Caffeine as a possible cause of ventricular arrhythmias during the healing phase of acute myocardial infarction

Caffeine (300 mg) was administered to each of 70 patients a mean (+/- standard error of the mean) of 7 +/- 1 days after the onset of acute myocardial infarction to determine its effects on ventricular arrhythmias. The study was designed as a randomized, double-blind, within-patient comparison between caffeine and placebo. Continuous Holter electrocardiographic recording for 4 hours showed no significant differences in the proportion of patients who had ventricular ectopic activity or the total number and complexity of ventricular premature complexes after caffeine vs placebo. Caffeine increased mean blood pressure from 116 +/- 2/70 +/- 1 mm Hg to a maximum of 125 +/- 3/78 +/- 2 mm Hg (p less than 0.001) at 4 hours. Plasma epinephrine increased (p less than 0.01) from 58 +/- 4 pg/ml to a maximum 88 +/- 6 pg/ml 3 hours after caffeine ingestion, whereas the plasma norepinephrine level did not change. Although caffeine caused significant hemodynamic and humoral responses in this population of relatively caffeine-naive postinfarction patients, it did not increase the occurrence or severity of ventricular arrhythmias.     

Hemodynamic effects of digoxin in acute myocardial infarction in man: a randomized controlled trial

Hemodynamic effects of digoxin in acute myocardial infarction (AMI) have been acknowledged to depend on the basal cardiocirculatory state. In the present study, the effects of digoxin in patients with AMI were evaluated in four hemodynamic subsets, based on the relationship between mean pulmonary capillary wedge pressure (PCWP, in mm Hg) and left ventricular stroke work index (LVSWI, in g-m/m2): subset 1: normal (less than or equal to 15 mm Hg) PCWP and normal (greater than or equal to 35 g-m/m2) LVSWI; subset 2: elevated (greater than 15 mm Hg) PCWP and normal LVSWI; subset 3: reduced (less than 35 g-m/m2) LVSWI and normal PCWP; and subset 4: elevated PCWP and LVSWI moderately reduced to a range between 16 and 34 g-m/m2. Forty patients were admitted to the study and were randomly assigned to one of two groups in each subset: control group (19 patients) and treated group (21 patients). Five patients were randomized into each of the subsets 2, 3, and 4 in both the control and treated groups, while in subset 1 there were four control and six digoxin-treated patients. Control patients were administered a placebo saline solution and digoxin-treated patients received 0.50 mg of the drug intravenously in 20 minutes. The effects of the placebo and of the drug were evaluated at 30, 60, and 90 minutes from the end of the infusion. Hemodynamic data did not vary in the control group, and digoxin did not exert any relevant effect in subsets 1 and 2. After drug infusion, cardiac index (Cl, in L/min/m2) significantly increased in subset 3 patients.(ABSTRACT TRUNCATED AT 250 WORDS)     

