CENTRAL VENOUS PRESSURE AND BLOOD-VOLUME

701 DISAPPEARANCE-RATE OF EXOGENOUS HUMAN INSULIN SIR.—In the course of current studies of human forearm metabolism, we have observed that the half-life of insulin after its injection is much shorter than has been previously accepted. We have followed the decrease in serum-insulin concentrations in arterial and venous blood at 3-minute intervals after injection of exogenous human insulin (Novo). In the left-hand side of the accompanying figure, which ;hows results from one experiment, immunological insulin concentrations1 are plotted on a logarithmic scale on the

Arterial (+) and venous (0) insulin concentrations: on units of human insulin, with fasting values shown as subtraction of fasting values.

I am entirely in agreement with your exhortation, but do let it be remembered that money, apparatus, and enthusiasm are not enough. Skilled assistance is needed when a researchminded consultant is, by choice, working full-time with a limited staff. Technicians are everywhere scarce, but the teaching hospitals with their prestige appeal and additional sources of revenue inevitably win. For the most part bronchitic patients attend peripheral hospitals where assistant staff of registrar grade, able to do investigative work, may be difficult to find, and indeed, given the ability, the routine work-load may be too great to permit of investigative work such as you suggest and I have undertaken. The enthusiastic consultant will be unwilling to remain only a doer of routine physiological studies, and will inevitably enlarge his interests; this in turn will undoubtedly involve radiological and pathological studies. His colleagues may not be interested in this aspect of their discipline, and even if interested may be unable to devote time to it. Without technical help and colleague support, in addition to other frustrations such as hospital rebuilding and staff recruitleft-hand side, after injection of 8 ments, he may feel that the effort is a and v; on right-hand side, after not worth while and give up, or even

ordinate, against time. The venous concentrations are seen ro be higher than the arterial ones throughout the fall; the half-life is 11 minutes on the two curves. The time-difference between identical values is about 3 minutes, but this does not permit the calculation of an exact mean transit-time in this forearm. It is probable that the production of endogenous insulin is reduced during such an experiment, but we do not know to what extent. Assuming that pancreatic output of insulin does not change at all, one can obtain a half-life for injected insulin by subtracting the fasting values. This is done in the righthand side of the accompanying figure, and permits the calculation of a half-life of 71/2 minutes. Accordingly the true value must be between 711z and 11 minutes. In 5 patients investigated in this way, insulin half-lives were between 5 and 15 minutes. Time of distribution was about 20 minutes, and the space of distribution was about 20% of body-weight, when the arterial curves were used for calculation. There is evidence that the breakdown of endogenous insulin is of the same order of magnitude.2 These values are evidently shorter than those reported by Berson et a1.,3 who followed the litilisation of 131T-beef- insulin. Izzo et al.4 and Arquilla et al.5 have pointed out, however, that the rate of biological breakdown of insulin depends on the degree of iodination. 2nd University Clinic of Internal Medicine, Arhus General Hospital, Arhus, Denmark.

HANS ØRSKOV NIELS JUEL CHRISTENSEN.

ASSESSMENT OF LUNG FUNCTION SIR,—I should like to comment on the wider implications of

leading article (Sept. 10, p. 577). plunge that you recommend many years ago and water invigorating, but it has gradually got colder the

I took the

1 Hales, C. N., Randle, P. J. Biochem. J. 1963, 88, 137. E., Marks, V. Lancet, Sept. 24, 1966, p. 700. 3 Berson, S. A., Yalow, R. S., Barman, A., Rothschild, M. A., Newerly, K J clin Invest. 1956, 35, 170. 4 J L, Roncone, A., Izzo, M. J., Bale, W. F. Excerpta med. no. 74, p 44 (abstract). 5 lla, E R, Ooms, H., Finn, J. Diabetologia, 1966, 2, 1.

2 Samols,

and the current has proved faster than I had anticipated. I found it difficult to get others to join me in the aquatic exercise, and I am now drying myself on the bank.

worse may be lured away by the financial attractions of part-time work. I think that, for the future development of a healthy hospital service, he should be encouraged in every way. Why not allow him sabbatical leave to recharge his batteries ? I feel therefore that it will need a radical change of medical climate before the enthusiastic consultant can be encouraged to take the plunge, and to find the water warm and invigorating, and the current favourable. Time is not on our side. Chase Farm Hospital, T. SIMPSON. Enfield, Middlesex.

