850

against coronary-artery disease in about 13,000 males, 50-59years of age. This latter study has been organised by a researchcommittee, and the first results will probably be available nextspring.

P. A. OWRENA. HELLEMA. ØDEGAARD.

University Hospital (Rikshospitalet),Oslo, Norway.

ADENOSINE AND PLATELET ADHESIVENESSSIR,-Dr. Philp and Dr. Payling Wright (July 31) deter-

mined, in normal fasting subjects, platelet-counts and plateletadhesiveness, which decreased and increased respectively dur-ing alimentary lipxmia. The addition of adenosine decreasedplatelet adhesiveness in fasting blood; this effect was greatlydiminished during lipxmia.

Lillehei and I 1 2 have shown that the phosphatases are theprime movers in the activation of profibrinolysin to fibrinolysin(with coenzymes).Quick 3 tried to determine the mode of action, in relation to

the coagulation mechanism, of A.T.P. (adenosine triphosphate)which, in vitro, showed activity at the same level as that atwhich it is present physiologically in normal blood. He statedthat " the results obtained with the thrombin time clearlyindicate that the action is on fibrinogen ". Nevertheless, Quickhimself clearly demonstrated that the action of A.T.P. was dueto the digestion of fibrin. Although he labelled A.T.P. as ananticoagulant, its primary action is that of fibrinolysis-thussecondarily becoming an anticoagulant in the maintenance ofblood-fluidity. On my own,4.; and with Shafiroff, I haveshown that A.T.P. is an activator of the fibrinolytic mechanism.Hence the decreased adhesiveness of platelets is due to

A.T.P.’s activation of the fibrinolytic mechanism. Lipaemiainhibits this mechanism, thus causing decreased platelet-countsand increased adhesiveness. A.T.P. is the main factor whichmaintains the blood-fluidity in man within physiological levels. 4

New York, 23, New York. Y. I. MISIRLIOGLU.Y. I. MISIRLIOGLU.

ISCHÆMIC FOREARM BLOCK

SIR,-One of the commonest complications of ischxmic armblock is reaction to systemic release of large quantities of localanxsthetic on release of the tourniquet. This is most easilyprevented by reducing the amount of local anxsthetic used, butbelow a certain quantity satisfactory anaesthesia is not obtainedexcept by reducing the volume of tissue to be anxsthetised.

In operations confined to the hand, which account for manyof the procedures suitable for ischaemic block, the volume oftissue requiring anaesthesia can be reduced by carrying outa forearm block. This differs from the method described byHolmes only in that the tourniquet is applied to the upperforearm instead of above the elbow and consequently a smallerquantity of local anaesthetic is used. Full anxsthesia can beobtained by injecting 10-14 ml. of 0’5% lignocaine into a veinon the dorsum of the hand. This technique has been appliedto about 50 cases in the accident department of the AucklandHospital, and previously in the septic hand clinic at St. George’sHospital, London.No adverse reactions have occurred on releasing the

tourniquet; irregularities and changes in the rate of the pulsehave not occurred, and no patient has reported dizziness orfaintness on direct questioning. No complications, eitherimmediate or late, have occurred from having a tourniquetround the forearm.For procedures lasting more than 10 minutes the double-

tourniquet method can be used with one tourniquet above andone below the elbow, the lower tourniquet being inflated andthe upper one deflated when analgesia is obtained, in about 2 to5 minutes. This method requires 14-20 ml. of0’5°o lignocainefor adequate anxsthesia. Larger quantities have proved1. Misirlioglu, Y. I., Lillehei, C. W. Angiology, 1962, 13, 185.2. Misirlioglu, Y. I., Lillehei, C. W. J. Am. med. Ass. 1963, 184, 211.3. Quick, A. J. Nature, Lond. 1963, 200, 469.4. Misirlioglu, Y. I. Lecture given at the Unity Hospital, Brooklyn, New

