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In recent years the widely held concept that coronary thrombi cause myocardial infarcts has been seriously questioned. On the basis of pathologic studies, several reports have suggested that coronary thrombi do not cause infarcts but instead are the result of infarction. Should these findings become generally substantiated, the antithrombotic approach to the prevention and therapy of ischemic heart disease must be revised. This workshop was organized to examine more closely this issue and to sort out reasons for such divergent views of the role of thrombosis in the pathogenesis of myocardial infarction.

Summary The coronary arteries of 47 sudden coronary death patients and 34 control patients were examined post mortem in order to analyse pathogenetic factors of sudden coronary death. Mural platelet microthrombi prevailed in patients who had died suddenly and unexpectedly of coronary disease, and more in those who had died some minutes after onset of symptoms than in those who had died instantly. It is suggested that reactive platelets might be of pathogenetic importance in sudden coronary death. Reactive platelets would form mural platelet microthrombi, and, as described in previous reports, platelet aggregates in the coronary vessels. Myocardial ischemia caused by occlusive platelet aggregates in intramyocardial vessels could result in sudden death. In 32 sudden death patients the larger coronary arteries supplying the sinus-and atrioventricular nodes were examined for acute major lesions (thrombi, ruptures of necrotic plaques, occlusive intimal hemorrhages, and emboli). In 12 patients a major acute lesion upstream to one or both of the conduction nodes was observed. It was concluded that acute major lesions in the larger arteries supplying the sinus-or atrioventricular nodes could be a cause of sudden coronary death, but did not appear to predominate as a cause of sudden death.

The relationships between the following were examined in 100 patients who died within 25 days after presenting with clinical and pathological evidence of a myocardium infarction: frequency of acute coronary occlusion, degree and length of old fibrous-atheromatous stenosis at the site of eventual coronary occlusion, size, type, and location of the infarct, size of pre-existing scars, weight of the heart, irreversible shock, and anticoagulant therapy. In 62 cases no acute occlusive lesion was present, while in 38 cases an occlusive thrombus was found always located at the site of an old severe stenosis. The presence of the thrombus correlated with the increasing size of the infarct, the increasing length of the pre-existing stenosis. The present findings support the hypothesis that the thrombus is a secondary phenomenon related to flow redistribution by collateral vessels in stenosed arteries.

The frequent association of hyperglycemia and coronary thrombosis has long been recognized. However, the significance and pathogenesis of this finding, and the possible relationship to diabetes mellitus have been obscure. The present study was undertaken in an attempt to clarify the problem.

The occurrence rate of coronary thrombosis and myocardial infarction as well as venous thrombosis and pulmonary thromboembolic phenomena are extremely low in indigenous East Africans as compared with corresponding occurrence rates among Caucasians in the United States. Differences in occurrence rates could be due to differences in degrees of atherosclerosis (local factor) or to differences in the clotting properties of the blood (hematologic factor) or both. In the current study, in an attempt to obtain some insight into the mechanisms accounting for differences in the two population groups, we have investigated various factors related to coagulation and clot-lysis in plasma obtained from two groups of indigenous East African males, a medical student group with ages ranging from 20 to 30 years, and an outpatient group aged 30–60 years; and have compared these factors with corresponding factors in age-matched groups of New York males. Plasma fibrinogen and prothrombin levels of the two East African groups were significantly lower than those of the two age-matched corresponding New York groups. A definite increase in fibrinogen levels with age was noted in both East Africans and New Yorkers, and the binding power in the thrombelastograph was directly proportional to the fibrinogen levels. Euglobulin lysis times of the East African groups were significantly shorter than those of the age-matched corresponding New York groups. The thrombelastographic study was carried out only on the two medical student groups, and the clot-lysis times of the East African medical student group were significantly shorter that those of the New York medical student group. To what extent these significant differences in fibrinogen and prothrombin levels and clot-lysis times in the East African and New York groups account for the significant differences in the incidence of thromboembolic phenomena is difficult to determine. Higher values for various coagulation factors and prolonged lysis times do not necessarily mean a hypercoagulable state, and many more aspects of thrombogenesis must be assessed before causal mechanisms can be elucidated.

