The effect of bretylium tosylate on ventricular arrhythmias in patients with acute myocardial infarction]

Sixty three patients with the acute myocardial infarction, aged between 34 and 85 years, admitted to the Intensive Cardiological Care Unit during the first 12 hours following the infarction were randomly divided into two groups. Patients of group I (20 subjects) were treated with nitroglycerin and additional intravenous infusions of bretylium tosylate in the dose of 5 mg/kg administered every 6 hours for 48-72 hours. Patients of group II (33 subjects) were mainly treated with intravenous nitroglycerin. A type and incidence of the ventricular arrhythmias, conduction disorders in AV node, and hemodynamic complications were analysed during the first 72 hours. It was found that bretylium tosylate reduces the incidence of ventricular arrhythmias accompanying myocardial infarction but after 2-3 hours following its administration (p < 0.05). Therefore, bretylium tosylate should be administrated to patients with the acute myocardial infarction in combination with other rapidly acting anti-arrhythmic drug. Bretylium tosylate increases also the effectiveness of electric defibrillation in patients with ventricular fibrillation or ventricular tachyarrhythmia. No evidence of the effectiveness of bretylium tosylate on atrio-ventricular conduction and hemodynamic complications of myocardial infarction was found.     

Late ventricular potentials--a new risk factor for cardiac arrhythmias in recent myocardial infarction

The study involved 150 patients with recent myocardial infarction. Ventricular lat potentials were registered in these patients during the first 48 hours and repeated in the third week. Ventricular late potentials were found in 31 patients (21%) in the first 48 hours, and in 27 out of 134 patients (20%) before the release from the hospital. Comparing potentials registration in the acute and late phase of the myocardial infarction it was found that ventricular late potentials occurred in 6 and disappeared in 4 patients. Stable ventricular tachycardia was significantly more frequent (p less than 0.001) within the first 48 hours in patients with ventricular late potentials than those without them (19% vs 3%). Ventricular late tachycardia (over 48 hours) was more frequent (p less than less than 0.001) in patients with ventricular late potentials (21% vs 1%). Premature ventricular excitations of Lown class 2-5 were also more frequent (p less than 0.001) in the group of patients with ventricular late potentials than those without these potential (81% vs 24%) when registered with a 24-hour Holter ECG in the third week following myocardial infarction. Antiarrhythmic drugs did not produce the regression of ventricular late potentials. Non-invasive registration of ventricular late potentials helps to select patients with life-threatening ventricular arrhythmias following the acute myocardial infarction.     

Role of exercise testing early after myocardial infarction in identifying candidates for coronary surgery.

It has been suggested that ST depression in lead V5 or equivalent on early exercise testing after acute myocardial infarction predicts a high risk of death. To evaluate exercise testing and radionuclide ventriculography in this context 103 consecutive patients with myocardial infarction who were able to undertake a limited exercise test before discharge from hospital were exercised and underwent gated blood pool scanning. No serious complications resulted from exercise testing. Twenty nine patients developed ST depression in lead V5, 19 had exertional hypotension, 31 developed a heart rate of greater than or equal to 130 beats/min, and 15 had complex ventricular arrhythmias. Death during the first year after discharge from hospital was associated with exertional hypotension (p less than 0.001) and a heart rate on exercise testing of greater than or equal to 130 beats/min (p less than 0.05); these two variables identified all nine deaths. Inability to complete the exercise protocol for any reason was also predictive of death (p less than 0.01). Ventricular arrhythmias and ST depression in lead V5 induced by exercise were not significantly associated with an increased risk of death. The mean (SD) radionuclide ejection fraction in the patients who died was 29 (16%) compared with 43 (11)% in the patients who survived (p less than 0.001). ST changes on exercise testing after myocardial infarction appear to be less predictive of later complications than haemodynamic signs, which may indicate left ventricular damage rather than ischaemia.     