CENTRAL VENOUS PRESSURE AND BLOOD-VOLUME Friedman and his colleagues assert, last week SIR,-Dr. that " there is (p. 609), general agreement " that a raised central

(c.v.P.) signifies heart failure, and that increase in blood-volume increases venous return. But C.v.P. rises in normal people during exercise. In 19641I explained why this happens and why it is physiologically necessary. I also showed why venous return is independent of blood-volume and of hxmorrhage or transfusion. A simple analogy will best illustrate my points. The vascular bed is in essence an inflatable, elastic container (like a rubber bladder) with inlet and outlet joined by a passively filling pump. Leaving aside the indirect effect on pump filling pressure, it is surely obvious that the amount circulated is independent of the volume contained by the distensible bladder, or of volumes added to or subtracted from it. These simply inflate or deflate the balloon. Only its internal pressure can affect circulation-rate, and this is dependent upon " tone in its wall as well as upon its overall state of distension. It is not " venous return " (an unhelpful concept) but venous pressure which influences cardiac output, for only pressure can alter diastolic filling. Venous return is virtually the same as cardiac output, since only alterations in the proportions of blood in the systemic and pulmonary circuits can affect venous

repeat the old

1.

pressure

fallacy

Johnson, H. D. Br. J. Surg. 1964, 51, 276.

702 them differently. Moreover these can form only a tiny proportion of the total volume circulating in a period of a few minutes. Department of

Experimental Surgery, Postgraduate Medical School, Ducane Road, London W.12

H. DAINTREE

JOHNSON.

after eating fat-containing " modified American-style muffins no more than that. Certainly one cannot reasonably infer fr::- ! such evidence that, when the dyspeptics previously complained of indigestion induced by, say, Australian-style roast beef and Yorkshire pudding, bacon and eggs, or fried fish and chips their symptoms were " more likely related to prejudice about fat, or domestic or personal disturbances at the time of eating Fat, sir, is one thing. Food cooked in fat is another. D. M. DAVIES "

-

SIR,-The interesting article on central venous pressure (c.v.p.) and direct serial isotope-dilution measurements of bloodvolume by Dr. Friedman and his colleagues needs careful reading if confusion is to be avoided. The use of the Volemetron ’, a device for computing the isotope dilution, is certainly a very useful guide to volume correction in conjunction with the intelligent use of c.v.p. estimation, especially in cases of long-established shock treated by noradrenaline. It would be a pity, however, if this were taken to mean that the volemetron measurement is generally more useful or reliable than, or in any way a substitute for, the cheaper and universally available c.v.p. estimation; it would be a tragedy if it were thought that ‘

either or both these values were of any significance at all except as part of the clinical picture as a whole. Measurement of c.v.p. is but a more convenient and accurate way of using that valuable clinical sign, the jugular venous pressure. It should in no way be confused with venous return. Experience of many hundreds of patients, particularly after cardiac surgery, when cardiac capability, circulating volume, and the state of the circulatory pathways are notoriously unstable, has shown that measurement of c.v.p., as an integral part of the clinical picture, is an invaluable method in preventing hypovolasmia. In these circumstances the volemetron, while of great interest, has not been so useful in practice; indeed, measured replacement to a theoretical normal volume would often prove grossly inadequate. c.v.p. is particularly useful in conjunction with other clinical signs, because it gives an indication of the filling of the circulatory system, at that moment in time, relative to cardiac function. Next in usefulness would come measurement of blood gases, especially central venous oxygen, as an indication of the function of the circulation. c.v.p. does not in any way indicate whether the circulating blood-volume is normal. Department of Surgery, Postgraduate Medical School, A. H. B. DE BONO. Ducane Road, London W.12.