An affection of the shoulder characterized by pain, muscle spasm, and limitation of motion occurs commonly in patients with angina pectoris. With rare exceptions the left shoulder is involved when there is left-sided radiation of anginal pain; the right shoulder when there is right-sided radiation. This shoulder pain is continuous, is not exaggerated by factors that usually induce anginal pain, but is often aggravated by sudden progress of the heart lesion, such as coronary thrombosis or acute left ventricular failure. Such shoulder pain does not call for bed rest and treatment of the heart, but is relieved by local physiotherapeutic measures. At times the Libman maneuver-firm pressure on the homolateral brachial plexus-brings about instant relief of this pain and limitation of motion. The mechanism of this shoulder pain remains obscure. Certain analogies suggest that the radiation of the anginal pain to the shoulder superimposed on a local slightly painful affection of the shoulder may by summation induce this painful disablement. However, the many other trophic and sensory disturbances that may occur in the left upper extremity in patients with angina pectoris, suggest rather that the chief factor lies in some reciprocal relationship between afferent impulses from the heart and sensitization of the neurones whose fibers go to make up the brachial plexus. The site and radiation of anginal pain may be determined by extracardiac lesions, such as abscesses of the teeth or spondylitis. In such cases the anginal pain may be experienced only or chiefly in the area sensitized by somatic disease. Conversely in the presence of peptic ulcer or of gall bladder disease the pain arising in the ulcer or in the gall bladder may follow the anginal radiation. Fitz-Hugh and Wolferth's observation is confirmed that there are patients with gall bladder disease, with reference of the pain to the precordium and T-wave changes in the electrocardiogram, in whom operative removal of the gall bladder is follwed by disappearance of precordial pain and a return to normal of the electrocardiogram.

An unusual case of pulmonary embolism from unrecognized and asymptomatic pelvic phlebitis in a previously healthy male of thirty-three years is reported. Accurate electrocardiographic examination with especial reference to Lead IV may be of great importance.

The system of detection of unwanted side effects in new drugs distributed to the general public is described with several specific drugs cited including reference to the effects of oral contraceptives (OCs) and the manner in which their connection to thromboembolic phenomena was established. Attempts to estimate the incidence of thromboembolism by women using OCs from reports to the Committee on Safety of Drugs proved unsatisfactory. 3 separate studies however were found to give evidence in support of the relationship. 1 study interviewed young women recorded in the diagnostic index as having attended for a new episode of vascular pulmonary embolism or venous cerebral or coronary thrombosis of women who had no predisposing cause for the disease. In the 3rd study prepared for the Committee on Safety of Drugs all the deaths that had occurred in England Wales and Northern Ireland during 1966 in women 20-44 years old in which thrombosis or embolism of the pulmonary cerebral or coronary vessels was referred to on the death certificate were enumerated. The results showed the risks of developing deep vein thrombosis pulmonary embolism or cerebral thrombosis in the OC user 8 times that of the nonuser and the risks of developing phlebitis 3 times as great in the OC user. Pharmacological experience and knowledge of the mechanisms by which drugs act should enable many effects to be predicted. A system of medical intelligence such as mortality statistics can provide information on trends. It is suggested that a system of record linkage by computer is needed and that early warning system of the effect of new drugs should be limited to unusual or severe effects. Another suggestion encompasses use of the practitioners prescription as a method of monitoring the patients at risk from a new drug.