Electrocardiographic evidence for cocaine cardiotoxicity in cat

Recent case studies suggest that cocaine overdose may produce life-threatening cardiac arrhythmias. We therefore investigated its effects on the electrocardiogram (leads II and V1) and arterial blood pressure in cats anesthetized with pentobarbital. Cocaine was administered by intravenous infusion over a 2-min interval at 1 mg/kg in 10 cats. In 5 out of 10 cats an additional infusion of 3 mg/kg cocaine was also administered after hemodynamic and electrocardiographic parameters had returned to control values (i.e., within 10 min). During and following infusion of 1 mg/kg cocaine, no significant change in heart rate or systolic or diastolic blood pressure were found, however the QRS duration increased by 38% (from 46 +/- 5 to 64 +/- 12 ms) (p less than 0.01). Evidence for bundle branch block and (or) premature ventricular beats was observed in 9 out of 10 cats after 1 mg/kg cocaine. Infusion of a further 3 mg/kg cocaine in five cats significantly lowered diastolic blood pressure (from 98 +/- 18 to 64 +/- 28 mmHg; 1 mmHg = 133.3 Pa) (p less than 0.01), and further prolonged QRS to 79 +/- 14 ms, a 75% increase from the mean control value (p less than 0.01). In addition, 1st and 2nd degree atrioventricular block, ventricular extrasystoles, and ectopic rhythms (AV junctional or idioventricular) were observed in four out of five cats given 3 mg/kg cocaine. Mean plasma concentrations of cocaine were 1.37 +/- 0.39 micrograms/mL (4.28 +/- 1.22 microM) (n = 5) at the end of a 1 mg/kg infusion and 2.93 +/- 0.43 micrograms/mL (9.16 +/- 1.34 microM) after a 3 mg/kg infusion (n = 3).(ABSTRACT TRUNCATED AT 250 WORDS)     

Lignocaine Therapy after Acute Myocardial Infarction

Thirty-five patients with ventricular dysrhythmias and seven with other dysrhythmias after acute myocardial infarction were treated with intravenous lignocaine.Satisfactory initial suppression of ventricular ectopic beats was achieved in 27 (82%) of 33 patients after either a 50-mg. bolus or a 50-mg. bolus followed by a 100-mg. bolus of intravenous 2% lignocaine. Continuous suppression of ventricular ectopic beats was accomplished in 21 (78%) of these 27 patients by continuous intravenous lignocaine infusions of 1 to 2 mg. per minute. Recurrence of ventricular ectopic beats occurred in four patients despite lignocaine infusion rates of up to 6 mg. per minute. Six patients with ventricular ectopic beats developed ventricular fibrillation despite satisfactory initial suppression of their dysrhythmia by lignocaine. In three of them ventricular fibrillation supervened while they were receiving a lignocaine infusion and two subsequently died. Unheralded ventricular fibrillation occurred in three other patients between four and seven days after completing the full course of lignocaine therapy.Toxic effects of lignocaine were minimal in patients receiving 1 to 2 mg. per minute.     

Intravenous tissue plasminogen activator and size of infarct,left ventricular function,and survival in acute myocardial infarction.

STUDY OBJECTIVE--To assess effect of intravenous recombinant tissue type plasminogen activator on size of infarct, left ventricular function, and survival in acute myocardial infarction. DESIGN--Double blind, randomised, placebo controlled prospective trial of patients with acute myocardial infarction within five hours after onset of symptoms. SETTING--Twenty six referral centres participating in European cooperative study for recombinant tissue type plasminogen activator. PATIENTS--Treatment group of 355 patients with acute myocardial infarction allocated to receive intravenous recombinant plasminogen activator. Controls comprised 366 similar patients allocated to receive placebo. INTERVENTION--All patients were given aspirin 250 mg and bolus injection of 5000 IU heparin immediately before start of trial. Patients in treatment group were given 100 mg recombinant tissue plasminogen activator over three hours (10 mg intravenous bolus, 50 mg during one hour, and 40 mg during next two hours) by infusion. Controls were given placebo by same method. Full anticoagulation treatment and aspirin were given to both groups until angiography (10-22 days after admission). beta Blockers were given at discharge. END POINT--Left ventricular function at 10-22 days, enzymatic infarct size, clinical course, and survival to three month follow up. MEASUREMENTS AND MAIN RESULTS--Mortality was reduced by 51% (95% confidence interval -76 to 1) in treated patients at 14 days after start of treatment and by 36% (-63 to 13) at three months. For treatment within three hours after myocardial infarction mortality was reduced by 82% (-95 to -31) at 14 days and by 59% (-83 to -2) at three months. During 14 days in hospital incidence of cardiac complications was lower in treated patients than controls (cardiogenic shock, 2.5% v 6.0%; ventricular fibrillation, 3.4% v 6.3%; and pericarditis, 6.2% v 11.0% respectively), but that of angioplasty or artery bypass, or both was higher (15.8% v 9.6%) during the first three months. Bleeding complications were commoner in treated than untreated patients. Most were minor, but 1.4% of treated patients had intracranial haemorrhage within three days after start of infusion. Enzymatic size of infarct, determined by alpha hydroxybutyrate dehydrogenase concentrations, was less (20%, 2p = 0.0018) in treated patients than in controls. Left ventricular ejection fraction was 2.2% higher (0.3 to 4.0) and end diastolic and end systolic volumes smaller by 6.0 ml (-0.2 to -11.9) and 5.8 ml (-0.9 to -10.6), respectively, in treated patients. CONCLUSION--Recombinant tissue type plasminogen activator with heparin and aspirin reduces size of infarct, preserves left ventricular function, and reduces complications and death from cardiac causes but at increased risk of bleeding complications4+     

