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MECHANISM OF HEART-FAILURE
1029
specimens, and the types of micro-organism The species available, divided into lists of alg’se and protozoa, bacteria, fungi, yeasts, viruses, and bacteriophages, follow the directory. In the Canadian publication there are separate lists for each laboratory ;s
cultures
or
maintained.
in the U.K. and New Zealand lists code numbers are used opposite each species name, and it is a matter of some interest to the permanent committee to learn which arrangement is found the more useful. The United Kingdom and New Zealand directories, both printed in England, show all the signs of austerity, and in lay-out compare unfavourably with the Medical Research Council’s memorandum no. 21-the list of species maintained in the National Collection of Type Cultures, which has
reached its third edition. The Canadian directory, printed by a photographic offset process, is a much larger volume in a handsome loose-leaf binder. These lists are not intended to be catalogues and do not give details of individual strains, but they serve a useful purpose in showing where strains of a species are The nomenclature used is simple, and to be found. common synonyms are shown.. Mycologists may complain that the authority for names is not given, but such an elaboration would have unduly increased the cost of each publication. now
MEDIASTINAL TUBERCULOMA IN applying the term " tuberculoma " to tuberculous processes in the chest it should be remembered that the word implies a clinical and radiological entity, and not a pathological one. The commonest tuberculous masses in the mediastinum consist of enlarged hilar glands ; but clearly it would be misleading to include the glandular element of a primary focus under the heading of tuberculoma. Storey and Lyons1 have lately described 6 cases of mediastinal ’’ tuberculomata "-that is, of mediastinal shadows, discovered radiologically, which after operation and histological examination were found to have a tuberculous origin. They suggest that the lesions were not tuberculous lymphadenitis, for they were isolated and mostly confined to an area in the junction between the azygos vein and the superior vena cava, and no trace of lymphatic tissue could be found in them. But, though the distribution of hilar glands is by no means constant, the chain which runs from below the azygos vein to the base of the neck along the posterior border of the superior vena cava commonly contains a gland in the very area described as the common origin of these " tuberculomata." Thus it seems that stronger evidence is needed before these lesions are classified separately from tuberculous lymphadenitis. Another question raised by this paper is how often, if ever, these tuberculous lesions should be resected. Storey and Lyons think that one of the chief indications for exploration is doubt as to the nature of the tumour. There remains the problem of whether the glandular element of a primary focus should ever be removed. With involvement of isolated paratracheal glands it may sometimes be possible to eradicate surgically the tuberculous process and so to eliminate the possibility of reactivation or of miliary tuberculosis and meningitis due to rupture of the focus into the superior vena cava. In other patients in whom the glands are causing persistent pulmonary collapse, with the probability of permanent damage, early removal of these and, if necessary, the affected pulmonary tissue2 may be possible. Thus, treatment of tuberculous glands of the mediastimust in the great majority of cases remain conservative, thoracotomy may be justified in an increasing
though num ,
proportion. 1. Storey, C. F., Lyons, W. A. Proc. Mayo Clin. 1951, 26, 381. 2. Thomas, D. M. E. Personal communication.