静脉注射重组人脑利钠肽对急性心肌梗死伴心力衰竭患者的急性血流动力学效应的研究

目的前瞻性对比静脉注射重组人脑利钠肽(rhBNP)与硝酸甘油(NIT)对急性心肌梗死伴心力衰竭(AMI-CDF)患者的急性血流动力学效应及安全性。方法连续住院的42例发病在12~24h的前壁AMI-CDF的患者,随机分为静脉滴注rhBNP组(给予冲击量1·5μg/kg弹丸式静脉注射,随后以0·0075μg·kg-1·min-1维持静脉滴注3h,调整剂量0·015~0·030μg·kg-1·min-1维持静脉注射21h,然后停药观察6h)和静脉滴注射NIT组(10~100μg/min静脉注射24h,然后停药观察6h),每组21例。比较两组治疗30h内的有创血流动力学参数、尿量、相应血清生化指标和治疗1周内的主要不良心脏事件(MACE)的发生情况。结果rhBNP组和NIT组间及治疗前后中心静脉压(CVP)和收缩压(SBP)无明显变化。rhBNP组治疗30min后心率较基础值显著下降[(95·3±7·4)比(118·0±8·2)次/min,P<0·05]并维持至停药后6h;NIT组治疗2h后心率才较基础值下降,差异有统计学意义[(92·8±6·8)比(109·2±7·6)次/min,P<0·05],而停药3~6h后心率又基本恢复到治疗前水平。rhBNP组治疗30min后肺小动脉契压(PCWP)较基础值下降48·9%[(13·6±6·4)比(26·9±7·5)mmHg(1mmHg=0·133kPa),P<0·05],治疗1h后心脏指数(CI)较基础值升高27·1%[(2·8±0·4)比(2·2±0·3)L·min-1·m-2,P<0·05];治疗后2h、3h、6h、12h、18h和24h的PCWP、CI仍均较治疗前有显著改善并可保持至停药后6h(P均<0·05)。NIT组治疗后2h的PCWP亦较治疗前有显著改善[(18·1±6·8)比(25·4±7·5)mmHg,P<0·05],但CI在治疗后3h才较治疗前显著改善,且停药6h后,以上两参数即恢复至治疗前水平。两组比较,rhBNP组治疗后30min至2h的PCWP的降低和CI的增加均较NIT组更为显著(P均<0·05);此后至治疗24h,两组以上参数渐趋一致;停药6h后rhBNP组的PCWP和CI仍显著优于NIT组(P均<0·05)。rhBNP组治疗30h内总尿量较NIT组有增多趋势,且rhBNP组血清钾浓度治疗后较治疗前明显升高[(3·4±0·5)比(4·0±0·4)mmol/L,P<0·05]。本研究未发现与rhBNP相关的症状性低血压及其他严重不良反应。两组治疗1周内的主要心血管事件的发生情况相似。结论对AMI-CDF的患者静脉注射rhBNP较之NIT有着更好的急性血流动力学效应和临床效果,且安全可行。     

Are rotating tourniquets useful for left ventricular preload reduction in patients with acute myocardial infarction and heart failure?

We examined the hemodynamic effects of congesting cuffs (rotating tourniquets) in 12 patients with first acute myocardial infarction and new onset of congestive heart failure 24 to 48 hours after admission. Congesting cuffs were applied for two periods of 15 minutes each, 15 minutes apart, and inflated to 30 mm Hg and 60 mm Hg consecutively. No change was noticed in mean pulmonary artery wedge pressure, which was 20 +/- 3 mm Hg at the beginning of the study and 19 +/- 3 mm Hg at the completion (P greater than .05, NS), nor in other hemodynamic and blood gases parameters. Patients' clinical conditions remained unchanged. We conclude that application of congesting cuffs at pressures of 30 mm Hg and 60 mm Hg does not result in any change in clinical or hemodynamic data in patients with acute myocardial infarction and new onset of congestive heart failure.     

Metoprolol treatment for two years after coronary bypass grafting: effects on exercise capacity and signs of myocardial ischaemia.

OBJECTIVE--To evaluate whether prophylactic treatment with metoprolol for two years after coronary artery bypass grafting improves working capacity and reduces the occurrence of myocardial ischaemia in patients with coronary artery disease. METHODS--After coronary artery bypass grafting, patients were randomised to treatment with metoprolol or placebo for two years. Two years after randomisation, a computerised 12-lead electrocardiogram was obtained during a standardised bicycle exercise test in 618 patients (64% of all those randomised). RESULTS--The median exercise capacity was 140 W in the metoprolol group (n = 307) and 130 W in the placebo group (n = 311) (P > 0.20). An ST depression of > or = 1 mm at maximum exercise was present in 34% of the patients in the metoprolol group and 38% in the placebo group (P > 0.20) and an ST depression of > or = 2 mm at maximum exercise was present in 11% in the metoprolol group and 16% in the placebo group (P = 0.09). The median values for maximum systolic blood pressure were 200 mm Hg in the metoprolol group and 210 mm Hg in the placebo group (P < 0.0001), while the median values for maximum heart rate were 126 beats/min in the metoprolol group and 143 beats/min in the placebo group (P < 0.0001). The occurrence of cardiac and neurological clinical events two years postoperatively among exercised patients was comparable in the treatment groups. CONCLUSIONS--Treatment with metoprolol for two years after coronary artery bypass grafting did not significantly change exercise capacity or electrocardiographic signs of myocardial ischaemia.     

