Colin L. Bray

Early intravenous atenolol treatment in suspected acute myocardial infarction. Preliminary report of a randomised trial.

214 patients were studied in a randomised trial to determine whether administraiton of intravenous atenolol within 12 hours of chest pain reduced eventual infarct size, as estimated by cumulative enzyme release and by ECG changes. 135 patients already had ECG evidence of infarction at entry; 72 received atenolol which significantly decreased subsequent enzyme release (atenolol and control means = 121 IU, SE +/- 10 and 177 IU, SE +/- 17; 2p < 0.005) and enhanced R-wave preservation (atenolol and control means = 46% +/- 3 and 36% +/- 3; 2p < 0.02). 79 patients had no evidence of infarction at entry; 44 did not receive atenolol and 27 of these subsequently developed infarction, whereas only 11 of 35 treated patients infarcted during their hospital stay (2p < 0.01). In hospital, fewer atenolol patients died (4 vs 9), had non-fatal cardiac arrests (2 vs 6), or required therapy for heart-failure (36 vs 47). Unlike many previous trials which had negative results, in this trial we gave the drug intravenously and promptly (median of 4 hours from onset of pain to injecton), thereby achieving early beta-blockade.

Plasma-catecholamines after cardiac infarction.

Abstract Plasma noradrenaline and adrenaline were measured in fifty men after cardiac infarction and in fifty controls. Noradrenaline levels were significantly higher in the cardiac patients compared with the controls, but adrenaline levels were similar in the two groups. The catecholamine levels were analysed for the patients in relation to the incidence of dysrhythmias. Compared with patients who had no complications, patients with atrial dysrhythmias or early ventricular dysrhythmias had higher noradrenaline concentrations in their plasma. There was no such difference for patients with late ventricular dysrhythmias, and adrenaline levels were unremarkable. The raised noradrenaline levels are not thought to be related to stress because six other patients undergoing the stressful procedure of cardiac catheterisation had low levels. High noradrenaline levels in three racing drivers shortly after a race suggest that the beta-adrenergic effect of noradrenaline does not lead to ventricular dysrhythmias in the presence of a healthy heart. It is concluded that there is an increased noradrenaline release after myocardial infarction and that this is related to the development of serious dysrhythmias.

Ischemic pain relief in patients with acute myocardial infarction by intravenous atenolol

Pain relief in acute myocardial infarction (AMI) by the beta-adrenoceptor antagonist, atenolol, was demonstrated by three separate studies. First, 18 patients were randomized to double-blind intravenous atenolol (5 mg) or saline immediately after admission, followed by oral atenolol (50 mg) or placebo 10 minutes later. In patients receiving atenolol, pain relief coincided with reduction in heart rate (HR), systolic blood pressure (SBP), and HR X SBP product (p less than 0.05); however, pain and these parameters were unchanged by placebo. The degree of pain relief was related to the reduction in cardiac work achieved (r = 0.725; p less than 0.001). A second open study involving 22 patients receiving intravenous atenolol (5 to 15 mg) early after AMI showed ischemic pain relief in 17 patients. They achieved a more significant reduction in HR X SBP product than those whose pain remained unchanged (p = 0.004). Finally, a retrospective study of 163 patients randomized to either atenolol or no beta blockade early after AMI revealed that patients receiving atenolol needed less opiate analgesia after admission (p less than 0.001). The safety of this therapy was illustrated by a decreased incidence of left heart failure and atrial fibrillation and no tendency to second- and third-degree heart block.

Reduction in Infarct Size, Arrhythmias, Chest Pain and Morbidity by Early Intravenous β-Blockade in Suspected Acute Myocardial Infarction

Summary477 patients suspected of acute myocardial infarction, with onset of less than 12 hours, were randomised to a control group or a group receiving intravenous atenolol followed by oral treatment for 10 days. In patients with electrocardiographic (ECG) changes of infarction at entry, intravenous atenolol significantly reduced enzyme release by one- third and enhanced R wave preservation. In patients without ECG changes of infarction at entry, treatment significantly prevented the development of infarction in a proportion of patients.There was also a significant reduction in R- on- T ectopics, repetitive ventricular arrhythmias and supraventricular arrhythmias. Treated patients had greater pain relief and required less opiate analgesics. Fewer atenolol- treated patients died at 1 week, had non- fatal cardiac arrests, developed heart failure, or suffered reinfarction.

