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Such an action was considered but rejected by Christensenand MacLeod (1945), who did not suppose that plasminwas normally present in the blood.

(3) The spontaneous fibrinolytic activity observedin our subjects is due to an increase in plasmin, and also,apparently, to a decrease in antiplasmin, an observationthat requires further confirmation and investigation.The mechanism by which plasminogen is activated inthese subjects is at present unknown.The foregoing conclusions can be illustrated dia-

grammatically (see figure). Such a scheme, it is realised,is hypothetical, and further work may require funda-

mental alterations.

Our thanks are due to Dr. E. S. Duthie, of the Lister Institute,Elstree, for much advice and practical help, and to Dr. A. tl. T.Robb-Smith for his encouragement and criticism. Thegeneral investigation of fibrinolysis is financed by the MedicalResearch Council.

REFERENCES

Christensen, L. R. (1944) J. Bact. 47, 65.— (1945) J. gen. Physiol. 28, 363.— MacLeod, C. M. (1945) Ibid, p. 559.

Dale, H. H., Walpole, G. S. (1916) Biochem. J. 10, 331.Dastre, A. (1893) Arch. Physiol. 5, 661.Delezene, C., Pozerski, E. (1903) C.R. Soc. Biol. Paris, 55, 327,

690, 693.Glenny, A. T., Barr, M. (1932) J. Path. Bact. 35, 91.Hussey, R. G., Northrop, J. H. (1923) J. gen. Physiol. 5, 335.Jobling, J. W., Peterson, W. (1914) J. exp. Med. 19, 459, 481.Kaplan, M. H. (1944) Proc. Soc. exp. Biol., N.Y. 57, 40.Macfarlane, R. G. (1937) Lancet, i, 10.Milstone, H. (1941) J. Immunol. 42, 109.Nolf, P. (1905) Arch. int. Physiol. 3, 1.

— (1908) Ibid, 6, 306.— (1921) Ibid, 16, 374 ; 18, 549.— (1922) Ibid, 19, 227.

Opie, E. L., Barker, B. I. (1907) J. exp. Med. 9, 207.Tagnon, H. J., Davidson, C. S., Taylor, F. H. L. (1942) J. clin.

Invest. 21, 525, 533.— Levenson, S. M., Davidson, C. S., Taylor, F. H. L. (1946)Amer. J. med. Sci. 211, 88.

Teale, F. H., Bach, E. (1919) Proc. R. Soc. Med. 13 (path.), 4, 43.Yudin, S. S. (1936) Pr. méd. 44, 68.

EXERCISE AND CARDIAC HYPERTROPHY*

Sir ADOLPHE ABRAHAMSO.B.E., M.D. Camb., F.R.C.P.

PHYSICIAN TO WESTMINSTER HOSPITAL AND TO THE INTER-

NATIONAL ATHLETIC BOARD ; HONORARY MEDICAL OFFICERTO THE BRITISH OLYMPIC ATHLETIC TEAM

PHYSICIANS and physiologists differ in opinion on thesubject of cardiac hypertrophy in response to exertion.On the one hand, there is the a priori expectation, theanalogy of the musculature of the blacksmith’s arm.On the other hand, there is the pronouncement of cardio-logists that, provided the cardiac muscle is healthy andthere is no valvular disease, hypertrophy does not developeven after the most severe physical exertion of which ahuman being is capable, whether that exertion bea repetition of occasions of supreme intensity or a

long-continued submaximal effort : hypertrophy - isregarded as evidence or proof of some pathologicalcondition in the cardiovascular system or in some

other system with cardiovascular repercussions. Thoughthe present communication is intended as a criticismwhich may be at variance with previous experi-ence and admit some vacillation iri the retention of along-established opinion, I have on clinical and radio-graphical grounds never found occasion to doubt that thehealthy heart never hypertrophies, and this belief isfounded on very considerable experience of athletes ofevery variety : of oarsmen ; of runners at all distances,from sprinters to Marathon performers ; of cyclistsengaged in such feats as twenty-four hours’ continuouspedalling ; and of Channel swimmers.Analogy with the blacksmith’s arm may well be fal-

lacious ; cardiac muscle is not the same thing as voluntaryskeletal muscle. Moreover, I have always felt thatundue emphasis is laid on the function of the heart in

* A communication to the Association of Physicians, April, 1946.

considering the capacity for athletic distinction and

regarding it as the limiting factor for endurance.