Tolerance with low dose intravenous nitroglycerin therapy in acute myocardial infarction

The question of vascular tolerance was examined in 154 patients with acute myocardial infarction (64 anterior, 90 inferior) who were treated with prolonged low dose intravenous nitroglycerin in a recent randomized placebo-controlled study. The dose of nitroglycerin was carefully titrated to decrease mean blood pressure by 10% in normotensive patients and 30% in hypertensive (blood pressure greater than 140/90 mm Hg) patients, but not less than 80 mm Hg. Tolerance was defined as the need to increase the dose to maintain this hemodynamic effect. It was labelled "true" if chest pain was absent and "apparent" if chest pain was present. Group analysis of dose, pain scores, hemodynamic, 2-dimensional echocardiographic and clinical parameters monitored serially before and after therapy indicated benefit with nitroglycerin over placebo despite equalizing of blood pressures after 10 hours. Reversal of blood pressures and volumes after discontinuing nitroglycerin suggested lack of significant tolerance. However, detailed individual analysis suggested significant hemodynamic tolerance in 37 patients (24%), both in the true tolerance (12%) and apparent tolerance (12%) subgroups. Tolerance appeared early, requiring the dose to be increased by 30 +/- 39 micrograms/min within 11 +/- 9 hours. The dose was greater (p less than 0.001) in the tolerance than in the no tolerance subgroup, both before (60 vs 27 micrograms/min) and after (90 vs 38 micrograms/min) 10 hours. Tolerance blunted the beneficial effect on infarct size, but positive effects on function, topography and complications persisted.     

Metoprolol in acute myocardial infarction reduces ventricular arrhythmias both in the early stage and after the acute event

Fifty three of the 5778 patients included in the MIAMI (Metoprolol in Acute Myocardial Infarction) trial were investigated with long-term ECG recordings in order to evaluate the effect of acute beta-blockade on premature ventricular complexes in and after acute myocardial infarction. Twenty five patients were given placebo and 28 metoprolol in a double-blind randomized fashion for 15 days. After this period the patients were put on open beta-blockade without breaking individual study codes. The mean number of premature ventricular complexes during the inclusion day (day 0) was the same in the two groups. The median numbers were also similar in the two groups: 190 and 154 in the placebo and metoprolol groups, respectively. Metoprolol significantly reduced the median number of premature ventricular complexes in the randomized period. The median numbers on days 1, 2 and 15 were 146, 101, 84 in the placebo group and 73, 59 and 10 in the metoprolol group, respectively (P less than 0.05). Also during the further follow-up, when investigated 1, 3 and 6 months after the infarction, the median number of premature ventricular complexes was lower in the metoprolol group (74, 257, 142 in the placebo group and 7, 5 and 11 in the metoprolol group, P less than 0.05). This indicates that metoprolol treatment in the acute phase of myocardial infarction reduces ventricular arrhythmias both in the early stage and also after the acute event.     