York, on July 18, 1964.5. Misirlioglu, Y. I. Summary, 1964, 16, 67.6. Misirlioglu, Y. I., Shafiroff, B. G. Circulation, 1964, 30, suppl. 3, p. 20.7. Holmes, C. McK. Lancet, 1963, i, 245.

unnecessary except where there has been technical failure suchas perivenous injection or deflation of a faulty cuff; and themaximum volumes mentioned have been used only on largemen. These volumes are comparable with those named byvan Niekerk and Coetzee for intra-arterial ischxmic blockwithout the problems associated with arterial injection.These techniques of course do not provide full muscle

relaxation since the proximal parts of the forearm muscles areabove the tourniquet. This is no disadvantage, as the patientcan position his hand and move it when requested.

D. S. ROBERTSON.

Auckland Hospital,Park Road,

Auckland, C.3,New Zealand.

AMITRIPTYLINE AND IMIPRAMINE POISONING

SIR,-Amitriptyline and imipramine are absorbed quicklyfrom the intestinal tract, and they are largely bound to plasma-proteins. They accumulate rapidly in various tissues; so thatthe serum-concentration can never be high. After mediumtoxic doses the tissue concentration is 10-30 times that of theserum-concentration. After demethylation and glucuronisationin the liver they are excreted in the urine, and hydroxylationtakes place.in the liver and tissues. This happens quickly, andno drug can be found in the tissues 24 hours after administra-tion of medium toxic doses. Only small and unimportantamounts of free drug can be found in the urine after administra-tion of high doses.

Blood-clearing methods, such as dialysis and peritonealdialysis,9 10 are theoretically and practically of no value.

Clinically my colleagues and I found forced diuresis to be of notherapeutic help, although we did not measure the excretionquantitatively. Rabbits who received 50 mg. per kg. of ami-triptyline intraperitoneally were treated with mannitol, andurinary excretion of the drug was found to be below 2 Theforced diureses reported by Dr. Stark and Dr. Bethune

(Aug. 21) we feel were effective as treatment of the poisoningcaused by amylobarbitone only. This view is supported by thefact that the patient was unconscious for 5 days. In our

experience the course of poisoning with the thymolepticgroup of drugs is rapid; the life-threatening symptoms,cerebral excitation, and heart-damage occur within 24 hours,and the period of unconsciousness is of almost the sameduration.

Since 1959 we have treated in this department 38 cases ofamitriptyline poisoning (the largest ingested amount was about3 g., in a patient who died) and 29 cases of imipramine poison-ing (the largest ingested amount was 4700 mg., and 1 patientdied).Many clinical findings suggest an atropine-like effect of the

thymoleptic group of drugs. Pyridostigmine in small doses(about 0-010 mg. per kg.) has been reported to reduce thefatality-rate in mice who received L.D’100 of amitriptyline to25 %12. Rabbits who received 50 mg. per kg. of amitriptylineintraperitoneally developed severe atrioventricular bundle-branch block corresponding to the results in man where theylead to forward cardiac failure. Pyridostigmine has some effectin restoring these findings to normal.11We treat convulsions with phenobarbitone as a prophylactic

basic narcotic, and use pentobarbitone for further narcosis asrequired. Our present principles in treatment, which we haveapplied in only 1 patient, are best illustrated by the case wereport here.

An otherwise healthy 41-year-old man, with no history ofprevious disease or disposition to disease, was admitted tohospital at least 2 hours after the ingestion of 4700 mg. ofimipramine. On admission he was unconscious, and after a fewminutes he developed tonic convulsions for 30 seconds. The

blood-pressure was 70/50 mm. Hg, pulse-rate 84, and heart-8. van Niekerk, J. P. de V., Coetzee, T. ibid. 1965, i, 1353.9. Sunshine, P., Yaffe, S. J., Alto, P. Am. J. Dis. Child. 1963, 106, 501.

10. Harthorne, J. W., Marcus, A. M., Kaye, M. New Engl. J. Med. 1963,268, 33.

11. Rasmussen, J., Nymark, M. Unpublished.12. Scharer, K. Schweiz. med. Wschr. 1965, 95, 173.