MECHANISM OF HEART-FAILURE of myocardial failure is hardly less of a mystery than it was centuries ago when, by good fortune or trial and error, the condition was found to improvee with administration of digitalis, squills, or extract of toad skin. There is new hope, however, that fundamental research into the mechanism of muscular contraction, together with pharmacology and clinical experience, will throw some light on the subject. Congestive failure is commonly associated with tachycardia, and perhaps ageing heart-muscle cannot restore with normal rapidity the potential energy dissipated in contraction. A tentative explanation of this inability has been given by Dr. A. Szent-Gyorgyi, who is well known for his work on voluntary muscle. There is no reason to suppose that voluntary and cardiac A muscle-fibre muscle are fundamentally different. contains various proteins, of which myosin and actin In seem to be particularly important for contraction. the relaxed state the proteins are long threads. When the muscle is stimulated they contract, with a latency of only 3 milliseconds, and become shorter, thicker, and perhaps coiled, like springs released from tension. At the New York Academv of Medicine on Oct. 28, Dr. Szent-Gyorgyi that negative charges on the myosin molecules are balanced by an outer layer of positive charges due to potassium. Thus neighbouring myosin fibres, with like surface charges, repel each other and are kept in a stretched form and in solution. If the positive potassium charge is wholly neutralised the fibres, following the law of colloid behaviour, approach, adhere, and flocculate or contract ; actin is important in facilitating the flocculation. It is already known that ionic movements and changes of potential are initiated by the arrival of a stimulus. When muscle relaxes, its potential energy and ionic balance is restored from energy released by the disruption of adenosine-triphosphate ; and energy for resynthesis of this is provided by breakdown of carbohydrate. In Szent-Gyorgyi’s hypothesis the emphasis is on ionic balance. At rest, he points out, potassium is held in the muscle cells. During contraction the cells become permeable, and some of the potassium moves outside. Actomyosin contracts best at an ionic balance found soon after a beat. If contraction is repeated too quickly insufficient potassium will have returned to the cells ; if contraction is delayed the concentration will be excessive. Following a period of rest the optimal concentration occurs only after several beats. Here is a possible explanation of the staircase phenomenon familiar to medical students working on frog hearts in the physiology laboratory. Szent-Gyorgyi and his colleagues have also found that blood-serum contains a sterol substance which prevents the staircase phenomenon by making the cell membrane less permeable to re-entry of potassium ; and deoxycortone, the cardiac glycosides/ and, to a small extent, progesterone have the same action. Deoxycortone and the active glycosides have in common the unsaturated lactone ring thought to be essential for cardiac action. Szent-Gyorgyi suggests that in congestive failure a disorder of potassium metabolism causes an imbalance of these ions in the muscle. A failing heart may quicken because only thus can it maintain a favourable potassium balance. Quickening, however, shortens the recovery period ; and digitalis may be benencial because, by decreasing the re-entry of potassium into the cells, it permits a slower beat and therefore better recovery. This interesting hypothesis may or may not prove correct, but it is a good example of the way in which fundamental research can make for rational medicine. But let us not forget that however rational therapy may become, the patient still needs faith. THE
cause
suggested
1. Cattell, J. M.
Fed. Proc. 1943, 2, 76.
specimens, and the types of micro-organism The species available, divided into lists of alg’se and protozoa, bacteria, fungi, yeasts, viruses, and bacteriophages, follow the directory. In the Canadian publication there are separate lists for each laboratory ;s
cultures
or
maintained.
in the U.K. and New Zealand lists code numbers are used opposite each species name, and it is a matter of some interest to the permanent committee to learn which arrangement is found the more useful. The United Kingdom and New Zealand directories, both printed in England, show all the signs of austerity, and in lay-out compare unfavourably with the Medical Research Council’s memorandum no. 21-the list of species maintained in the National Collection of Type Cultures, which has
reached its third edition. The Canadian directory, printed by a photographic offset process, is a much larger volume in a handsome loose-leaf binder. These lists are not intended to be catalogues and do not give details of individual strains, but they serve a useful purpose in showing where strains of a species are The nomenclature used is simple, and to be found. common synonyms are shown.. Mycologists may complain that the authority for names is not given, but such an elaboration would have unduly increased the cost of each publication. now
MEDIASTINAL TUBERCULOMA IN applying the term " tuberculoma " to tuberculous processes in the chest it should be remembered that the word implies a clinical and radiological entity, and not a pathological one. The commonest tuberculous masses in the mediastinum consist of enlarged hilar glands ; but clearly it would be misleading to include the glandular element of a primary focus under the heading of tuberculoma. Storey and Lyons1 have lately described 6 cases of mediastinal ’’ tuberculomata "-that is, of mediastinal shadows, discovered radiologically, which after operation and histological examination were found to have a tuberculous origin. They suggest that the lesions were not tuberculous lymphadenitis, for they were isolated and mostly confined to an area in the junction between the azygos vein and the superior vena cava, and no trace of lymphatic tissue could be found in them. But, though the distribution of hilar glands is by no means constant, the chain which runs from below the azygos vein to the base of the neck along the posterior border of the superior vena cava commonly contains a gland in the very area described as the common origin of these " tuberculomata." Thus it seems that stronger evidence is needed before these lesions are classified separately from tuberculous lymphadenitis. Another question raised by this paper is how often, if ever, these tuberculous lesions should be resected. Storey and Lyons think that one of the chief indications for exploration is doubt as to the nature of the tumour. There remains the problem of whether the glandular element of a primary focus should ever be removed. With involvement of isolated paratracheal glands it may sometimes be possible to eradicate surgically the tuberculous process and so to eliminate the possibility of reactivation or of miliary tuberculosis and meningitis due to rupture of the focus into the superior vena cava. In other patients in whom the glands are causing persistent pulmonary collapse, with the probability of permanent damage, early removal of these and, if necessary, the affected pulmonary tissue2 may be possible. Thus, treatment of tuberculous glands of the mediastimust in the great majority of cases remain conservative, thoracotomy may be justified in an increasing
though num ,
proportion. 1. Storey, C. F., Lyons, W. A. Proc. Mayo Clin. 1951, 26, 381. 2. Thomas, D. M. E. Personal communication.
