DIET AND MYOCARDIAL METABOLISM

515 of preventing the excess cataract in those areas". There is little doubt that cataract formation is a multifactorial process. There are reasons to suspect that both sunlight exposure and severe dehydrating events may play a role. Studies are needed to determine definitively what, if any, are their contributions to this major cause of blindness. can concentrate on means

International Center for

Epidemiologic and Preventive

ALFRED SOMMER HUGH TAYLOR JAMES TIELSCH SHEILA WEST

Ophthalmology, Dana Center, Wilmer Institute, Johns Hopkins Medical Institutions, Baltimore, Maryland 21205, USA

significantly higher at 1 week than later (see table); no significant changes were found in dihomo-y-linoleic acid (20:3n6). The explanation for these findings is unknown in the absence of concomitant dietary data. In view of the rapid changes in the platelet membrane fatty acids profiles that may occur following alterations in the diet,’ it might be speculated that these early changes reflect acute disturbance in the diet after acute myocardial infarction. However, the Edinburgh workers have observed that subjects who have underlying heart disease but no knowledge of it have a low intake of linoleic acid in the diet (and, as a result, a low tissue level of this fatty acid), whereas those who know that they have heart disease have a high intake. Thus awareness of heart disease seems to lead to increase in P/S ratio in the diet. This would correspond with the rise in platelet linoleic acid and fall in oleic acid that occurred in the post-myocardial-infarction period in our study and indicate that the initial levels of these fatty acids were a reflection of fatty acid status before myocardial infarction. It was not clear from the Scottish study whether the higher levels of linoleic acid in the adipose tissue and diet in the known coronary heart disease group (compared with the group with no heart disease) were statistically significant. If so, it would suggest that personal experience of heart disease provides a powerful stimulus to change in dietary habits. an

1. Minassian DC, Mehra V, Jones BR. Dehydration crisis from heatstroke and risk of cataract. Lancet 1984; i: 751-53.

severe

diarrhoea

or

ADIPOSE TISSUE FATTY ACIDS AND CHD

SIR,-The paper by Professor Oliver and colleagues (July 21, p 117), examining some aspects of the possible role of linoleic acid in causation of coronary heart disease (CHD), is surely a valuable contribution. But perhaps they (at beginning and end of the discussion section) conclude too readily that the lower level of linoleic acid in adipose tissue found in new CHD patients is most likely to be due to lower dietary intake. Before accepting this we must first ask a question and consider other findings: (1) Was the dietary linoleic acid intake 50-60 years ago, and before CHD became common, greater than that of recent years? (2) The strong negative correlation found between number of cigarettes smoked and tissue levels of linoleic acid suggests that metabolic handling plays an important part in determining tissue levels. (3) The low linoleic acid levels found in children with essential fatty acid deficiency are surely of metabolic and not primarily of dietetic origin-again suggesting that dietary intake is not necessarily the main factor in determining tissue levels. So can we really be so sure just which is the horse and which the cart? We cannot lightly dismiss the possibility that, in CHD unfortunate metabolic aberration of thus far candidates, unknown origin itself causes the demonstrated lowering of adipose tissue linoleic acid levels. some

C. D. NEEDHAM

SIR,-The findings of the Edinburgh group have some similarities sequential study of platelet membrane fatty acids following myocardial infarction that we have carried out. 40 patients, previously fit, were studied one week after their first myocardial to a

infarction. 17 controls were also tested. The myocardial infarction group was restudied at one and three months. No special dietary advice was given. Lipids were extracted from platelets with a chloroform/methanol mixture. Fatty acid methylesters were prepared by acid transmethanolysis. The esters were extracted with hexane and analysed by gas chromatography. 18 separate fatty acids were identified in each sample and each peak was quantified as a percentage of the total fatty acids in the sample. On preliminary analysis there were no important differences between control and myocardial infarction groups’ fatty acid profiles. However, within the myocardial infarction group linoleic acid (18:2n6) was significantly lower and oleic acid (18:2n9) was LINOLEIC ACID AND OLEIC ACID CONTENT OF PLATELET MEMBRANE