Effect of early metoprolol injection followed by oral dosage on CK-MB release, and myocardial function in suspected acute myocardial infarction. A double-blind controlled study

The effect of metoprolol on indices of infarct size and left ventricular function was compared with that of placebo in a double-blind randomized trial in patients with definite or suspected acute myocardial infarction. Intravenous metoprolol (15 mg) or placebo was given within 24 h of the onset of symptoms, and oral treatment (200 mg daily) was continued for 15 days. Thirty-five patients received metoprolol and 34 patients placebo. The mean (+/- SD) of maximal creatinine phosphokinase (CK)-MB activities was 142 +/- 110 IU/l in the placebo group and 74 +/- 72 IU/l in the metoprolol group (p less than 0.001). The ECG QRS score at discharge from hospital was 5.22 +/- 4.47 and 4.61 +/- 3.06 (NS), respectively. Global left ventricular ejection fraction at rest was 44 +/- 14 and 51 +/- 15% (p = 0.054), respectively, and no change occurred in either group from rest to peak exercise. Ventricular fibrillation occurred in 1 placebo patient during the first day in hospital and in 1 metoprolol patient on the 14th day. Holter monitoring revealed no significant difference in the occurrence of ventricular arrhythmias during the first 24 h. Smaller enzyme release and higher ejection fraction suggest myocardial protection by early metoprolol treatment in acute myocardial infarction.     

Natural evolution of left ventricular haemodynamics following uncomplicated acute myocardial infarction

In an attempt to investigate the changes in left ventricular haemodynamics following uncomplicated myocardial infarction 95 patients with definite electrocardiographic signs of infarction, without clinical signs of cardiac failure, were monitored with a Swan Ganz catheter for the first 24 hours after admission to hospital. The median delay from onset of symptoms was 6.8 hours. Mean heart rate increased (83-86 beats/min; P less than 0.05) while stroke volume index fell (38.4-36.6 ml/m2; P less than 0.05); cardiac index therefore remained unchanged during the observation period. As a result of a fall in arterial pressure both systemic vascular resistance and left ventricular stroke work index fell significantly (P less than 0.01). Pulmonary wedge pressure also fell (13.6-10.5 mm Hg; P less than 0.001), but this fall was confined to patients whose initial reading was above the median of 13 mm Hg. Pulmonary wedge pressure fell both among the 41 patients who required some medical therapy (15.6-10.8 mm Hg; P less than 0.001) and the 54 who received no medication throughout the 24 hours (12.0-9.8 mm Hg; P less than 0.05). The 39 patients with anterior wall infarction had higher baseline pulmonary wedge pressure and systemic vascular resistance than the 42 with inferior wall infarction. Later the stroke volume and stroke work index were persistently lower reflecting the greater degree of impairment of left ventricular function in anterior wall infarction. In conclusion, following an uncomplicated myocardial infarction, cardiac index was maintained, despite a fall in stroke volume, by an increase in heart rate. Pulmonary wedge pressure showed both a spontaneous fall and a fall in those patients given additional medical therapy during the study period.     

Effects of beta-adrenoceptor blocking drugs on human sigmoid colonic motility

Effects of propranolol and metoprolol on sigmoid colonic motility were studied in 12 healthy volunteers in a double-blind randomized fashion. Colonic pressure was recorded 15-18 cm from anus and contractile activity quantified for periods of 25 min. On separate days propranolol, metoprolol, and placebo, respectively, was administered intravenously preceded by a control period. After propranolol, 10 mg intravenously, pressure activity increased significantly from 3.8 +/- 1.1 (SEM) kPa X min (28 +/- 8 mm Hg X min) to 5.9 +/- 1.0 kPa X min (44 +/- 8 mm Hg X min) (P less than 0.001). Also, after propranolol, 5 mg intravenously, the pressure activity was increased (P less than 0.05). After metoprolol, 10 mg intravenously, contractile activity increased from 4.3 +/- 0.9 kPa X min (32 +/- 7 mm Hg X min) to 6.1 +/- 1.0 kPa X min (46 +/- 8 mm Hg X min) (P less than 0.01). The two drugs caused equipotent reduction of heart rate. After placebo, no effect on sigmoid pressure or heart rate was observed. The study shows that unselective (propranolol) and beta 1-selective (metoprolol) beta-blocking drugs enhance distal colonic pressure in man. Colonic motility seems to be under sympathetic beta-adrenergic influence even under fairly unstrained conditions.     