Clinical Experience with Dextro-Alprenolol

Experience with dextro-alprenolol in nine patients has shown that it is relatively ineffective in treating arrhythmias associated with acute myocardial infarction. Marginal effectiveness in the control of ventricular ectopic beats after myocardial infarction is outweighed by an appreciable hypotensive effect with risk of infarction. The drug was ineffective in the management of supraventricular arrhythmias.     

Effect of intravenous infusion of insulin in diabetics with acute myocardial infarction.

Diabetes mellitus is associated with a high mortality after myocardial infarction. To see whether this may be decreased by improved diabetic control the effect of an insulin infusion regimen was studied in patients with acute myocardial infarction. From April 1982 to April 1983, 33 diabetics were admitted with acute myocardial infarction. Those being treated with diet alone or oral hypoglycaemic drugs continued with this unless control was poor, when they were changed to a "sliding scale" regimen of subcutaneous insulin injections thrice daily. Those already receiving insulin were maintained on thrice daily subcutaneous injections. From April 1983 to April 1984, 29 diabetics had acute myocardial infarction. Those receiving treatment with oral hypoglycaemic drugs or insulin were changed to continuous intravenous infusion of insulin, the aim being to maintain the blood glucose concentration at 4-7 mmol/I (72-126 mg/100 ml). Those being treated with diet alone continued with this if blood glucose concentrations were acceptable. Total mortality fell from 42% in the first year to 17% in the second (p less than 0.05). Over the same period mortality among non-diabetic patients with myocardial infarction did not change significantly. There was a significant fall in cardiac arrhythmias (expressed as the percentage of patients in whom arrhythmias were recorded) from 42% to 17% (p less than 0.05). The most significant fall in the incidence of complications occurred in those who had been receiving oral hypoglycaemic drugs on entry to the study (87% to 50%, p less than 0.05).     

Circadian Variations of Heart Rate and Premature Beats in Healthy Subjects and in Patients with Previous Myocardial Infarction

Chronobiological analysis of the circadian variations of heart rate, ventricular and atrial ectopies, was carried out on 11 patients with previous myocardial infarction matched with 11 controls. Individual circadian rhythms in heart rate were seen in all the control subjects but only in 6 patients with previous myocardial infarction. The behaviour of the individual circadian rhythms of premature beats was not significantly different between the two groups. A significant group rhythm in ectopies was not demonstrated, nevertheless a trend to higher frequency of arrhythmias during the activity span was detected. These results do not allow to postulate a circadian pattern of arrhythmias common to all the subjects examined. Therefore, the individual circadian behaviour of premature atrial and ventricular beats should be recognized for monitoring antiarrhythmic therapy. A significant group rhythm in heart rate was demonstrated for the two populations studied and linear discriminant analysis showed that the amplitude of this rhythm was significantly lower in patients than in controls. Possibly, myocardial infarction may affect the sinus node function producing a “flattened” range of heart rates during the 24 hours.     

Effects of intravenous magnesium in suspected acute myocardial infarction: overview of randomised trials.