Admittedly the work done by the heart in extremeexertion is of a very high order : each ventricle at maxi-mal pressure delivers thirty-four litres of blood a minute.But, though the argument is specious, it seems to me agratuitous assumption that, granted a peculiarly super.lative circulation ensuring an unlimited provision ofblood, a corresponding delay or avoidance of fatiguewould result. The capacity for physical effort dependson various circumstances. It may well be that the super-athlete owes his capability to the quality of his blood; toits viscosity, perhaps, or even to some subtle biochemicalfactor. It may be that his muscles have exceptionalendowments for oxygen utilisation, for tolerance for lacticacid, or for the development of antibodies to ensure itsneutralisation. Above all there is the nervous element,not only as a coordinating agent for the most perfectharmonisation of all the factors concerned but also fromthe psychological aspect. ,

Comparison with the lower animals is unconvincing.We may measure such details as stroke volume, circula-tion-rate, vital capacity, and oxygen debt. What areimmeasurable and imponderable are such qualities as

determination, stoicism, the ability to withstand dis-comfort and fatigue, or to endure the miseries of heat,cold, hunger, and thirst, and most of all in respect to long-continued exertion, monotony and boredom. The limitingfactors of endurance are by no means restricted to thecirculation.

AN ILLUSTRATIVE CASE

A man, aged 78, consulted Mr. G. T. Mullally for a swellingof the neck of three months’ duration. His previous health-had been consistently excellent; his activity until the lastfew weeks of his life had remained unimpaired. A tumour(probably malignant) of the thyroid gland compressing theoesophagus and invading the right external jugular vein wasdiagnosed, and deep X-ray therapy was undertaken. Suddendeath took place shortly after the start of treatment.As a necropsy was permitted, I requested particular atten-

tion to the heart and blood-vessels. I had not known thedeceased in life, but his reputation as an athlete in his youthwas of an almost legendary order. In the opinion ofauthorities he was the greatest long-distance cyclist of anygeneration. At the age of 18 he broke records for the bicycleand tricycle rides from Land’s End to John o’Groats. Duringeleven vears of incessant cycling he created nineteennational records. He had a partiality for the Land’s Endto John o’Groats achievement, and contemporary membersof our profession warned him that every such performancereduced his life expectation by ten years. This effort he

accomplished on twenty-four occasions.After terminating his career as a long-distance cyclist he

continued as an outstanding performer at cricket, hockey,swimming, and lawn tennis for the remainder of his life. Asa professional soldier he took part in the 1914-18 war (lieut.-colonel and D.s.o.) and in the 1939-45 war with full dutiesin the Home Guard. I regret that no clinical details--e.g.,cardiac rate and blood-pressure—are forthcoming. His

height was 5 ft. 11 in., and his weight, which remained sub-stantially unaltered throughout adult life, was just under 11 st.He was a non-smoker and almost a total abstainer from alcohol.At the necropsy an embolus-the cause of death-was found

in the left pulmonary artery.The lungs were healthy and free from emphysema ; there

was adherence of the left pleura, with a calcified nodule atthe left base. The heart was large, weighing 18 oz., but was" remarkably healthy for a man of his age." The muscle wasfirm and without fatty changes or infarctions. The coronaryvessels were entirely free of atheroma. The aorta was in aremarkable state of health. The valves were normal ; theaortic valves appeared larger than normal, measuring4 cm. x 2 cm."The kidneys were quite normal, weight rt. 6 oz., It. 8 oz.

Liver, spleen (weight 4 oz.), and other viscera were quitenormal." "

DISCUSSION

Here is an example of a man who indulged in themost severe form of violent exercise in his youth

566

for eleven years and in moderately strenuous exertionfor the rest of his life ; who survived with perfect healthto the age of 78 to succumb to malignant growth of thethyroid and a fortuitous pulmonary embolus ; at whosedeath a considerably hypertrophied heart was discovered,with complete absence of any disease in the cardio-vascular system and a condition of exceptional healthinessof all viscera for a man of his age.

It is generally accepted that species or even breeds ofanimals distinguished for muscular power have unusually

large hearts. The ratio heart weight X 100 always

body-weightgreater than 0.6 in those capable of severe continuedexercise. The qualification continued must be stipulated,since animals with very small hearts are capable ofextreme exertion for a short time if no considerableoxygen debt is incurred.But this is not to presume that hypertrophy of the

heart can be induced by severe exercise, and clinicaland radiological investigations applied to athletes whoindulge in long-distance events have provided littleevidence of such effect. Admittedly, these investiga-tions, however skilfully performed, are not conclusive.The only proof is that afforded by necropsy, and appro-priate opportunities are exceptionally rare. Necropsies

of subjects aged 78 are only too likely to reveal degenera-tive changes which are the usual consequence of age.The factors of inactivity, gluttony, and intemperanceall have a bearing ; hence the responsibility of physicalexertion in earlier life can rarely be incriminated as anisolated factor.

I venture to advance two provocative alternativesas a lesson from this example. Either cardiac hyper-trophy, analogous to muscular hypertrophy generally,does develop in response to violent exercise ; or some

human beings naturally possess exceptionally large heartsand are constitutionally fitted for protracted exertion.