Effect of metoprolol on indirect signs of the size and severity of acute myocardial infarction

In a double-blind randomized trial, 1,395 patients with suspected acute myocardial infarction (MI) were investigated to evaluate the possibility of limiting indirect signs of the size and severity of acute MI with the beta 1-selective adrenoceptor antagonist metoprolol. Metoprolol (15 mg) was given intravenously and followed by oral administration for 3 months (200 mg daily). Placebo was given in the same way. The size of the MI was estimated by heat-stable lactate dehydrogenase (LD[EC 1.1.1.27]) analyses and precordial electrocardiographic mapping. Lower maximal enzyme activities compared with placebo were seen in the metoprolol group (11.1 +/- 0.5 mukat X liter-1) when the patient was treated within 12 hours of the onset of pain (13.3 +/- 0.6 mukat X liter-1; n = 936; p = 0.009). When treatment was started later than 12 hours, no difference was found between the 2 groups. Enzyme analyses were performed in all but 20 patients (n = 1,375). Precordial mapping with 24 chest electrodes was performed in patients with anterior wall MI. The final total R-wave amplitude was higher and the final total Q-wave amplitude lower in the metoprolol group than in the placebo group. Patients treated with metoprolol less than or equal to 12 hours also showed a decreased need for furosemide, a shortened hospital stay, and a significantly reduced 1-year mortality compared with the placebo group, whereas no difference was observed among patients treated later on. After 3 months, however, there was a similar reduction in mortality among patients in whom therapy was started less than or equal to 12 hours and greater than 12 hours after the onset of pain. The results support the hypothesis that intravenous metoprolol followed by oral treatment early in the course of suspected myocardial infarction can limit infarct size and improve long-term prognosis.     

Effect of metoprolol on the submaximal stress test performed early after acute myocardial infarction

To determine the effect of beta-adrenergic blockade on the submaximal stress test after acute myocardial infarction (AMI), 36 post-AMI patients performed their treadmill test on 2 separate days, with and without metoprolol, in a double-blind, placebo-controlled, crossover design study. Rest and peak submaximal exercise heart rate was diminished by 100 mg of metoprolol administered twice daily (from 84 +/- 3 to 68 +/- 2 beats/min, p less than 0.001, and from 126 +/- 3 to 97 +/- 2 beats/min, p less than 0.001, respectively) compared with placebo. Rest and peak submaximal systolic blood pressure was also decreased (from 121 +/- 3 to 108 +/- 2 mm Hg, p less than 0.001, and from 151 +/- 4 to 124 +/- 3 mm Hg, p less than 0.001). Exercise-induced ST-segment depression of 1 mm or more from baseline occurred in 12 patients taking placebo. However, only 4 of these patients had ST depression when they exercised while taking metoprolol (p less than 0.05). Angina pectoris occurred in 4 patients taking placebo but in only 1 of these taking a beta-blocking drug. It is concluded that beta-blocking therapy renders the post-AMI submaximal stress test less sensitive for markers of exercise-induced ischemia than if the test is performed without the drug. Therefore, when using the prognostic information of published studies, it is important to define the conditions surrounding the exercise test.     

Hemodynamic effects of intermittent transdermal nitroglycerin in chronic congestive heart failure