OBJECTIVE--To investigate the effect of intravenous magnesium on mortality in suspected acute myocardial infarction. DESIGN--Systematic overview of all available randomised trials in which patients were allocated to receive either intravenous magnesium or otherwise similar treatment without magnesium. SETTING--Coronary care units of several hospitals. PATIENTS--1301 patients in seven randomised trials. MAIN OUTCOME MEASURE--Short term mortality. RESULTS--Considering the seven trials collectively there were 25 (3.8%) deaths among 657 patients allocated to receive magnesium and 53 (8.2%) deaths among 644 patients allocated control, generally during hospital follow up. This represents a 55% reduction in the odds of death (p less than 0.001) with 95% confidence intervals ranging from about one third to about two thirds. 70 of 648 patients allocated magnesium compared with 109 of 641 controls had serious ventricular arrhythmias, suggesting that magnesium reduces the incidence, though the definition varied among trials. Other adverse effects were rare in the limited number of patients for whom this data were available. CONCLUSION--Despite the limited number of patients randomised this overview suggests that intravenous magnesium therapy may reduce mortality in patients with acute myocardial infarction. Further large scale trials to confirm (or refute) these findings are desirable.     

Effect of desflurane-induced preconditioning following ischemia-reperfusion on nitric oxide release in rabbits

Nitric oxide (NO) is the mediator of ischemic preconditioning against myocardial infarction. Desflurane produces anesthetic preconditioning to protect the myocardium against infarction. In the model of myocardial ischemia-reperfusion injury in rabbits, we evaluated desflurane-induced ischemic preconditioning and studied its mechanism of NO synthesis. Thirty-two male adult New Zealand white rabbits were anesthetized with intravenous (IV) 30 mg/kg pentobarbital followed by 5 mg/kg/hr infusion. All rabbits were subjected to 30 minutes (min) long lasting left anterior descending coronary artery (LAD) occlusion and three hours (hr) of subsequent reperfusion. Before LAD occlusion, the rabbits were randomly allocated into four groups for preconditioning treatment (eight for each group). The control group did not receive any preconditioning treatment. The desflurane group received inhaled desflurane 1.0 MAC (minimal end-tidal alveolar concentration) for 30 min that was followed by a 15 min washout period. The L-NAME-desflurane group received L-NAME (NG-nitro-L-arginine methyl ester; non-selective Nitric Oxide Synthetase (NOS) inhibitor) 1 mg/kg IV 15 min before 1.0 MAC inhaled desflurane for 30 min. The L-NAME group received L-NAME 1 mg/kg IV. Infarct volume, ventricular arrhythmia, plasma lactate dehydrogenase (LDH), creatine kinase (CK) activity and myocardial perfusion were recorded simultaneously. We have found that hemodynamic values of the coronary blood flow before, during, and after LAD occlusion were not significantly different among these four groups. For the myocardial ischemia-reperfusion injury animals, the infarction size (mean +/- SEM) in the desflurane group was significantly reduced to 18 +/- 3% in the area at risk as compared with 42 +/- 7% in the control group, 35 +/- 6 in the L-NAME group, and 34 +/- 4% in the L-NAME-desflurane group. The plasma LDH, CK levels, and duration of ventricular arrhythmia were also significantly decreased in the desflurane group during ischemia-reperfusion injury. Our results indicate that desflurane is an anesthetic preconditioning agent, which could protect the myocardium against the ischemia-reperfusion injury. This beneficial effect of desflurane on the ischemic preconditioning is probably through NO release since L-NAME abrogates the desflurane preconditioning effect.     