A brief report of observations on the relief of anginal pain, obtained by improving the movements of the diaphragm and presumably acting through more adequate filling of the heart and coronary vessels, is submitted. A positive means of prevention and treatment of anginal pain in the group of patients who are potential or actual sufferers from the syndrome is offered in the form of an elastic abdominal support supplemented by dietary restriction. It is probable that by these means the common catastrophe of coronary thrombosis may be postponed. While the great majority of persons who suffer from angina pectoris are obese, we have noted that a lighter type of elastic belt affords complete relief to the few individuals of slender build with the same syndrome. The elastic belt obviously can be of no value if the diaphragm is fixed through disease. At the moment, the methods described would appear to be of distinct value to those who appear with well-established symptoms. However, if we are to prevent or postpone the development of the syndrome, we must apply this knowledge to the large group of sedentary workers, chiefly males, who are given to indulgence in good food beyond their needs. If our experience is duplicated by that of other clinicians, the way may be found to lessen the mounting toll of deaths in this group during middle life and beyond. It is suggested that this approach to an understanding of problems concerned with the coronary circulation will have an application in the study of the arterial supply to other organs, especially to the brain, which in patients in this group is likely to be the seat of vascular accidents. At a later date case histories and details of the studies that are now under way will be reported.

The medical-legal importance of acute coronary occlusion in industry was discussed in a previous paper. 1 This study is concerned particularly with the reaction of the heart to indirect injuries caused by exposure to toxic fumes, electricity, infections, and foreign proteins. The patients were workers (except Case 6) who applied for compensation benefits, believing that certain incidents which had occurred because of, and during the course of, employment had caused acute heart disease. The most common diagnosis was acute coronary occlusion, although a better diagnostic term would have been acute toxic myocarditis or coronary circulation insufficiency. These clinical impressions rested on a varying combination of first recorded medical observations, a careful history, the examination, the subsequent clinical course, and the electrocardiographic, roentgenographic, and laboratory findings. It can be safely stated that in all injuries the amount of damage is usually in direct proportion to the offending force and that the physical status of an organ determines its response to trauma.

A review is presented of 107 cases of paroxysmal ventricular tachycardia. In the majority it was associated with acute coronary thrombosis or coronary sclerosis, in some with rheumatic valvular disease, and in others with no organic heart disease. It is generally critical and demands careful attention. Occasional cases are overlooked because only one heart sound is present for each cardiac cycle and the heart rate is misjudged to be one-half the actual rate. The outlook often is serious if the condition is not effectively treated. Therapy generally is successful in controlling the arrhythmia. The most valuable drug is quinidine. Other medications are magnesium sulfate, atropine, potassium salts, and possibly morphine.

Not all patients with acute coronary thrombosis or inadequacy develop classic myocardial infarction. Almost 30 per cent of such patients were found to have atypical and apparently less extensive myocardial injury as estimated by the clinical and electrocardiographic findings. The morbidity as well as the mortality was of a lesser order and a somewhat different therapeutic regimen could be employed.

Summary1. Serum transaminase and lactic dehydrogenase levels are excellent tests for detecting tissue necrosis. They can contribute to the diagnosis of myocardial infarction, especially cases where the diagnosis cannot be firmely established on clinical and/or electrocardiographic grounds.2. Only repeated dosages, with the construction of a dosage-time curve, are of diagnostic value (38). A sharp increase in serum enzyme levels followed by a progressive return to normal indicates coronary thrombosis while permanently high values suggest a lesion in some other organ (fig. io). A secondary increase in serum enzyme levels (especially DL) in the course of myocardial infarction is usually due to necrosis within some other tissue (23,24,25,27,29).

The effect of the vascular spasm on the function of the anticoagulating system of the blood was studied in experiments on rabbits. Intravenous injection of thrombin solution (4g) into healthy animals did not provoke thrombosis; on the contrary, the blood lost its ability to coagulate. However the same dose of thrombin together with 0.5 ml of pituitrin resulted in the rapid formation of intravascular thrombi causing coronary thrombosis and myocardial infarction. A study was made of the extent of the possible action of the anticoagulation system in myocardial infarction which was induced by ligation of the coronary arteries. The administration of 4g of thrombin induced a repeated infarction, and thrombosis in various parts of the vascular system. It was concluded that; a) The anticoagulation system of the blood becomes disturbed during vascular spasm, so that there is an increased tendency to intraction may occur without changes in the walls of the coronary vessels only when there is spasm which causes an increase in the tendency of the blood to coagulate. Myocardial infarction itself will after the anticoagulatory system of the blood, so that intravascular thrombus formation may be induced by small doses of thrombin administered alone.

