ADRENALINE AND ISOPRENALINE IN MYOCARDIAL FAILURE

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fortune, the Apothecaries Hall, and a great deal more ofold London were swept away by fire during a Septemberweekend in 1666. But the Society which he helped tofound has endured.

ULCERATIVE COLITISAND CHRONIC LIVER DISEASE

THE association of ulcerative colitis with hepaticcirrhosis poses some intriguing questions. Are theycausally related, and, if so, does cirrhosis lead to colitis, orcolitis to cirrhosis ? It is always difficult with problems ofthis kind for any one group of investigators to assembleenough data. Even a unit as highly specialised in the studyof cirrhosis as that of Prof. Sheila Sherlock at the RoyalFree Hospital, London, could muster only 22 cases ofcolitis with chronic hepatic disease in the five years from1959 to 1963,1 but their studies have led to some interestingconclusions.

The incidence of ulcerative colitis in the generalpopulation is only about 0-1%, but in their series of over500 cases of liver-disease it was about 4%, strongly sug-gesting that the two conditions were related. Which camefirst is less obvious, but since the colitis was recognisedfirst in 15 of the 22 cases, involvement of the liver may wellhave been secondary to disease of the colon.

Histological studies of the affected livers were revealing.Of the 22 patients, 20 had hepatic cirrhosis-in 19 of themapparently postnecrotic. This points to the nutritionalimpairment associated with ulcerative colitis as a causativefactor. Although there is little evidence that in mannutritional deficiency alone can cause hepatic necrosiswith consequent cirrhosis, nutrition is an important factorin the pathogenesis of hepatic disorders. The resistance ofthe liver to a variety of toxic agents, biological as well aschemical, is largely determined by the general state ofnutrition and especially the intake of protein. Some atleast of the cases of postnecrotic cirrhosis might thereforebe attributed to attacks of viral hepatitis in patientsnutritionally depleted by their ulcerated colons.

In more than half of a control group, cirrhosis did notstart until after the age of forty-five years; but among the22 patients with cirrhosis and colitis, the cirrhosis startedin 12 under the age of twenty-six, and in no less than 19under forty-six. Willocx and Isselbacher 3 found 7 casesof colitis amongst 33 patients with cirrhosis under the ageof forty, but not a single case amongst 143 over that age.The reasons are not yet known, but the higher incidenceof autoantibodies in juvenile than in adult colitis 4 5 maybe one.

On the other hand, colitis and postnecrotic cirrhosismight have a common cause. Both conditions could arisefrom autoantibodies directed against the colon and theliver. Some people appear to form such autoamibodiesmore readily than others, and in greater variety. Thecirrhosis associated with colitis seems to be usually of thepostnecrotic type-in which evidence of autoimmunity isespecially common.’ The lymphocytes and plasma-cells

1. Holdsworth, C. D., Hall, E. W., Dawson, A. M., Sherlock, S. Q. JlMed. 1965, 34, 211.

2. Himsworth, H. P. The Liver and its Diseases. Oxford, 1947.3. Willocx, R. G., Isselbacher, K. J. Am. J. med. 1961, 30, 185.4. Broberger, O., Perlmann, P. J. exp. Med. 1959, 110, 657.5. Asherson, G. L., Broberger, O. Br. med. J. 1961, i, 1429.6. Glynn, L. E., Holborow, E. J. Autoimmunity and Disease. Oxford,

1965.7. MacKay, I. M., Wood, I. J. in Progress in Liver Diseases (edited by

H. Popper and F. Schaffner); p. 39. New York, 1961.

often described in these cases also suggest some kind ofimmune reaction; but their presence does not, of course,indicate the origin of the antigen to which they are pre-sumably reacting, which could as well be exogenous-e.g.,a virus-as autogenous.

Lastly, a diseased liver might harm the colon, althoughthe extreme rarity of colitis in alcoholic cirrhosis excludesany simple relationship such as a predisposition to ulcera-tion because of the vascular stasis of portal hypertension.Lesions in the colon have, however, been described infatal cases of viral hepatitis,8 and while their pathogenesisis still unexplained colitis may sometimes be secondaryto hepatic disease.

ADRENALINE AND ISOPRENALINE

IN MYOCARDIAL FAILURE

ISOPRENALINE has complex effects on the myocardium.In the normal heart it produces a decrease in left ventricu-lar volume, an increased stroke volume, and an increasedrate of ejection. Myocardial oxygen consumption isincreased.9 Dynamic obstruction of the left ventricle maybe produced in the anatomically normal heart.10 11

In this issue Prof. Mary Lockett discusses the effects ofisoprenaline in experimentally induced myocardial failure.This work was stimulated by an account 12 of three patientswith status asthmaticus who died suddenly after injec-tions of adrenaline given soon after they had taken

isoprenaline. Unfortunately no details of the doses ofadrenaline or routes of administration of isoprenalinewere given. Professor Lockett has compared the effects ofisoprenaline hydrochloride and orciprenaline in heart-

lung preparations in which she varied the load on theheart. She found that a fifteenth of a dose of isoprenalinewithout deleterious effect on healthy hearts was sufficientto produce cardiac arrest in the failing hearts. It wasabout six times as potent as orciprenaline in all prepara-tions. She suggests that adrenaline increases the load onthe heart by increasing venous return and so provokinga situation in which isoprenaline may produce cardiacarrest. She does not, however, comment on the cardiacanoxia associated with status asthmaticus, which may bean important contributing factor.The possible incompatability between adrenaline and

isoprenaline in patients with limited cardiac reserve hasbeen known and taught for many years, but it is evidentlynot yet as widely recognised as it should be. McManis 11rightly insists that they should not be given together, andthat patients should be asked whether they have recentlyused preparations of isoprenaline and orciprenaline beforean injection of adrenaline is given. Although ProfessorLockett does not describe the effects of blocking &bgr;-adren-efgic receptors with an agent such as propranolol, itwould seem reasonable to give one intravenously if thiscatastrophe occurs.

Lord BROCK has been re-elected president of the RoyalCollege of Surgeons of England. He has chosen as his titleBaron Brock of Wimbledon in the London borough ofMerton.

Prof. VTIILSON SMITH, who held the chair of bacteriology atUniversity College Hospital Medical School, London, from1946 to 1960, died on July 10.8. Lucke, B. Am. J. Path. 1944, 20, 471.9. Krasnow, N., Rolett, E. L., Yurchak, P. M., Hood, W. B., Gorlin, R.

Am. J. Med. 1964, 37, 514.10. de Bono, A. H., Proctor, E., Brock, R. Guy’s Hosp. Rep. 1965, 114, 4.11. See Lancet, 1965, i, 1261.12. McManis, A. G. Med. J. Aust. 1964, ii, 76.