参麦注射液联合阿替普酶治疗急性心肌梗死的临床效果研究

目的:研究参麦注射液联合阿替普酶治疗急性心肌梗死的临床效果。方法:选择2015年1月～2016年12月在我院进行诊治的急性心肌梗死患者98例,随机分为两组,每组各49例。对照组静脉滴注阿替普酶100 mg治疗,于90 min内滴注完毕,先静脉推注15 mg,再于30 min内静脉滴注50 mg阿替普酶,最后于60 min内静脉滴注35 mg,每天1次;观察组联合静脉滴注参麦注射液治疗,每次100 mL,每天1次。比较两组的临床治疗效果,治疗前后左心室射血分数、左心室舒张末期内径、左心室后壁厚度等心功能指标及血清心肌肌钙蛋白I(c TnI)、肌酸激酶同工酶(CK-MB)、超氧化物歧化酶以及(SOD)内皮素1(ET-1)水平的变化。随访半年,观察两组的预后情况(再梗死、梗死后心绞痛、血管再通以及冠脉血栓的发生率)。结果:治疗后,观察组的有效率为91.83%(45/49),明显高于对照组[71.43%(35/49)](P0.05);两组的左心室射血分数、左心室舒张末期内径、左心室后壁厚度均较治疗前明显改善(P0.05),且观察组的改善程度明显优于对照组(P0.05);两组的血清TnI、CK-MB、ET-1水平均较治疗前明显降低(P0.05),血清SOD水平均较治疗前明显升高(P0.05),且观察组以上指标的改善情况较对照组更为明显(P0.05);观察组再梗死、梗死后心绞痛以及冠脉血栓的发生率均明显低于对照组(P0.05),血管再通的发生明显高于对照组(P0.05)。结论:与单独使用阿替普酶对比,参麦注射液联合阿替普酶治疗急性心肌梗死临床疗效和安全性较好。     

Specific and gender differences between hospitalized and out of hospital mortality due to myocardial infarction

In this paper, the authors evaluate gender related differences of myocardial infarction mortality before and after hospital admittance. Myocardial infarction mortality in the Clinical Hospital Split in the seven years period between 2000 and 2006, have been analyzed together with out of hospital sudden death patients with acute myocardial infarction established during autopsy. During the seven year period between 2000 and 2006, 3434 patients were treated for myocardial infarction in the Split Clinical Hospital, 2336 (68%) males and 1098 (32%) females with a 12% total mortality (427 patients). The annual number of hospitalized persons has been increasing during that period (474 in yr. 2000 us. 547 in yr. 2006), while mortality decreased from 15% in 2000 to 9.6% in 2006. Female patients had significantly higher hospital mortality than male patients, (228 or 21% vs. 202 or 9%, p<0.05). Women also had significantly higher total AMI mortality (23.7% vs. 15,7%, p <0.05). Anterior myocardial infarction with ST elevation in precordial leads had significantly higher mortality (19%) compared to patients with lateral (11%), inferior (10%) myocardial infarction with ST elevation and also NSTEMI (4%) mortality p<0.05. Female patients more frequently die in hospital, 84% (230) than out of hospital 16% (43). From the total number of AMI deaths (388) in male patients, 56% (217) were in hospital and 44% (171) out of hospital (p<0.001). Men had significantly higher prehospital mortality rate than women (81% vs. 19%, p<0.05). Men also more frequently died from ventricular fibrillation (22% vs. 10%, p<0.05), while women died more frequently of heart failure, cardiogenic shock, and myocardial rupture (33% vs. 15% p<0.05). Regarding the total number of deaths from myocardial infarction men had significantly higher prehospital mortality compared to women (178 or 7.3% vs. 43 or 3.7%, p<0.05). Anterior myocardial infarction had a significantly higher rate in patients dying pre-hospital (58%), in contrast to inferior (36%) and lateral myocardial infarction with ST elevation (6%) p<0.05. We have concluded that male patients die more frequently within the first few hours of AMI mostly due to malignant arrhythmias, while female patients died in sub acute stage due to heart failure while being hospitalized. Nevertheless total mortality of AMI remains significantly higher in women.     

Inhibition of ischemia/reperfusion-induced damage by dexamethasone in isolated working rat hearts: the role of cytochrome c release

We investigated the contribution of dexamethasone treatment on the recovery of postischemic cardiac function and the development of reperfusion-induced arrhythmias in ischemic/reperfused isolated rat hearts. Rats were treated with 2 mg/kg of intraperitoneal injection of dexamethasone, and 24 hours later, hearts were isolated according to the 'working' mode, perfused, and subjected to 30 min global ischemia followed by 120 min reperfusion. Cardiac function including heart rate, coronary flow, aortic flow, and left ventricular developed pressure were recorded. After 60 min and 120 min reperfusion, 2 mg/kg of dexamethasone significantly improved the postischemic recovery of aortic flow and left ventricular developed pressure from their control values of 10.7 +/- 0.3 ml/min and 10.5 +/- 0.3 kPa to 22.2 +/- 0.3 ml/min (p < 0.05) and 14.3 +/- 0.5 kPa (p < 0.05), 19.3 +/- 0.3 ml/min (p < 0.05) and 12.3 +/- 0.5 kPa (p < 0.05), respectively. Heart rate and coronary flow did not show a significant change in postischemic recovery after 60 or 120 min reperfusion. In rats treated with 0.5 mg/kg of actinomycin D injected i.v., one hour before the dexamethasone injection, suppressed the dexamethasone-induced cardiac protection. Electrocardiograms were monitored to determine the incidence of reperfusion-induced ventricular fibrillation. Dexamethasone pretreatment significantly reduces the occurrence of ventricular fibrillation. Cytochrome c release was also observed in the cytoplasm. The results suggest that the inhibition of cytochrome c release is involved in the dexamethasone-induced cardiac protection.     