MECHANISM OF HEART-FAILURE of myocardial failure is hardly less of a mystery than it was centuries ago when, by good fortune or trial and error, the condition was found to improvee with administration of digitalis, squills, or extract of toad skin. There is new hope, however, that fundamental research into the mechanism of muscular contraction, together with pharmacology and clinical experience, will throw some light on the subject. Congestive failure is commonly associated with tachycardia, and perhaps ageing heart-muscle cannot restore with normal rapidity the potential energy dissipated in contraction. A tentative explanation of this inability has been given by Dr. A. Szent-Gyorgyi, who is well known for his work on voluntary muscle. There is no reason to suppose that voluntary and cardiac A muscle-fibre muscle are fundamentally different. contains various proteins, of which myosin and actin In seem to be particularly important for contraction. the relaxed state the proteins are long threads. When the muscle is stimulated they contract, with a latency of only 3 milliseconds, and become shorter, thicker, and perhaps coiled, like springs released from tension. At the New York Academv of Medicine on Oct. 28, Dr. Szent-Gyorgyi that negative charges on the myosin molecules are balanced by an outer layer of positive charges due to potassium. Thus neighbouring myosin fibres, with like surface charges, repel each other and are kept in a stretched form and in solution. If the positive potassium charge is wholly neutralised the fibres, following the law of colloid behaviour, approach, adhere, and flocculate or contract ; actin is important in facilitating the flocculation. It is already known that ionic movements and changes of potential are initiated by the arrival of a stimulus. When muscle relaxes, its potential energy and ionic balance is restored from energy released by the disruption of adenosine-triphosphate ; and energy for resynthesis of this is provided by breakdown of carbohydrate. In Szent-Gyorgyi’s hypothesis the emphasis is on ionic balance. At rest, he points out, potassium is held in the muscle cells. During contraction the cells become permeable, and some of the potassium moves outside. Actomyosin contracts best at an ionic balance found soon after a beat. If contraction is repeated too quickly insufficient potassium will have returned to the cells ; if contraction is delayed the concentration will be excessive. Following a period of rest the optimal concentration occurs only after several beats. Here is a possible explanation of the staircase phenomenon familiar to medical students working on frog hearts in the physiology laboratory. Szent-Gyorgyi and his colleagues have also found that blood-serum contains a sterol substance which prevents the staircase phenomenon by making the cell membrane less permeable to re-entry of potassium ; and deoxycortone, the cardiac glycosides/ and, to a small extent, progesterone have the same action. Deoxycortone and the active glycosides have in common the unsaturated lactone ring thought to be essential for cardiac action. Szent-Gyorgyi suggests that in congestive failure a disorder of potassium metabolism causes an imbalance of these ions in the muscle. A failing heart may quicken because only thus can it maintain a favourable potassium balance. Quickening, however, shortens the recovery period ; and digitalis may be benencial because, by decreasing the re-entry of potassium into the cells, it permits a slower beat and therefore better recovery. This interesting hypothesis may or may not prove correct, but it is a good example of the way in which fundamental research can make for rational medicine. But let us not forget that however rational therapy may become, the patient still needs faith. THE
cause
suggested
1. Cattell, J. M.
Fed. Proc. 1943, 2, 76.