The hemodynamic effects of intermittent and continuous treatment with transdermal nitroglycerin, 10 mg/24 hours, were compared in 10 patients with chronic congestive heart failure (CHF). Eight patients responded to initial application with more than a 20% reduction in mean pulmonary artery wedge pressure. Cardiac index increased from a control value of 2.1 +/- 0.5 to 2.4 +/- 0.6 liters/min/m2 at 2 hours (p less than 0.05) and mean pulmonary wedge pressure was reduced from 22 +/- 5 to 16 +/- 6 mm Hg (p less than 0.01). The 2 nonresponders had the largest left ventricular volumes on 2-dimensional echocardiograms. Responders were randomized to intermittent (16 hours/day) or continuous (24 hours/day) treatment for 1 month followed by a month of the alternate treatment. After 1 month of intermittent treatment, the hemodynamic response after reapplication was similar to the initial response. After another month of continuous treatment, hemodynamic values 24 hours after application were similar to initial control values and there was no change after removal and reapplication. Thus, the moderate vasodilator effect of transdermal nitroglycerin in CHF is maintained with intermittent treatment, whereas tolerance develops with continuous treatment.     

Intravenous nitroglycerin for rest angina. Potential pathophysiologic mechanisms of action

Twenty patients with refractory rest angina pectoris were treated with intravenously (IV) administered nitroglycerin (mean dosage, 72.4 micrograms/min; range, 15 to 226 micrograms/min). There was a considerable reduction or abolition in the number of ischemic episodes in 85% of patients without overall substantial changes in heart rate, mean arterial BP, pulmonary capillary wedge pressure (PCWP), and pulmonary arterial mean pressure. However, those patients with an initial PCWP of more than 12 mm Hg or a systolic pressure of more than 130 mm Hg had a substantial reduction in PCWP and systolic BP following IV nitroglycerin. We conclude that IV nitroglycerin may relieve rest angina by different pathophysiologic mechanisms. In some patients, IV nitroglycerin favorably altered the hemodynamic determinants of myocardial oxygen consumption. In others, however, no change in these determinants occurred, suggesting a direct effect on the coronary circulation.     

Effect of beta-blockade on low heart rate-related ischemia during mental stress.

To explore the effect of beta-adrenergic blockade on low heart rate-related (mental stress) ischemia, 19 patients with coronary artery disease were randomized into a double-blind crossover trial of metoprolol, 100 mg twice daily, and underwent serial mental stress/bicycle exercise studies. Mental stress-induced wall motion abnormalities occurred at a lower heart rate than exercise-induced wall motion abnormalities during placebo administration (81 +/- 16 vs. 123 +/- 20 beats/min, p less than 0.05). Metoprolol reduced the mean magnitude of exercise-induced wall motion abnormalities (2.8 +/- 2.0 vs. 1.6 +/- 2.4, p = 0.003); improvement was related to the magnitude of hemodynamic beta-blockade effect. Metoprolol did not significantly reduce the mean magnitude of mental stress-induced wall motion abnormalities (3.0 +/- 2.2 vs. 2.6 +/- 2.2), although individual responses predominantly either improved (50%) or worsened (29%). Unlike exercise, the magnitude of hemodynamic beta-blockade did not predict mental stress response and metoprolol did not block mental stress-induced blood pressure elevations. Patients with abolition of exercise-induced ischemia were more likely to have reduction of mental stress-induced ischemia. Patients whose ischemia worsened with metoprolol during mental stress had more easily inducible ischemia, as assessed by exercise-induced placebo wall motion abnormality, chest pain and prior myocardial infarction. Beta-blockade was associated with a lowering of ischemia-related hemodynamic thresholds compared with placebo. These results suggest that beta-blockade has a variable effect on low heart rate-related ischemia that may be due to a lack of effect on mental stress-induced blood pressure elevation in patients with easily induced ischemia or to effects on coronary vasomotor tone, or both.     

Effect of vasopressin on hemodynamics in patients with refractory cardiogenic shock complicating acute myocardial infarction

In a retrospective study of 36 patients who developed cardiogenic shock after myocardial infarction, intravenous vasopressin therapy increased mean arterial pressure from 56 to 73 mm Hg at 1 hour (p < 0.001) and maintained it for 24 hours without changing pulmonary capillary wedge pressure, cardiac index, urine output, or other inotropic requirements. After norepinephrine administration, mean pulmonary capillary wedge pressure increased at 1 hour from 21 to 24 mm Hg (p = 0.04); however, this increase was not sustained at 12 and 24 hours. Norepinephrine was associated with a significant increase in cardiac power index at 24 hours, whereas there was only a trend for an increase in cardiac power with vasopressin therapy. In a cohort of patients who developed refractory cardiogenic shock after myocardial infarction, vasopressin was associated with increased mean arterial pressure and no adverse effect on other hemodynamic parameters.     