Anti-arrhythmic effect of tetrodotoxin in the late stage of experimental myocardial infarct]

The action of tetrodotoxin (TT), blocking the fast sodium current, on arrhythmias that occurred 24 hours after occlusion of the coronary artery was studied in 10 dogs. TT injected intravenously in doses of 0.5--3.0 micrograms/kg significantly decreased the number of ventricular extrasystoles, and completely restored sinum rhythm in 4 animals. The maximum antiarrhythmic effect was noted 3 to 5 minutes after TT adminstration. It is suggested that arrhythmias and the antiarrhythmic effect of the drugs in the late stage of myocardial infarction are connected with the fast inward sodium current.     

Late potentials in an ovine model of acute transmural myocardial infarction.

The development of slow conduction during the first hours of acute transmural myocardial infarction (ATMI) was studied by signal-averaged electrocardiograms (SAE) in 19 adult anesthetized sheep. SAEs were recorded before and after intravenous infusions of lidocaine and bretylium were begun and 10, 30, and 60 min after ATMI produced by ligation of the left anterior descending and second diagonal coronary arteries. Four sheep died promptly of ventricular tachyarrhythmias; two others developed sustained ventricular arrhythmias, which precluded additional data. Biphasic changes in QRS duration, root mean square voltage of the terminal 40 ms of the QRS complex, and duration of terminal low-amplitude (less than 30 microV) signal were observed. Peak changes in conduction occurred 30 min after infarction and regressed toward baseline thereafter. At 30 min, all animals developed late potentials, which were defined as signals that exceeded both after-drug QRS duration and duration of terminal low-amplitude signal less than 30 microV by more than two standard deviations. At 60 min, only 3 of 13 (23%) animals had late potentials. Conduction is slowest 30 min after ATMI in sheep but may not be related to development of ventricular arrhythmias. In five of six sheep (83%), ventricular arrhythmias occurred within 15 min of infarction before peak slowing was observed by SAE.     

Lack of relation between venous plasma total catecholamine concentrations and ventricular arrhythmias after acute myocardial infarction.

Electrocardiographic tracings were recorded continuously to monitor ventricular tachycardia and R-on-T and R-on-apex-T ventricular premature beats, and repeated estimations of venous plasma total catecholamine concentrations were carried out in 26 patients admitted to a coronary care unit with acute myocardial infarction. No relation existed between the increased catecholamine concentrations found in these patients and the incidence of ventricular arrhythmias occurring six to 48 hours after the onset of symptoms.     

Exercise capacity, energy metabolism, and beta-adrenoceptor blockade. Comparison between a beta 1-selective and a non-selective beta blocker

The effects of beta 1 and beta 1/2 blockade on exercise capacity were studied in 9 healthy normotensive subjects. Progressive maximal bicycle ergometer tests, followed by an endurance test at 80% of maximal work load, were performed during randomized, double-blind 3 day treatment periods with placebo, atenolol (beta 1) and oxprenolol (beta 1/2). The reduction of maximal work capacity (ca. 10%) was similar with atenolol and oxprenolol, despite a more pronounced maximal heart rate reduction with atenolol (from 175 +/- 2 to 132 +/- 3 beats.min-1) than with oxprenolol (to 138 +/- 2 beats.min-1). Exercise time during the endurance test was reduced from 36 +/- 4 min with placebo to 27 +/- 3 min with atenolol (p less than 0.05) and 24 +/- 3 min with oxprenolol (p less than 0.01) (atenolol vs. oxprenolol: p less than 0.05). During the endurance test, plasma glycerol and non-esterified fatty acid concentrations were reduced with both atenolol and oxprenolol. The glycerol reduction was more pronounced with oxprenolol than with atenolol, plasma NEFA concentrations being similar. Plasma glucose and lactate concentrations were reduced by oxprenolol but not with atenolol. These data show that submaximal exercise capacity at work loads representing similar relative exercise intensities is reduced during non-selective and beta 1-selective beta blockade. This reduction may be related to the effects of beta 1 blockade on energy metabolism, with possibly an additional effect of beta 2 blockade.     

