic features.     

Plasma zinc and magnesium alterations in acute myocardial infarction

Summary In 31 patients suffering from acute myocardial infarction plasma zinc and magnesium concentrations were measured. In acute infarction plasma zinc concentrations were strikingly decreased and plasma magnesium concentrations slightly decreased. A close correlation between fall in zinc concentrations and the rise of serum CPK in these patients could be observed. No correlations were found between infarct localisation and sex and alterations in zinc concentrations. In contrast, a close correlation between fall in zinc content and severity of infarction occurred. Thus, the observed alterations in plasma zinc probably can be used as a diagnostic and prognostic indicator. Furthermore it should be considered whether zinc substitution would be of therapeutical benefit in patients suffering from acute myocardial infarction.Dedicated to Prof. Dr. med. H. Losse on the occasion of his 60th birthday     

Effect of a flexible ventricular restraint device on cardiac remodeling after acute myocardial infarction

The effects of a flexible ventricular restraint device on left ventricular (LV) dilatation and hypertrophy after transmural infarction are examined in an ovine model. Left ventricular remodeling and dilatation occurs after extensive myocardial infarction. A flexible ventricular restraint made from a nitinol mesh was evaluated in adult female sheep (n=14). Cardiac magnetic resonance imaging scans and hemodynamic measurements were completed before and 6 weeks after anterior myocardial infarction. Treatment animals (n=7) received passive ventricular restraint concurrently with LV infarction; the others (n=7) served as controls. Increases in LV end-diastolic volume index were significantly less in the restraint group than in controls (0.20+/-0.41 vs 0.83+/-0.50 ml/kg, p<0.03). End-systolic volumes increased less in treatment animals (0.43+/-0.28 vs 0.90+/-0.38 ml/kg, p<0.03). Control hearts showed an increase in LV mass after infraction, whereas LV mass decreased in restrained hearts (0.14+/-0.19 vs -0.25+/-0.36 g/kg, p<0.03). Hemodynamic studies showed similar changes after infarction for the control and the device group. Gross and microscopic examination showed no device-induced epicardial injury. A flexible ventricular restraint device attenuated remodeling after acute myocardial infarction in sheep.     

Hypokalemia and ventricular arrhythmias in acute myocardial infarction

In the present study, 408 patients with acute myocardial infarction were included. The serum concentration of potassium was assessed on admission. Episodes of ventricular fibrillation and/or ventricular tachycardia within the following 6 hours were registered. A significant positive correlation between hypokalemia and the incidence of malignant ventricular arrhythmias was demonstrated. Ongoing treatment with diuretics at the time of admission did not appear to be of any significance for the development of ventricular fibrillation or ventricular tachycardia. Out of 100 hypokalemic patients, only 33 were treated with diuretics. The main reason for hypokalemia in the early phase of an acute myocardial infarction is most likely an activation of the sympathetic nervous system leading to an influx of potassium from the extracellular to the intracellular body fluid compartment.     

卡托普利对兔急性心肌梗塞早期再灌注心室肌易损性的影响

目的：观察卡托普利对兔急性心肌梗塞（AMI）早期再灌注心室易损性的改变，探讨卡托普利对AMI早期再灌注心律失常的影响。方法：采用S1-S2程控电刺激方法同时测定开胸不阻断冠脉的无心肌缺血组（假手术对照组）、无心肌缺血用卡托普利灌流组（卡托普利组）、AMI早期缺血-再灌注对照组（再灌注对照组）和用卡托普利灌流早期缺血-再灌注组（再灌注卡托普利组）对家兔心室易损期（VVP）、室颤阈（VFT）、舒张阈（DT）、有效不应期（ERP）、T波顶点与VVP外缘处的时间关系（T_T-VVP）等电生理指标，卡托普利灌流速度0.1 mg·kg^-1·min^-1。结果：VVP、VFT、DT、ERP和T_T-VVP在假手术对照组和卡托普利组分别为(8.12±2.43) ms、(2.49±0.76) μJ、(3.62±0.59) V、(178.67±16.43) ms、(51.32±8.76) ms和(8.64±2.85) ms、(2.41±0.80) μJ、(3.85±0.58) V、(180.25±14.87) ms、(50.35±8.91) ms，组间比较皆无显著差异（P>0.05），再灌注对照组分别为(85.37±20.65) ms、(0.16±0.13) μJ、(2.25±0.48) V、(112.65±13.61) ms和(10.72±4.81) ms，再灌注卡托普利组分别为(56.34±15.21) ms、(0.26±0.14) μJ、(2.91±0.61) V、(137.83±15.24) ms和(14.84±7.89) ms；假手术对照组与再灌注对照组和再灌注卡托普利组比较有显著差异（P<0.01），再灌注对照组与再灌注卡托普利组比较亦有显著差异（P<0.01）。结论：卡托普利对无缺血心肌影响不明显；缺血-再灌注能明显增加急性心肌梗塞早期再灌注室性心动过速和/或心室颤动的发生，卡托普利对再灌注室性心动过速和/或心室颤动的发生有抑制作用。     