PHOSPHOLIPIDS

(MASS

% OF TOTAL FATTY

ACIDS) AFTER

MYOCARDIAL INFARCTION AND IN A CONTROL GROUP

I

Results

I

I

expressed mean±standard deviation. Comparison within myocardial infarction group, Kruskal-Wallis test, comparison of myocardial infarction group with controls, - BBann- WhItney LT.tes!. * = p
Addenbrooke’s

Hospital,

C. G. H. MAIDMENT S. P. JONES

Cambridge

University of

East Anglia,

E. J. A. LEA

Norwich

W, Roth P, Scherer B, Kurzmann I, Bohlig B, Weber PC Platelet-membrane fatty acids, platelet aggregation and thromboxane formation during a mackerel diet.

1. Seiss

Lancet 1980; i 441-44

DIET AND MYOCARDIAL METABOLISM

SIR,-Myocardial rate, wall

oxygen demand is

largely determined by heart

tension, and myocardial contractility. It is also influenced

degree by myocardial substrate utilisation: a change from predominantly lipid usage, as in fasting, to carbohydrate utilisation reduces myocardial oxygen consumption. Infusions of glucose/ insulin/potassium (GIK) have been applied to evoke this metabolic shift which reduces the ischaemic injury in experimental canine myocardial infarction. Similar GIK infusions in patients with angina pectoris upon pacing on physical exercise have not,had a clearcut beneficial effect. 2-5 Dr Thuesen and colleagues (July 14, p 59) describe an uncontrolled 3-month experiment on the effects of a low-fat lowcalorie diet on myocardial metabolism in patients with angina pectoris. Their data are interesting and conflicting: pacing time up to angina was prolonged (statistical significance not given) and data on lactate extraction upon pacing indicated attenuated myocardial ischaemia in the repeat study after 3 months on the experimental diet. Yet myocardial free fatty acid utilisation and arterial glucose concentrations did not change (they do not report on myocardial glucose utilisation). This apparent paradox leads to a speculative discussion failing to uncover cause-and-effect relations. An explanation for the reduced myocardial ischaemia in the repeat study may emerge from the study design. They cite the work of Thadani et al6 in showing that atrial pacing is a reproducible means of stressing the heart. That study, as well as the original description of the technique,explored the reproducibility of atrial pacing to cause myocardial ischaemia by successive pacing runs separated by rest periods of only minutes. The reproducibility of the stable high heart rate used by Thuesen et al has not been assessed over a 3-month period, although stepwise increase in pacing rate results in reasonably reproducible rate-pressure products after some months of placebo therapy.s In the absence of an evident metabolic explanation, the finding of reduced myocardial oxygen consumption paralleled by decreased coronary-sinus blood flow at identical rate-pressure products is strongly suggestive of lower myocardial contractility due to less sympathetic drive in the repeat study. Significantly lower heart rate and/or blood pressure at rest in the repeat study (their table II) point in the same direction. The conclusion of Thuesen et al that myocardial metabolism can be favourably altered in patients with angina pectoris by dietary means to some

516 can be accepted only after biochemical demonstration of a relevant shift in myocardial substrate utilisation and after study of contemporaneous controls on an ordinary diet. This would demonstrate or exclude the confounding circulatory effects of anxiety especially inherent in studies with intravascular

manipulations. Department of Medicine, University Central Hospital, First

M. H. FRICK

Helsinki, Finland 1. Maroko PR,

Libby P, Sobel BE, et al. Effect of glucose, insulin, potassium infusion on myocardial infarction following experimental coronary artery occlusion. Circulation 1972, 45: 1160-75.