Orally administered isosorbide dinitrate in patients with and without left ventricular failure due to acute myocardial infarction.

The oral effectiveness of 10 mg followed by 20 mg of isosorbide dinitrate in 21 patients with acute mycardial infarction was studied over a period of 13 hours. The patients were grouped according to initial left ventricular filling pressure: group I, pressure less than 20 mm Hg, and group II, pressure more than 20 mm Hg. Patients in group II had left ventricular failure. In both groups isosorbide dinitrate resulted in a significant decrease in pulmonary arterial pressure. The left ventricular filling pressure decreased in group I from 13.6 +/- 4.0 to 7.1 +/- 2.6 mm Hg (mean +/- 1 standard deviation) and in group II from 26.9 +/- 4.6 to 19.0 +/- 3.6 mm Hg (P less than 0.001). Cardiac output decreased in group I from 5.1 +/- 1.0 to 4.5 +/- 0.9 liters/min, whereas in group II it increased significantly from 3.5 +/- 0.8 to 4.1 to 0.9 liters/min (P less than 0.001). In both groups, peripheral arterial blood pressure decreased (P less than 0.60). Heart rate remained constant. Whether cardiac output increased or decreased was found to be dependent on the initial left ventricular filling pressure. In patients with an initially high value (above 20 mm Hg), the increase in cardiac output is probably due to the reduction of afterload. An additional factor may be the decrease in left ventricular filling pressure, which leads to an improved blood supply in the affected mural segments as a result of the decrease in the extravascular component of the coronary resistance. Significant changes in cardiac output and left ventricular filling pressure were achieved 3 to 5 hours after oral administration of isosorbide dinitrate. Clinical signs of failure were less pronounced. Isosorbide dinitrate is, therefore, a therapeutic agent in the treatment of left ventricular failure due to acute myocardial infarction.     

Effect of intravenous metoprolol on left ventricular performance in Q-wave acute myocardial infarction

To determine the effects of intravenous metoprolol on left ventricular (LV) function in acute myocardial infarction (AMI), 16 patients were studied within 48 hours of Q-wave AMI (mean ejection fraction 47 +/- 6%, mean pulmonary artery wedge pressure 22 +/- 6 mm Hg) with high fidelity pressure and biplane cineventriculography before and after intravenous metoprolol (dose 12 +/- 4 mg). Heart rate decreased from 90 +/- 13 to 74 +/- 11 beats/min (p less than 0.001), pulmonary arterial wedge pressure and LV end-diastolic pressure were unchanged (22 +/- 6 to 21 +/- 6 and 27 +/- 8 to 26 +/- 8 mm Hg, respectively), despite impaired LV relaxation (P = Poe-t/T) after intravenous metoprolol (T from 59 +/- 13 to 72 +/- 12 ms, p less than 0.001). Peak systolic circumferential LV wall stress decreased after beta-adrenergic blockade (330 +/- 93 to 268 +/- 89 g/cm2, p less than 0.05) and LV contractility decreased (dP/dtmax from 1,480 +/- 450 to 1,061 +/- 340 mm Hg/s, p less than 0.001). The ejection fraction decreased (48 +/- 7 to 43 +/- 7%, p less than 0.05) due to an increase in LV end-systolic volume (85 +/- 19 to 93 +/- 19 ml, p less than 0.05) since LV end-diastolic volume was unchanged (161 +/- 30 to 163 +/- 30 ml, difference not significant). In patients with Q-wave AMI, intravenous metoprolol reduces the major determinants of myocardial oxygen demand including heart rate, contractility and peak systolic wall stress. Further, despite decreased heart rate, (+)dP/dtmax, ejection fraction, isovolumic relaxation, LV end-diastolic pressure and end-diastolic volume remain unchanged.     

