MYOCARDIAL CARNITINE DEFICIENCY IN ACUTE MYOCARDIAL INFARCTION

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<ul><li><p>1419</p><p>of system involvement and with presentation either in childhood orin adulthood, treatment would generally be in conjunction withother specialists. Seeing patients together in combined clinicswould seem to be the best way of achieving this.There is an air of defeatism related to many lethal or seriously</p><p>handicapping genetic disorders. Clinical geneticists must notencourage this by being satisfied to limit their involvement todiagnosis and genetic counselling.</p><p>Royal Manchester Childrens Hospital,Manchester M27 1FG M. SUPER</p><p>PHENYLPROPANOLAMINE AND BLOOD PRESSURE</p><p>SIR,-Although phenylpropanolamine (PPA) has been safely usedin the U.S.A. for over forty years as a nasal decongestant, your April10 editorial raised the possibility that PPA in weight controlpreparations could produce increased blood pressure.In the past two years, I have done three large studies in our obesity</p><p>clinic in San Francisco of the effects of three dosage forms of PPA.More than 400 obese patients were studied. The results will bepublished elsewhere.Data were gathered on a twelve-week, double-blind,</p><p>placebo controlled study of 50 mg PPA three times daily(twice the recommended dose for weight loss); a double-blind,placebo controlled study of 50 mg PPA combined with 200 mgcaffeine in controlled-release form; and a single-blind trial of 75 mgPPA in controlled-release form.</p><p>All three dosages caused no significant increase in blood pressurein more than 400 patients. 2 patients experienced noteworthy risesin blood pressure after treatment with 75 mg PPA, but theseincreases were felt not to be drug related.The mean pooled systolic and diastolic blood pressure in the 50</p><p>mg x 3 PPA/placebo study are shown in the figure.Our results confirm that PPA does not cause a significant increase</p><p>in blood pressure even when the amount ingested (150 mg/day) issubstantially higher than the recommended 75 mg dose. There was,on the contrary, a reduction in blood pressure as the studies</p><p>progressed.Cathedral Hill Obesity Clinic,San Francisco, California 94103, U.S.A. RUDOLF E. NOBLE</p><p>Mean systolic and diastolic blood pressure.</p><p>CEFTAZIDIME AND SALMONELLA</p><p>SiR,-Dr Gozzard and colleagues (May 22, p. 1152) listed aSalmonella newport septicaemia treated with ceftazidime 1 g threetimes daily as a failure. The minimum inhibitory concentration forthat strain was 0 - 2 5 lAg/ml. Probably the dosage was too low. Wehave treated a 33-year-old African man, who had sickle cell anaemiaand an osteomyelitis with S. typhimurium (MIC 0-25 J.lg/ml),successfully with, at first, 2 g twice daily for 17 days and, after anoperation, 3 g twice daily for 25 days. The bone marrow sampletaken during operation was sterile. A higher dosage is probablyrequired in Salmonella (and, possibly, Shigella) infections. Ofinterest would be information on susceptibility of the isolatedorganisms to other currently available antibiotics and successfultreatment of the infections by ceftazidime, where prior antibiotictherapy had failed.Infection Laboratory,Johann Wolfgang GoetheUniversity Clinic,</p><p>6000 Frankfurt-am-Main 70,West Germany</p><p>PRAMOD M. SHAHWOLFGANG STILLE</p><p>MYOCARDIAL CARNITINE DEFICIENCY IN ACUTEMYOCARDIAL INFARCTION</p><p>SIR,-Dr Suzuki and colleagues (Jan. 9, p. 116) reported decreasedlevels of free L-carnitine in the myocardium of chronic heart failurepatients and a concomitant rise in acylcarnitine. These changes arerelated to a removal of accumulated free fatty acid (FFA) and long-chain acyl-CoA esters secondary to chronic hypoxia which in turninhibits adenine nucleotide translocase. This metabolic device,also observed in dog hearts during the reversible phase ofischaemia2 seems to act as a servo mechanism tending to relievemyocardial injury. Suzuki et al. suggested the administration ofexogenous L-carnitine during acute and chronic cardiac ischaemia.In acute experimental ischaemia, however, progressively more totalL-carnitine is lost the longer the ischaemia lasts.2 The two findingsstrongly suggest that the maintenance of physiological levels ofL-carnitine and the acylcarnitine to free carnitine ratio play animportant role in the control of the metabolism of the injuredmyocardium.We measured3,4 heart L-carnitine levels at necropsy in seven</p><p>patients who had had acute myocardial infarctions and in four whohad died from causes other than heart disease. In the first group thetissue samples were removed from the necrotic area, from the borderzone, and from the healthy myocardium; whereas in the controlsL-carnitine levels were separately determined in specimens takenfrom the left ventricular wells. The necrotic myocardial areas hadlower L-carnitine levels, while the border zone tissue showedintermediate values between necrotic and healthy surroundingtissue levels. There was no discrepancy between the myocardialL-carnitine values in the controls and those found in the healthysurrounding tissue of those who had died from myocardialinfarction.We did not observe short and long chain carnitine esters in the</p><p>tissue fragments of either group, presumably because in specimensremoved 24 h after death all the L-carnitine content is present in thefree isomer form, as a result of hydrolysis during the period sincedeath and during storage at -25C for 10-15 days. Therefore, inour experimental model free L-carnitine corresponds to totalcarnitine. This statement is supported by the fact that the tissueL-carnitine levels we found in the healthy myocardium wereidentical to the total L-carnitine levels mesured by Cederblad in themyocardium of heart surgery patients. 