Thallium-201 myocardial imaging in patients with angina pectoris and anomalous aortic origin of the circumflex coronary artery

Anomalous aortic origin of the circumflex coronary artery is the commonest coronary artery anomaly. In this study, the significance of anomalous aortic origin of the circumflex coronary artery was investigated in seven patients with exertional chest pain using exercise thallium scintigraphy. Five patients with circumflex coronary arterial disease served as controls. Myocardial perfusion was normal in the five patients with a nonstenosed anomalous artery. In these patients, exercise heart rate and blood pressure response were normal. Two patients with a stenosed anomalous circumflex coronary artery and four of the five control patients had posterolateral myocardial perfusion defects. It is concluded that anomalous aortic origin of the circumflex coronary artery does not cause impairment of myocardial perfusion unless it is the site of significant coronary arterial stenosis.

Accelerated atherosclerosis and myocardial infarction complicating anomalous origin of the right from the left coronary artery

A patient is described in whom a previously unstenosed single coronary artery was complicated 12 months later by anterior myocardial infarction. Full clinical features documented by exercise thallium scintigraphy and coronary angiography before and after myocardial infarction are described.

Actuarial analysis of late results after closed mitral valvotomy

The long-term results of closed mitral valvotomy performed between 1978 and 1985 in 198 patients with noncalcific mitral stenosis were analyzed. Follow-up data were available on 185 patients (93%); 1 patient died in the postoperative period, and 12 foreign patients were lost to follow-up. At the 4-year and 8-year intervals, 91% and 80% of patients, respectively, were event free (not in need of further operative procedures). By multivariate analysis, the factor preoperative mild mitral regurgitation showed a tendency to influence the event-free period. By univariate analysis, postoperative mitral regurgitation significantly reduced the event-free period. Twenty-one patients subsequently underwent mitral valve replacement; 8 for mitral regurgitation, 10 for mitral stenosis, and 3 for mixed mitral regurgitation and stenosis. By multivariate analysis, the reason for reoperation significantly influenced the length of the event-free period. The patients with mitral regurgitation required mitral valve replacement sooner than those with mitral stenosis. Advanced age, sex, previous valvotomy, preoperative New York Heart Association Functional Class, low mitral valve leaflet excursion, and pulmonary hypertension had no influence on the long-term result.

Comparison of once and twice daily oral dosing schedules of bevantolol, a new β-adrenoceptor antagonist with α-adrenoceptor partial antagonist activity in patients with angina of effort

In a placebo controlled double-blind cross-over study following a dose titration phase, we compared the efficacy of benantolol, a new beta 1 adrenoceptor antagonist with alpha-adrenoceptor partial antagonist activity at 12 and 24 hours after dosing in patients with angina of effort. Twenty patients aged 43-65 years were studied. Each study phase lasted four weeks. Efficacy was determined by treadmill exercise testing using the standard Bruce protocol at the end of each phase. Fifteen patients satisfactorily completed the study. Data from five protocol violators were not analysed. In the four patients who received bevantolol 200 mg daily, exercise time increased from 395 +/- 192 (mean +/- 1 SD) sec on placebo to 468 +/- 171 sec at 10-12 hours and to 442 +/- 230 sec at 22-24 hours after dosing with bevantolol. In the eleven patients who received bevantolol 400 mg daily, exercise tolerance of 290 +/- 103 sec on placebo increased to 408 +/- 112 sec at 10-12 hours (P = 0.001) and to 400 +/- 98 sec at 22-24 hours (P = 0.001) after dosing with bevantolol. Maximum exercise capacity at 10-12 and 22-24 hours after dosing with bevantolol were comparable. Maximum exercise heart rate and systolic blood pressure on placebo and on bevantolol at 10-12 and at 22-24 hours after dosing were comparable. Thus, bevantolol has salutary effects on exertional angina up to 24 hours after dosing.