The deaths of IOO men due to coronary artery disease which occurred so suddenly and unexpectedly as to merit a coroner's necropsy have been studied, with special reference to the exact circumstances of their occurrence. I973) have shown that in nearly could be considered to be causally related to the every case severe coronary atheroma will be found, deaths and to the post-mortem findings in the heart. but that very many fewer will show evidence of For this purpose ioo consecutive such deaths in recent coronary thrombosis or myocardial infarcNewcastle upon Tyne were taken. They were tion, or both. It is by no means certain that when sufficiently sudden and unexpected as to be referred neither has been found neither has been present, to the coroner, and because of this referral, nec-for thrombi may disintegrate or lyse after death ropsies were performed in every instance. It was and infarcts may be too fresh to be recognizable from his office and with his co-operation that the by any staining method. Spain and Bradess (I970), names and addresses were obtained. All the ioo however, from careful studies sometimes made as cases fulfilled the WHO definition of sudden death early as I5 minutes after death, concluded that this as death occurring within 24 hours of the onset of was not a likely explanation and noted that in the acute symptoms. The duration of symptoms before sudden cases where an infarct but no thrombus death was as follows: none (instantaneous), 34; less had been found the infarct was usually multifocal than I5 minutes, 20; I5 minutes to one hour, I9; and subendocardial, whereas when a thrombus was more than one hour, 27. In only eight of the cases present the infarct was unifocal and transmural. was there time for help to be obtained.Consistent with this are the observations of Haerem The necropsy provided evidence on whether (I97i), recorded after this investigation had begun, there had been coronary thrombosis or myocardial that many patients who died suddenly and unexpectedly had platelet aggregates occluding their Received 28 April I975.intramyocardial vessels. Presumably in the presence 1 Present address: Royal Free Hospital, London. of a circulation slowed by coronary stenoses factors

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. med. J3., 1964, 2, 724-725 Blockade of adrenergic beta-receptors has a possible application in the management of angina of effort, presumably through reduction of exercise-induced tachycardia and thereby of total cardiac work. A clinical trial with pronethalol has shown encouraging results (Alleyne et al., 1963). Its further use has, however, been limited partly by frequent central-nervous-system side-effects and partly by its carcinogenic action on mice (Paget, 1963).Propranolol (I.C.I. 45520, Inderal), a newly developed agent with a similar mode of action, has been shown to have a therapeutic effect about 10 times greater than that of pronethalol but without demonstrable carcinogenic potential (Black et al., 1964). The results of its use in a double-blind trial in) cases of angina of effort are reported. Material and MethodsTwenty-two patients (15 males and 7 females) were selected for the trial. They all had classical angina of effort, occurring several times a day. The history of their angina varied considerably, ranging from three months to 15 years, with an average of three years, but the severity of their symptoms had remained almost unchanged for at least two months before the start of the trial. Ten patients had sustained previous myocardial infarction. All 22 subjects had electrocardiographic evidence of ischaemic heart disease at rest.Patients attended the hospital at the beginning of the trial and at the end of two successive periods of three weeks each, and were seen by the same member of the team. Each patient was asked to keep a " progress card " and to note on it at the end of each day the number of anginal attacks, the number of TNT tablets taken to relieve them, and whether the pain that day had been the same as usual, worse, better, or absent. At each attendance the patients were examined and their general well-being, body weight, heart rate, and blood-pressure recorded. They also had electrocardiograms taken and specimens were collected for urine analysis, white-cell count, and haematocrit, and for liver-function tests, including serum transaminase and paper electrophoresis. At the interview concluding each threeweek period of treatment they were asked to give their own opinion of the effect of the treatment upon their angina and were questioned about any side-effects.The double-blind trial was arranged so that the patients received the drug and placebo tablets for a three-week period each in a random order. The drug was prescribed in 10-mg. tablets in a standard dosage of one tablet three times a day for three days and thereafter increased to two tablets three times daily. If side-effects developed the patients had instructions not to discontinue the tablets but to reduce the dose to four tablets a day and to seek an early interview. pronethalol, which had been found effective in a daily dose of 300-400 mg. The corresponding dose of 30-40 mg. of propranolol could have been employed, but a slightly higher dose was preferred in order to assess the frequency and nature of possible side-eff...

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