2 Lesch

M, Teichholz LE, Soeldner JS, Gorlin R. Ineffectiveness of glucose, potassium and insulin infusion during pacing stress in chomc ischemic heart disease. Circulation 1974; 49: 1028-37 3 Chiong MA, West RO, Parker JO. The protective effect of glucose-insulin-potassium on the response to atrial pacing. Circulation 1976; 54: 37-46 4. Kostis JB, George JA, Kiyoshi H, Moreyra AE, Kwo PT. Harmful effect ofglucoseinsulin-potassium on patients with coronary artery disease during exercise stress (abstr). Am J Cardiol 1977; 39: 289. 5. Thadani U, Chiong MA, Parker JO Effects of low and high glucose in a glucoseinsulin-potassium infusion on hemodynamics and exercise tolerance in patients with angina pectoris. Circulation 1980, 61: 266-76. 6. Thadani U, Lewis JR, Mathew TM, West RO, Parker JO. Reproducibility of clinical and hemodynamic parameters during pacing stress testing in patients with angina pectoris. Circulation 1979; 60: 1036-44 7. Sowton GE, Balcon R, Cross D, Frick MH. Measurement of the angina threshold using

atrial pacing. A new technique for the study of angina pectoris Cardiovasc Res 1967; 1: 301-07 8. Frick MH, Somer T. Assessment of the effect

pectoris

by atrial pacing

and

physical

of long-term dipyramidole

exercise.

in angina Ann Clin Res 1971, 3: 143-49.

LOW CIRCULATING VITAMIN K LEVELS AND FRACTURED FEMUR

SIR,-The observations of Dr Hart and others (Aug 4, p 283) add my anxiety about the possible effects of coumarin anticoagulants in patients with fractured neck of femur. On the one hand, we know that 10% of this elderly, high-risk group sustain a fatal pulmonary embolus, and that full-dose anticoagulation with heparin and coumarins offers the only proven way of reducing this risk.1 On the other hand, we know that vitamin to

K is necessary for the provision of the carboxylated glutamate residues which are required to allow calcium to take part in both blood coagulation and in bone calcification. Might the administration of vitamin K antagonists to hip-fracture patients substitute one evil for another, in that their fatal pulmonary emboli are replaced by disabling non-union? Have Hart and colleagues extended their observations to look at the relation between vitamin K levels and fracture outcome, and should additional studies now be initiated on the effect of oral anticoagulants on fracture healing? We may be facing a choice between death and disability, so we urgently need the facts on which we can base our decisions. Department of Medicine, University Hospital, Queen’s Medical Centre, Nottingham NG7 2UH

J. R. A. MITCHELL

GK, Mitchell JRA. Clinical management of venous thrombo-embolism. Med Bull 1978; 34: 169-75

1. Morris

Br

ENTEROHEPATIC CIRCULATION OF VITAMIN D p 1376) have ratsi and man2,3 that significant previous amounts of orally or parenterally administered vitamin D are excreted in bile, mainly as polar metabolites, and that only very small amounts of free vitamin D or 25-hydroxyvitamin D (25-OHD)

SIR,-Dr Clements and colleagues (June 23,

confirmed

are

reports in

present in bile, either before

&bgr;-glucuronidase. We

have

or

mean cumulative 24 h T-tube biliary radioactivity excretion that we demonstrated (6. 7% of administered dose) is very similar to the values obtained by Clements et al (7 - 507o and 6 - 5% of the oral and intravenous isotope, respectively, as derived from fig

However, the

1 B). Knowledge of total bile output is necessary for calculation of total biliary isotope excretion rates, since T-tube bile drainage is usually incomplete. Accurate estimation of total bile output in individuals is difficult, but by assuming a mean total 24 h bile output of only 500 al may have underestimated the corrected total excretion rate. Published figures for total daily bile volume in normal man vary considerably (from 600 to 2400 ml5-7); our observation of 24 h T-tube bile volumes up to 900 ml indicates that 24 h volumes well above 500 ml may be encountered. Whilst we agree with Clements et al that present evidence does not support the concept of a large conservative enterohepatic circulation of 25-OHD, the possibility of a small, but functionally significant, conservative circulation should not be dismissed. The absence of significant amounts of free 25-OHD in bile does not exclude a conservative enterohepatic circulation since biliary products may be metabolised in the small intestine, releasing 25-OHD which would then be available for reabsorption. A small conservative enterohepatic circulation of 25-OHD might well become functionally significant in the presence of two coexisting factors-one is increased faecal metabolite loss due to malabsorption8or high fibre intake,9,10 and the other is low or borderline endogenous vitamin D synthesis.ll Under these circumstances, increased losses of 25-OHD from an enterohepatic circulation might, over a period of time, be an important factor in the development of vitamin D deficiency.