Relationship between myocardial amiodarone concentration and antiarrhythmic effect in dogs with myocardial infarction and electrically induced ventricular arrhythmias

The relationship between the antiarrhythmic effect of amiodarone and its myocardial concentration was studied in dogs with 1-week-old myocardial infarction and reproducibly inducible sustained ventricular tachycardia or ventricular fibrillation. Three groups of animals (n = 10/group) received amiodarone, 40 mg.kg-1.day-1 (low-dose amiodarone), amiodarone 60 mg.kg-1.day-1 (high-dose amiodarone), or no amiodarone (control group). After 1 week of treatment, programmed electrical stimulation was repeated, and plasma and myocardial amiodarone and desethylamiodarone concentrations were measured. In the control group, sustained ventricular tachycardia or ventricular fibrillation was induced in six dogs (p = NS) when compared with baseline data. In the low-dose amiodarone group, sustained ventricular tachycardia or ventricular fibrillation was induced only in two dogs after 1 week of treatment (p less than 0.01 vs. baseline data). Sustained ventricular tachycardia or ventricular fibrillation was induced in seven dogs after treatment with high-dose amiodarone (p = NS vs. baseline data). Plasma amiodarone concentration in the low-dose amiodarone group (2.54 +/- 1.95 micrograms/mL) was significantly less (p less than 0.01) than that in the high-dose amiodarone group (4.64 +/- 1.66 micrograms/mL). Similarly, the plasma desethylamiodarone in the low-dose amiodarone group (0.32 +/- 0.16 microgram/mL) was significantly less (p less than 0.001) than that in the high-amiodarone dose group (0.56 +/- 0.23 microgram/mL). The myocardial amiodarone concentration in the low-dose amiodarone group (49.7 +/- 23.1 micrograms/g) was significantly lower (p less than 0.001) than that in the high-dose group (98.4 +/- 32.1 micrograms/g).(ABSTRACT TRUNCATED AT 250 WORDS)     

Inhibition of mitochondrial permeability transition improves functional recovery and reduces mortality following acute myocardial infarction in mice

Inhibition of mitochondrial permeability transition pore (mPTP) opening by cyclosporin A or ischemic postconditioning attenuates lethal reperfusion injury. Its impact on major post-myocardial infarction events, including worsening of left ventricular (LV) function and death, remains unknown. We sought to determine whether pharmacological or postconditioning-induced inhibition of mPTP opening might improve functional recovery and survival following myocardial infarction in mice. Anesthetized mice underwent 25 min of ischemia and 24 h (protocol 1) or 30 days (protocol 2) of reperfusion. At reperfusion, they received no intervention (control), postconditioning (3 cycles of 1 min ischemia-1 min reperfusion), or intravenous injection of the mPTP inhibitor Debio-025 (10 mg/kg). At 24 h of reperfusion, mitochondria were isolated from the region at risk for assessment of the Ca(2+) retention capacity (CRC). Infarct size was measured by triphenyltetrazolium chloride staining. At 30 days of reperfusion, mortality and LV contractile function (echocardiography) were evaluated. Postconditioning and Debio-025 significantly improved Ca(2+) retention capacity (132 +/- 13 and 153 +/- 31 vs. 53 +/- 16 nmol Ca(2+)/mg protein in control) and reduced infarct size to 35 +/- 4 and 32 +/- 7% of area at risk vs. 61 +/- 6% in control (P < 0.05). At 30 days, ejection fraction averaged 74 +/- 6 and 77 +/- 6% in postconditioned and Debio-025 groups, respectively, vs. 62 +/- 12% in the control group (P < 0.05). At 30 days, survival was improved from 58% in the control group to 92 and 89% in postconditioned and Debio-025 groups, respectively. Inhibition of mitochondrial permeability transition at reperfusion improves functional recovery and mortality in mice.