急性心肌梗塞早期心室易损性的电生理实验研究

本文采用Ｓ１－Ｓ２程控电刺激方法同时测定心室易期和室颤阈，并结合其它有关电生理指标，评价了急性心肌梗塞早期心室易损性。结果表明，急性心肌梗塞早期，心室易损期明显延长，室颤阈显著下降，起搏阈值降低，有效不应期缩短，强度间期曲线下移，心室易损期外缘向Ｔ波方向延伸，联律间期与折回间期呈负相关。根据上述指标分析了急性心肌梗塞早期室性心动过速和／或心室颤动产生的电生理机制以及心室易损期在ｒｏｎＴ室性早搏触发     

Effect of intravenous streptokinase as compared with that of tissue plasminogen activator on left ventricular function after first myocardial infarction

In a double-blind trial comparing two thrombolytic agents as treatment for acute myocardial infarction, we randomized 270 consecutive patients an average (+/- SD) of 2.5 +/- 0.6 hours after the onset of chest pain from a first myocardial infarction--135 to receive intravenous streptokinase (1.5 million units over 30 minutes) and 135 to receive intravenous recombinant tissue plasminogen activator (rt-PA) (100 mg over three hours). The primary end point was left ventricular function as assessed by cineangiography performed three weeks after infarction. The effects of the two agents on left ventricular function were similar. The ejection fraction was identical (58 +/- 12 percent) in both groups. The end-systolic volume was 61 +/- 29 ml in the streptokinase group and 66 +/- 31 ml in the rt-PA group (P not significant). Patency rates at three weeks for the infarct-related artery were also similar (75 percent in the streptokinase group and 76 percent in the rt-PA group). Reinfarction rates at 30 days were the same (5 percent) in both groups. One patient had a fatal intracerebral hemorrhage 13 hours after receiving rt-PA, and another had a fatal cerebellar hemorrhage 21 hours after receiving rt-PA for reinfarction nine days after treatment with streptokinase. An intention-to-treat analysis revealed that mortality at 30 days was 3.7 percent in the rt-PA group as compared with 7.4 percent in the streptokinase group (P greater than 0.2). Follow-up for a mean of 9.0 months revealed no significant difference in survival; we observed 12 deaths (8.9 percent) in the streptokinase group and 8 deaths (5.9 percent) in the rt-PA group (P = 0.34). We conclude that rt-PA and streptokinase, in the doses given, have similar effects on left ventricular function after a first myocardial infarction. Because of the small number of deaths, it is not possible to determine whether their effects on mortality are similar.     

Geographic variation in the incidence of myocardial calcification associated with acute myocardial infarction

There is reason to believe that calcium influx into heart muscle during acute myocardial infarction (AMI) can aggravate myocyte injury. Furthermore, the degree of such influx might correlate with the occurrence of microscopic myocyte calcification observed at autopsy. We have searched for evidence of myocyte calcification in hearts of patients found to have AMI at autopsy at the Veterans Administration Medical Center in Salt Lake City (SLCVA), a region with a low myocardial infection death rate, and at the George Washington University Medical Center in Washington, DC (GWUMC), a region with a high myocardial infection death rate. Of 23 consecutive cases examined under "blind" conditions at the GWUMC in which AMI was found, there were 15 instances of cardiac myocyte calcification observed in von Kossa-stained sections. Not a single example of myocyte calcification was found in 23 comparable cases at the SLCVA. The basis of this difference in myocyte calcification is unknown, but may be related to the fact that the Salt Lake City drinking water contains a higher level of magnesium, which is known to protect against soft tissue calcification, than does that of Washington, DC. This may be the basis for the apparent protection that dietary magnesium exerts against myocardial infarction death.     

Alterations of the myocardial skeletal framework in acute myocardial infarction with and without ventricular rupture. A preliminary report

Thinning and dilatation (expansion) of the infarct region and complete rupture of the ventricular wall are significant complications of acute transmural myocardial infarction associated with increased morbidity and mortality. The pathogenesis of these related events is unknown. Recent studies of myocardial connective tissue have delineated an extensive array of intercellular and pericellular structures which serve as a skeletal framework and which may modulate contractile activity. We have employed a modified silver impregnation method to visualize the connective tissue components by light microscopy. To explore whether the skeletal framework is altered in acute myocardial infarction with and without ventricular rupture, we studied 9 human hearts at autopsy, and 4 canine infarcts of known duration. The human infarctions included 4 nonruptured cases with infarcts 1-5 days old, and 5 ruptured cases with infarcts 3-10 days old. Sections from normal, lateral, and central infarct or ventricular rupture sites were stained with silver. The normal tissue from each heart served as a control. Silver staining was moderately decreased in the lateral infarct zones, and markedly decreased in the central non-ruptured infarct zones. In the 5 ventricular rupture cases, the rupture site had no silver staining. A similar pattern was observed in the 4 canine infarcts. Thus, we conclude that the skeletal framework is markedly altered in the central zone of acute myocardial infarction. The acute changes of silver stained connective tissue may contribute significantly to the development of infarct expansion or ventricular wall rupture.