Albert J. Miller

Ventricular Aneurysm A Reappraisal Based on a Study of Sixty-Five Consecutive Autopsied Cases

Sixty-five consecutive autopsied cases of ventricular aneurysm are reviewed. The incidence of aneurysm following myocardial infarction is similar to that reported in other series. Myocardial infarction preceded the formation of an aneurysm of the ventricle in the vast majority of patients, and a new myocardial infarction was the cause of death of about 50 per cent of them. The survival rate of patients with ventricular aneurysm is not significantly different from the long-term survival of all patients with myocardial infarction found in the same institution. Complications of ventricular aneurysm such as chronic congestive heart failure and rupture of the aneurysm were infrequent causes of death, and systemic embolic phenomena were not observed as a cause of death. In only four patients was the diagnosis made ante mortem. The lack of characteristic clinical, radiologic, and electrocardiographic findings is discussed. It is suggested that the hemodynamic significance of ventricular aneurysms is not ordinarily great, in view of the unaffected statistical prognosis in its presence. The recommended indications for surgery of ventricular aneurysms, based on this retrospective study, are presented.

The production of acute pericardial effusion: the effects of various degrees of interference with venous blood and lymph drainage from the heart muscle in the dog.

Abstract Obstruction to the venous blood and lymph outflow from the heart muscle leads to the formation of a pericardial effusion originating primarily from the epicardial surface of the heart (the visceral pericardium). The degree of effusion is proportionate to the extent of interference with the venous blood and lymph flow. Pathologic changes found in the myocardium include venous and lymphatic congestion, perivascular and interstitial edema, and early myocardial necrosis. These studies have defined a method of producing an acute pericardial effusion in the dog and clarify certain aspects of the mechanism of formation of pericardial effusions. It is considered likely that all pericardial effusions, irrespective of cause, arise primarily from the epicardial surface (visceral pericardium) of the heart.

VENTRICULAR ENDOMYOCARDIAL CHANGES AFTER IMPAIRMENT OF CARDIAC LYMPH FLOW IN DOGS

The mammalian heart has an extensive lymphatic system (Patek, 1939) which has been given little attention in the published reports on cardiovascular systems. Our interest in the cardiac lymphatics was stimulated by the possibility that obstruction to their flow might cause endocardial changes. Reasoning by analogy with elephantiasis and similar conditions due to interference with lymph flow, we postulated that endomyocardial fibrosis or endocardial fibro-elastosis or both might follow chronic impairment of cardiac lymph flow. This was tested in the dog. Our preliminary studies (Miller, Pick, and Katz, 1960) established that endomyocardial changes are produced by chronic interference with the cardiac lymph flow. The present communication is a final report of a more extended series of observations in which we tested our hypothesis more precisely. This expanded survey also permitted a clearer definition of the sequence of pathological events that follow chronic impairment of cardiac lymph flow in the dog.

Ventricular Endomyocardial Pathology Produced by Chronic Cardiac Lymphatic Obstruction in the Dog

Chronic impairment of cardiac lymph flow was successfully accomplished in 22 dogs after preliminary anatomic studies revealed a feasible surgical technic. The anatomic and surgical details are presented. Gross and microscopic studies were possible in 19 of the operated animals, 3 of which died spontaneously, and 16 of which were sacrificed at varying time intervals between 2 and 16 weeks after surgery. Two of the 19 dogs were completely normal on gross and histologic examination. Abnormalities found in the remaining 17 animals included left and right ventricular subendocardial hemorrhages, increased elastic and fibrous tissue in the left ventricular endocardium, and opacification of the mitral valve leaflets. It is concluded that chronic impairment of cardiac lymph drainage is productive of significant endomyocardial pathology. These observations are considered to be important as possible etiologic mechanisms in endomyocardial fibrosis and endocardial fibroelastosis. The cardiac lymphatics merit continued intensive investigation, inasmuch as they surely have an important role in cardiac physiology and pathology. Their importance may encompass a far broader area than suggested above. They may be related to the so-called nutritional cardiopathies. The fibroplastic effects of serotonin might occur through an effect on the cardiac lymphatics. Impairment of heart lymph flow may be important in endocarditis and myocarditis of certain types, for it is known that chronic lymphatic obstruction predisposes to recurrent inflammation and infection in the affected parts.

Acute and Chronic Effects of an Adrenergic Beta-Receptor Blocking Agent (Propranolol) in Treatment of Cardiac Arrhythmias

The effects of intravenous and oral administration of propranolol, an adrenergic beta-receptor blocking agent, have been studied in 29 patients with various cardiac arrhythmias. The ventricular responses in chronic or paroxysmal ectopic supraventricular arrhythmias were decreased at rest or during exercise. Sinus tachycardias were regularly slowed. Two supraventricular tachycardias and one ventricular tachycardia, all consistently precipitated by exogenous stimuli, were prevented. Six instances of digitalis-induced arrhythmias were responsive to treatment.Propranolol, especially when given orally, is of definite value in selected disturbances of cardiac rhythm. Reasonable caution should be exercised, however, because of the risk of precipitation of congestive heart failure or hypotension in patients with limited cardiac reserves.