Summary These were damage of the arterial wall caused by calciferol, blood hypercoagulability caused by feeding butter and acute haemodynamic changes caused by adrenaline and ecolid (chlorisondamine). Spontaneous occluding thrombi were produced in the coronary arteries with resultant cardiac infarcts in 2 animals receiving calciferol-butter-adrenaline and in 4 receiving calciferol-butter-ecolid.

1.1. Biopsy studies of immediate and delayed skin reactions to tobacco and saline control wheals were studied in 10 patients with thromboangiitis obliterans, one of migrating phlebitis, and one with acute coronary thrombosis. 2.2. Eosinophiles, varying in numbers, were found in the histologic sections of the immediate urticarial wheals produced by the tobacco allergen in 6 of 8 cases of thromboangiitis obliterans and in one case of migrating phlebitis. 3.3. The biopsies of 2 patients with thromboangiitis obliterans and one 37-year-old patient with coronary artery thrombosis, who developed delayed reactions, showed an acute dermatitis. 4.4. The exciting role of tobacco in the 12 cases studied was corroborated clinically by arrest in the progress of symptoms following cessation in the use of tobacco. In one patient (Case 9) giving a delayed eczematous type of local reaction, a generalized eczema and exacerbation of the symptoms of thromboangiitis obliterans were induced by repeated subcutaneous injections of tobacco extract.

An interesting case of coronary thrombosis in an 8-year-old female ape, in which the clinical signs, type of death, and pathologic changes in the heart were comparable to those in human cases of fatal coronary thrombosis, has been observed and described.

The literature dealing with changes in the coronary arteries as shown by post-mortem examinations of instances of Buerger's disease is reviewed, and thirty such eases are recorded. The lesions in the coronary arteries vary from simple intimal thickenings to severe arteriosclerosis and coronary thrombosis. In four instances the belief was expressed that the coronary lesions were characteristic of thromboangiitis obliterans. In none of these, however, was there given a clear-cut description of the coronary lesions or illustrations showing the characteristic lesions. An instance of sudden death is reported. The patient had shown clinical evidence of Buerger's disease but no evidence of cardiac lesions. The autopsy revealed severe thromboangiitis obliterans of the coronary vessels, coronary arteriosclerosis, multiple small infarcts and fibrosis of the myocardium. Sections of the coronary arteries showed, in addition to uncomplicated lesions of thromboangiitis obliterans, a combination of thromboangiitis obliterans and arteriosclerosis. Because of these findings and because of the fact that, according to the pertinent literature, coronary arteriosclerosis was found rather frequently in relatively young patients afflicted with Buerger's disease as proved by autopsy, the question of the relation between these two diseases is discussed, and the possibility is considered that a primary inflammatory lesion of the artery may be at least one factor in the causation of arteriosclerosis. Syphilitic arteritis, rheumatic arteritis, and also thromboangiitis obliterans may each constitute the primary inflammatory factor.