Impaired response of atrial natriuretic factor to blood volume expansion in acute right ventricular infarction.

To assess the role of atrial natriuretic factor (ANF) in right ventricular (RV) infarction, 30 patients with inferior wall acute myocardial infarction (15 with RV involvement) and normal left heart filling pressures were studied 39 +/- 12 hours after the onset of symptoms. Serial measurements of cardiac output, right atrial, pulmonary artery and pulmonary wedge pressures, as well as plasma ANF, plasma renin activity, plasma aldosterone and vasopressin were obtained before and 30 minutes after acute volume expansion to raise wedge pressure greater than or equal to 20 mm Hg. Baseline mean right atrial pressure and plasma ANF levels were greater in patients with than without RV infarction (8 +/- 3 vs 5 +/- 2 mm Hg; p less than 0.0001, and 4.6 +/- 2.9 vs 2.7 +/- 1.5 fmol/ml; p less than 0.05, respectively). There were no differences in other baseline hemodynamic or humoral parameters between both groups. After volume expansion, pulmonary wedge pressure was similar in both groups, but right atrial pressure increased to higher levels in patients with RV infarction (19 +/- 2 vs 14 +/- 2 mm Hg; p less than 0.0001). Despite this greater stimulus for ANF secretion, the increase in plasma ANF was less pronounced in patients with RV infarction (63 +/- 81 vs 455 +/- 417%; p less than 0.002), especially among those with paroxysmal supraventricular tachyarrhythmias. Thus, despite higher baseline plasma levels of ANF, response to volume loading is markedly attenuated in patients with RV infarction complicating an inferior wall acute myocardial infarction.     

Comparison of perindopril versus captopril for treatment of acute myocardial infarction.

Angiotensin-converting enzyme (ACE) inhibitors reduce mortality in patients with acute myocardial infarction (AMI), but these benefits might be limited by acute hemodynamic changes and difficulties in titrating to recommended doses. The objective of this study was to compare the hemodynamic changes and tolerability of perindopril with captopril after AMI. We randomized 212 patients to receive either captopril (n = 102) or perindopril (n = 110) within 72 hours of AMI. Captopril was given as an initial dose of 6.25 mg, and then 50 mg/day on day 1 and 100 mg/day thereafter. The corresponding doses of perindopril were 2, 4, and 8 mg/day. Acute hemodynamic changes, the percentage of patients who reached target doses, and in-hospital and 6-month cardiovascular events were monitored. Baseline clinical characteristics of the 2 groups were identical, but patients randomized to perindopril were in a higher Killip class (1.4 +/- 0.6 vs 1.2 +/- 0.5, p = 0.05). During the first 6 hours, treatment with perindopril resulted in higher minimal systolic (97 +/- 15 vs 91 +/- 14 mm Hg, p <0.01) and diastolic blood pressure (BP) (57 +/- 11 vs 54 +/- 10 mm Hg, p <0.02), later occurrence of minimal BP (3.6 +/- 0.2 vs 2.7 +/- 0.1 hour, p <0.001), and a lower incidence of persistent hypotension with systolic BP < 90 mm Hg for > or =1 hour (5% vs 16%; p < 0.01) compared with captopril. At initial administration, target doses of perindopril and captopril were attained in 97% and 82% of the patients, respectively (p < 0.01). After 6 months, there were no differences between patients treated with perindopril and captopril in mortality rates (6% vs 13%, p = 0.16) and need for revascularization (20% vs 21%, p = 0.9). Thus, in patients during AMI, perindopril treatment showed better short-term tolerance than treatment with captopril, with significantly less acute hemodynamic changes and fewer withdrawals.