SUMMARY

An example is presented of a phenomenal athlete,who died at the age of 78, in whom at necropsy con-siderable hypertrophy of the heart was revealed, butwhose cardiovascular system was in an extremely healthystate.The relationship of cardiac hypertrophy to physical

exertion is discussed.

I am greatly indebted to Mr. G. T. Mullally for permissionto record this note, and to Prof. R. J. V. Pulvertaft forhis generous cooperation in respect to the necropsy andinformation relating to the crucial details.

Reviews of Books

Atlas of Surgical Approaches to Bones and JointsTOUFICK NICOLA, M.D., F.A.C.S., professor of orthopedics,New York Polyclinic. London : Macmillan. Pp. 218.25s.

BY over 200 diagrams and black-and-white drawings,Professor Nicola cleverly and clearly represents themethods of approach to all bones and joints. The chieffeatures are the large scale of the illustrations-almostlife size-and the bold delineation of the structures.Here are no detailed anatomical drawings in the da Vincistyle, nor loose impressionist effects, but bold, semi-diagrammatic drawings which certainly get their messageacross. The approaches are those that Nicola has foundof value, and as such should be good enough for mostof us. The majority are familiar, but some-such as thedeltoid-displacing methods for the shoulder-joint-should be used more often. There are definite advantagesin exposing the lumbar spinal cord with the patient inthe lateral position, as he describes. For the young,this is a simple textbook of the essentials of orthopaedicanatomy, for the old a quick reference work for usebefore a less familiar operation on bone or joint.

Carbohydrate MetabolismSAMUEL SOSKIN, director of the research institute,Michael ReeseHospita), Chicago ; and RACuMiEL LEVINE,director of metabolic and endocrine research at the

hospital. London : Cambridge University Press. Pp. 315.33s.

Claude Bernard’s genius is emphasised in this book.The authors return again and again to the views of thegreat pioneer, upon whose work so much of our know-ledge of carbohydrate metabolism is based. And in thisthe authors show their own greatness, for they setout to provide a book to be used for teaching, bringingthe subject matter up to date, and presenting it suitablyfor the scientifically minded physician. Well designedand critically and sympathetically written, the bookcould only have been put together by men who hadthemselves thought and worked for many years at thesubject. The diagrams and structural formulae are

helpful, and the summary, in the biochemical section,of the enzymatic processes involved in carbohydrateoxidation is very clear. The section criticising theclassical criteria of diabetes is interesting, the authorspiling up the evidence against the non-utilisation theoryin an instructive manner. The role of the endocrineglands in carbohydrate metabolism is fully discussed,and with surprising simplicity. Some of the final chapterswill appeal most to clinicians. Some aspects of carbo-

,/

hydrate metabolism which have been almost neglectedmight with advantage have been included. The referencestó, and accounts of, the pentose sugars for instanceare incomplete enough to be misleading, and there islittle description of our growing knowledge of the sugarsconcerned in nucleic acid metabolism ; but perhapsthese subjects hardly came within their terms ofreference.

Symptomatic Diagnosis and Treatment of Gynaeco-logical Disorders

(2nd ed.) MARGARET MOORE WniTE, M.D., F.R.C.S.,lILR.C.O.G., surgical specialist, Three Counties Emer-

gency Hospital. London : H. K. Lewis. Pp. 246.16s.

THIS small book, published in the " General Prac-titioner ’’ series, covers a wide territory and covers itwell. The subject matter is up to date ; the diagnosisand treatment are sound, and the illustrations graphic.Miss Moore White counsels expectant treatment inintratubal pregnancy with death of the foetus, and inabortion of a separated tubal pregnancy. This may besafe for a surgeon of her diagnostic acumen and wideexperience, but in writing for general practitioners suchadvice seems dangerous, since the extra-uterine pregnancywhich is likely to bleed and the one which is not mayeasily be confused, with disastrous results for the patient.The chapter on sterility is among the best in any textbookof gynaecology, and a useful chapter on contraceptionhas been contributed by Dr. Mary Redding. Irradiationtherapy is discussed by Mr. 1. G. Williams, who adequatelycovers the needs of general practice.

A Textbook of Surgery(4th ed.) Editor : FREDERICK CHRISTOPHER, M.D., F.A.C.S.,associate professor of surgery, Northwestern Univer-sity, Chicago. London: W. B. Saunders. Pp. lo48.50s. °

THIS new edition has been revised and reset, and twonew sections have been added on chemotherapy andmilitary surgery. New readers may or may not dislikethe double-column page ; and there is some inevitableunevenness associated with the multiplicity of authors,so that the sections on the operative treatment oftrigeminal neuralgia or spina bifida are as long as thewhole section on tuberculosis of joints. But these areminor criticisms. The illustrations are everywheregood, particularly those of operative procedures, andthe style is generally lucid and fluent. This book hasalways been among the transatlantic productions whichBritish undergraduates could read with profit and pleasure,and they will find it a useful adjunct to our own standardworks.