Lymphatics of the mitral valve of the dog. Demonstration and discussion of the possible significance.

Thin-walled vessels have been visualized histologically in the mitral valve of the dog; these vessels were increased in number and caliber in animals with chronic impairment of cardiac lymph flow. Injection of diluted India ink into the free edge of the anterior mitral leaflet of the beating heart revealed extensive networks of vessels, grossly visible on the atrial surface of the valve. Histological study showed the India ink to be within thin-walled channels. Thus, there is compelling evidence that the visualized vessels are lymphatics and that their size and number increase when the cardiac lymphatic drainage is chronically impaired. The possible significance of the presence of lymphatic capillaries in the mitral valve is discussed.

Editorial The Importance of the Lymphatics of the Mammalian Heart: Experimental Observations and Some Speculations

THE FACT that mammalian hearts have lymphatics has been known for a long time. Rudbeck1 first mentioned them in 1653. The most recent careful anatomic study was reported in 1939,2 with a considerable number of anatomic studies published during the almost 300 intervening years. In 1940 Drinker and his group3 published their pioneer studies on cardiac lymph obtained in the dog. They believed that the lymphatic system of the heart could have a major role in this organs metabolic economy, even as had been proved for other organs in the body. Nevertheless, to the best of our knowledge, the lymphatic system of the mammalian heart has been almost completely ignored by modern investigators of cardiac physiology and pathology. In 1954 Rusznyak and his co-workers 4 published their pathologic findings in dogs subjected to obstruction of the cardiac lymph outflow, with and without simultaneous occlusion of the coronary venous sinus. Their technic of obstructing cardiac lymph drainage included occlusion of the thoracic duct. In these animals, kept alive up to 2 weeks after surgery, they reported finding cardiac interstitial edema, frequently with visibly di-

The effects of chronic impairment of cardiac lymph flow on myocardial reactions after coronary artery ligation in dogs

Abstract Myocardial changes after an acute coronary arterial occlusion have been studied in two groups of dogs. In one group, obstruction to the cardiac lymphatic drainage had been produced prior to the coronary occlusion. In the second group, no such obstruction to lymph flow was induced. The myocardial changes in the two groups were different, especially with regard to the extent of necrosis, the sequence of inflammatory reactions, and the degree of fibrotic and calcific change. Significantly different also were the reactions in the tissues around the silk used to ligate the coronary artery branch. Characteristically, dogs with obstruction to cardiac lymphatic drainage had increased inflammatory response to the presence of this foreign body; resolution of this inflammatory response was interrupted about 40 days postoperatively by an influx of PMNs. The possible role of obstruction to cardiac lymphatic drainage in predisposing the human heart to infection and inflammation is suggested.

Myocardial pathology after cardiac venous and lymph flow obstruction in the dog

Summary This study, carried out in dogs, was designed to elucidate the effects of cardiac lymphatic and venous obstruction, both separate and combined, on the viability of the myocardium. Specimens were stained with HBFP to demonstrate ischemia. Eleven dogs had venous obstruction, 5 dogs were acute (killed within 24 hours), and 6 dogs were chronic. Sixteen dogs had lymph obstruction, 4 dogs were acute, and 12 dogs were chronic. Twenty dogs had lymph obstruction in addition to venous obstruction, 5 dogs were acute, and 15 dogs were chronic. Nineteen animals served as control animals, 6 dogs were acute, and 13 dogs were chronic. Autopsies excluded all animals with any compromise of the arterial circulation. Large areas of myocardial fibers staining positively with HBFP were seen in acute and chronic experimental dogs from 1 hour to 90 days after operation. No gross or microscopic infarctions were found in the acute or chronic control dogs. Thirty-three per cent of dogs with chronic venous obstruction or chronic lymph obstruction showed gross infarctions without additional microscopic areas of infarction. In dogs with combined venous and lymphatic obstruction, 40 per cent had gross infarctions, whereas 87 per cent had a combination of gross plus microscopically evident infarctions. Thus, interference with the outflow of venous blood and lymph, without interference with the arterial blood supply, can lead to significant myocardial pathology of a type usually associated with a deficit in arterial blood supply. If, as has been postulated, the HBFP stain is specific for ischemic muscle fibers, our results seem to indicate that such a stage of ischemia can persist over a prolonged period of time without progressing to necrosis; or, alternatively, that over the course of time progressively more fibers that are in or near a fibrotic area slowly become ischemic. These findings in dogs provide support for the potential usefulness of myocardial revascularization procedures.

Successful Therapy of Prolonged Hypotension with an Adrenergic Beta-Receptor Blocking Agent

Two patients with prolonged hypotension requiring continuous vasopressor therapy are described.In both patients treatment with nethalide, a beta-receptor blocking agent, appeared clinically effective in allowing the withdrawal of metaraminol therapy and the maintenance of normotension. The results in these patientstend to fortify a hypothesis of peripheral adrenergic beta-receptor dominance in patients with prolonged hypotension.