T ;IE r6le played by syphilis in the etiology of angina pectoris, coronary sclerosis and thrombosis, and of cardiac infarction has never been clearly evaluated ; and varying opinions have been held by clinicians as to its importance in the production of these conditions. The most recent writers, as Levine, believe that syphilis is rarely an underlying factor in the causation of coronary thrombosis. In only three of Levine’s eighty-nine cases in which a Wassermann reaction was done was there a positive reaction, and in one other case with a negative reaction, there was a history of a primary infection. From this it would appear that only 4.5 per cent of his patients were syphilitic, and it does not necessarily follow that in these cases the syphilis was the etiologic factor in the production of coronary thrombosis. In one case only, a patient only thirty-six years old, the youngest in his series, did this seem likely. In the other cases the syphilis may well have been coincidental. Levine decides that coronary thrombosis and myocardial infarction are rarely caused by syphilis. However, in Levine’s cases the diagnoses were chiefly clinical and gross pathological. In only forty-six of the cases were autopsies done, and t,he microscopic diagnosis of syphilis does not seem to have been considered. It is possible that microscopic criteria for the diagnosis of syphilis might have increased the percentage of syphilitics in his material. In thirteen autopsies on patients dying of coronary disease reported by W. J. Stone, microscopical examination showed syphilitic periarteritis in two cases. In eighty-six autopsies of coronary sclerosis, Willius and Brown found syphilis of the aorta in 19 per cent.

SummaryThe roles played by the blood clotting system and by fibrinolysis in the haemostatic balance are discussed. The significance of the tissue thromboplastin and the tissue activator of plasminogen for local haemostasis is emphasized, and their relation to anticoagulant therapy considered. Problems specific for coronary thrombosis, cerebral thrombosis and cerebral haemorrhage have been mentioned.

1. 1. Due to the more common use of the electrocardiograph instances of paroxysmal bundle-branch block are becoming a more frequent finding. It is important to recognize the fundamental cause of the branch block in these cases and to differentiate clearly the inconsequential type from the group in which changes in the junctional tissue incident to heart disease are primarily responsible for the conduction disturbances. 2. 2. The former group consists mainly of cases in which the QRS complex is wide and the P-R interval is abnormally short (Wolff, Parkinson, and White). This finding is no indication of heart disease. 3. 3. Significant are the cases in which changes in the conduction tissue are a direct or indirect result of organic heart disease. Pathological processes, not necessarily permanent, in a branch of the bundle of His such as are associated with myocardial failure, coronary insufficiency, and coronary thrombosis, with or without partial fibrosis of a branch, are primarily responsible for transient or recurrent bundle-branch block. Although physiological changes may act as precipitating factors it should be recognized that these are effective only in the presence of actual changes in the conducting tissue. It is doubtful whether an acute infectious process other than diphtheria can cause transitory branch block; perhaps very rarely a rheumatic infection may so act. 4. 4. Fifty-eight cases of paroxysmal bundle-branch block were found reported in the literature and to these we have added thirteen new cases. Of the seventy-one patients these was clear evidence of heart disease in sixty-five, of which thirty-five were males, twenty-nine were females, and one was of unrecorded sex. The six patients without other evidence of heart disease are excluded from the analysis although we consider the presence of paroxysmal bundle-branch block in itself evidence of heart disease. Coronary or hypertensive heart disease was present in forty-four patients while chronic rheumatic heart disease was present in six. The etiology of the heart disease in the remaining fifteen patients was diphtheria in four; thyrotoxicosis in three; congenital in one; and obscure in seven. Left bundle-branch block was present in sixty of the sixty-five patients. Moderate to severe heart failure was associated with the branch block in twenty-five patients. 5. 5. The effects of changes in vagal tone were studied in six of our cases. Single bundle-branch block complexes were obtained during vagal stimulation on two occasions in one of these. Our experience and the published data show that increase in vagal tone does not produce sustained inhibition of bundle-branch conduction. Variations in vagal tone affect the conduction only by decreasing or increasing the cardiac rate to such an extent that the depressed branch becomes capable or incapable of transmitting impulses. 6. 6. The mechanism of “partial” or “incomplete” bundle-branch block is discussed in the light of present experience. 7. 7. We conclude that paroxysmal bundle-branch block (without a very short P-R interval) is as a rule a sign of serious heart disease, most often due to coronary sclerosis but in some cases associated with rheumatic heart disease, diphtheria, and factors that cannot clinically be ascertained. It is doubtless more common than it has been thought to be; serial electrocardiograms taken during myocardial (congestive heart) failure, coronary insufficiency, and elevated heart rates may reveal transient defects in bundle-branch conduction.