ml Clements

et

biliary isotope

Department of Pathology, Welsh National School of Medicine, Heath Park, Cardiff CF4 4XW

J. COMPSTON

Gastro Intestinal Research Unit,

Rayne Institute, St Thomas’ Hospital, London SE1 7EH

JULIA E. LEDGER

PA, Kodicek E. Investigations on metabolites of vitamin D in rat bile: Separation and partial identification ofa major metabolite. Biochem J 1969; 115: 663-69 2. Mawer EB, Backhouse J, Holman CA, Lumb GA, Stanbury SW. The distribution and storage of vitamin D and its metabolites in human tissues. Clin Sci 1972; 43: 413-31. 3 Avioli LV, Lee SW, McDonald JE, Lund J, De Luca HF. Metabolism of vitamin D3-3H in human subjects: Distribution in blood, bile, feces and urine. J Clin Invest 1. Bell

1967; 46: 983-92. 4 5.

Ledger JE, Compston JE. Biliary tritium excretion after intravenous administration of 3H-25-hydroxyvitamin D3 in man. Clin Sci 1983; 64: 26P. Paumgartner G, Sauerbruch T. Secretion, composition flow of bile. In: Classen M, Schreiber HW, eds. Clinics in gastroenterology: Vol 12 (no 1). London: WB

Saunders, 1983: 3-23. 6. Doubliet H, Fishman L. Human biliary-pancreatic secretion. Am J Gastroenterol 1961, 35: 499-512 7. Schoenfield LJ. Diseases of the gallbladder and biliary system. New York John Wiley & Sons, 1977: 45. 8. Compston JE, Merrett AL, Ledger JE, Creamer B. Faecal tritium excretion after intravenous administration of 3H-25-hydroxyvitamin D3 in control subjects and in patients with malabsorption. Gut 1982; 23: 310-15. 9. Batchelor AJ, Compston JE. Reduced plasma half-life of radiolabelled 25-hydroxyvitamin D3 in subjects receiving a high-fibre diet. Br J Nutr 1983, 49: 213-16. 10 Dunnigan MG, McIntosh WB, Ford JA, Robertson I. Acquired disorders of vitamin D metabolism. In: Clinical endocrinology 2: Calcium disorders London Butterworths, 1982: 125. 11. Davie MWJ, Lawson DEM, Emberson C, Barnes JLC, Roberts GE, Barnes ND Vitamin D from skin: Contribution to vitamin D status compared with oral vitamin D in normal and anti-convulsant-treated subjects. Clin Sci 1982; 63: 461-72

NON-SURGICAL SEPARATION OF PREPUTIAL ADHESIONS

after incubation with

reported similar results after parenteral administration of 3H-25-OHD3 to post-cholecystectomy patients with T-tube drainage.4Clements et al claim that the use of human plasma protein fraction as a vehicle for injection of the isotope approximates more closely to physiological conditions than do ethanol-saline, ’Intralipid’, or propyleneglycol, and this, they suggest, may explain the high biliary excretion rate described in studies, including ours, in which ethanol-saline was used.

and Mr Freeman (Aug 11, p 344) make some well worth trying out. I am surprised, however, helpful suggestions that they make no mention of sedation-only parental attempts to distract and professional "reassurance". Trimeprazine (as ’Vallergan Forte’) 1’ 5 mg/kg works a treat and helps the child, his parents, and the doctors.

SIR,—Mr Griffiths

DAVID MORRIS