DESIPRAMINE AND HYPERTENSIVE EPISODES SIR,-Dr. Murray and Dr. Smith suggest (Sept. 10, p. 591) that the patient described in my letter (Aug. 20, p. 436) had hypercapnia. This patient received artificial ventilation throughout the operation from a ’Cyclator ’ ventilator with a Beaver non-rebreathing valve. The minute-volume was maintained at around 10 litres. Assuming that the patient’s metabolic rate was 85% of basal, this would give an arterial carbon-dioxide tension between 15 and 20 mm. Hg. There was no reason at the time to suspect that the patient was inadequately ventilated, and it is most unlikely that she had was vaporised in a Boyle’s bottle and the anaesthetic mixture then passed into the ventilator, where it was of course diluted by the driving gas (oxygen). The final concentration was in the region of 1 %. Trichloroethylene could only cause hypercapnia under these conditions by altering the solubility of carbon dioxide, but I know of no evidence to suggest that this happens.

hypercapnia. Trichloroethylene

of Anæsthetics, Addenbrooke’s Hospital,

Department

Trumpington Street, Cambridge.

J. V. FARMAN.

FATTY FOODS AND DYSPEPSIA SIR,—While admiring the industry and ingenuity of Miss Taggart and Dr. Billington in their investigation of the relationship between fatty foods and dyspepsia (Aug. 27, p. 464), one must question their interpretation of results. They have shown by their elegant culinary manipulations only that in most cases their patients did not suffer dyspepsia

GOITROGENIC EFFECT OF WALNUTS SIR The interesting letter from Dr. Linazasoro and othe: (Aug. 27, p. 501) makes me wonder whether the goitrogen,; effect produced by walnuts could be mediated via seroton: (5-hydroxytryptamine). Walnuts contain a high concentration of serotonin,! and moreover reserpine (a potent liberator o: biogenic amines) in a concentration of 0-083 mg. per ml. bas been shown to reduce the uptake of 1311 by calf-thyroid slices. Department

of

Pharmacology,

School of Medicine, Los Angeles, California 90024.

JEREMY H. THOMPSON.

WHO WILL VACCINATE THE VACCINATORS? SIR,-I was greatly interested in your leader last week (p. 627) on a matter which has long needed emphasising. As the cross-infection officer for the United Cardiff Hospitals I have for some time been disturbed by the lack of knowledge which certain grades of staff have about their immunisation against smallpox and indeed of their overall inoculation state. Is it not time that all workers employed in National Health Service hospitals and other medical institutions were supplied with a standardised personal inoculation-record document which could be carried at all convenient times, as has been the practice in military circles for many years ?Iwould go further than this and suggest that it would be wise policy to ensure that all those of responsible age-e.g., school-leavers-be supplied with such documents, each containing the individual’s immunisation history. I know there are arguments for and against such cards,3 but I feel that such a card is better than none at all. I would also suggest that members of crossinfection committees would perhaps be the obvious people to regularly review and take action on the immunisation statistics of the staff in their hospitals, if this is not already practised. School of Medicine, R. A. HOLMAN. Cardiff.

SIR Your leader last week

was of special relevance of a recent outbreak of variola minor. B ’ mere chance an adult woman, primarily perhaps for noemedical reasons, was admitted with " chickenpox " to a Salford hospital which admits a number of cases of infectious disease. She was ill, prostrate with a rash of typical smallpox distriretion. A child contact was soon found quite ill at home with a similar rash. There had been much interchange of staff patients, and visitors, laundry, and food trolleys in several wards of two large hospitals. The sudden and at first sigh alarming occurrence of smallpox turned out later to be partof: an outbreak of alstrim, which faded out-mainly by sheer good luck-with less than a score of known cases. In the earliest days, over 1500 hospital staff were " at risk , and probably together with some hundreds of known " contacts, apart from the thousands of possibles ". and speedy action appeared essential. The very potent used nowadays produced more than a fair share of rea;::r This led to the partial disablement, at one hospital, of

here

on account

man

1. 2. 3.

Kirberger, E. Biochim. biophys. Acta, 1961, 49, 391. Mayer, S. W., Kelly, F. H., Morton, M. E. J. Pharmac. exp 117, 197. Parish, H. J., Cannon, D. A. Antisera, Toxoids, Vaccines and the culins in Prophylaxis and Treatment; chap. 27. London, 1961