5</p><p>1. Shug AL, Shrago E, Bittar N, Folts JD, Koke JR. Acyl-CoA inhibition of adeninenucleotide translocation in ischemic myocardium. Am J Physiol 1975; 228: 689.</p><p>2. Shug AL. Changes in tissue levels of carnitine and other metabolites during myocardialischemia and anoxia. Arch Biochem Biophys 1978; 187: 25.</p><p>3. Pearson DJ, Tubbs PK, Chase JFA. Carnitine and acetyl carnitine. In BergmeyerMU, ed. Methods of enzymatic analysis: Vol IV New York: Academic Press, 1974:1758.</p><p>4. Seccombe DW, Dodek P, Frolich J, Hahn P, Skala JP, Campell DJ. Automated methodfor 1-carnitine determination Clin Chem 1976; 22: 1589</p><p>5. Cederblad G, Lindstedt S, Lundholm K. Concentration of carnitine in human muscletissue. Clin Chim Acta 1974; 53: 311.</p></li><li><p>1420</p><p>LEVELS OF L-CARNITINE IN HUMAN MYOCARDIUM OF THE LEFT</p><p>VENTRICLE</p><p>Our data confirm L-carnitine depletion in necrotic areas ofmyocardium and suggest that the intermediate L-carnitine values(see table) found in the infarct border zones reflect an area ofreversible metabolic injury for which restoration of adequateL-carnitine levels could protect the myocardium from damagecaused by accumulation of FFA and long-chain acyl-CoA esters.</p><p>Institute of Anatomyand Pathological Histology II,</p><p>Department of Ultrastructural Pathology,University of Rome,</p><p>Rome, Italy 00161</p><p>LUIGI GIUSTO SPAGNOLIMARCO CORSISERGIO VILLASCHIGIAMPIERO PALMIERIFRANCO MACCARI</p><p>MEASLES VACCINE VERSUS INOSIPLEX</p><p>SIR,-Your editorial (May 8, p. 1052) on inosiplex, particularly inrelation to treatment ofsubacute sclerosing panencephalitis (SSPE),forcefully illustrates that we are, sadly, still preoccupied withtreatment rather than prevention. The most contentious commentis: "... meanwhile patients continue to fall sick with what is ahorrible and usually seriously progressive disease". Moreover, youthen go on to suggest that what is needed is "a mode of treatmentthat will deal rapidly with... the disease". Nowhere is it mentionedthat measles vaccination is a far more efficient weapon againstSSPE, although there is now good evidence 1,2 that, by controllingmeasles, the subsequent development of SSPE is prevented. Thesmall number of cases in vaccinated children may well beattributable to a natural attack of measles before vaccination,2 and inthe U.S.A., where considerable progress has been made towards theeradication of measles, cases of SSPE have declined in number. 3</p><p>There is now no excuse for patients to "continue to fall sick".The benefit-cost ratio for measles vaccine in Western countries is</p><p>about 10 to 1.4,5 El06 has estimated that control or eradication ofSSPE will increase the benefit by at least 10%. While inosiplex maybe useful for other slow virus infections, a drug that produces "ahighly statistically significant" improvement in survival of 21 Iyears in a disease showing such wide variations in its natural courseis less than impressive. Our priorities should lie in improving thepoor measles vaccine acceptance rate in the U.K., rather than inseeking a drug for treatment of a preventable infection.</p><p>P.H.L.S. Communicable DiseaseSurveillance Centre,</p><p>London NW9 5EQ</p><p>P.H.L.S. Epidemiological Research Laboratory,Central Public Health Laboratory,London NW9</p><p>NORMAN D. NOAH</p><p>CHRISTINE L. MILLER</p><p>1. Modlin JF, Jabbour JT, Witte JJ, Halsey NA. Epidemiological studies of measles,measles vaccine and SSPE. Pediatrics 1977; 59: 505-12.</p><p>2. Centers for Disease Control Subacute sclerosing panencephalitis and measles.MMWR 1977; 26: 309-10.</p><p>3. Centers for Disease Control. Measles prevention. MMWR 1982, 31: 217-31.4. Witte JJ, Axnick NW. The benefits from 10 years of measles immunisation in the</p><p>United States. Publ Hlth Rep (Wash) 1975; 90: 205-07.5. Creese AL, Henderson RH. Cost-benefit analaysis and immunisation programmes in</p><p>developing countries. Bull WHO 1980; 58: 491-97.6. Elo O. Cost-benefit studies of vaccinations in Finland. Devel Biol Standard 1979; 43:</p><p>419-28.</p><p>POSTSPLENECTOMY INFECTIONS</p><p>SIR,-Polyvalent pneumococcal-polysaccharide vaccines toprotect children who are splenectomised or for whom a splen-ectomy is planned has reduced the risk of infection by Strepto-coccus pneumoniae. Immunisation before splenectomy is recom-mended because some patients immunised afterwards havecontracted this infection,2 and the IgM and IgG responses arereduced in patients immunised after splenectomy. Infection inimmunised patients can occur even if the pneumococcal type ispresent in the vaccine and even if the antibody titre ishigh4,5-which demonstrates the complexity of the mechanismsinfluencing the immunity of splenectomised patients.</p><p>It might be of interest to see what happened in a series of- unimmunised children from the pre-vaccine era where the outcome</p><p>in terms of septicaemia due to Strep. pneumoniae was good. At theAurora Hospital, Helsinki, 69 children were splenectomised in theyears 1956-76 because of trauma (48 children), hereditaryspherocytosis (9), non-spherocytic haemolytic anaemia (1),autoimmune haemolytic anaemia (3), and idiopathicthrombocytopenic purpura (4), and 4 children were splenectomisedin connection with partial pancreatectomy because ofhyperinsulinism. The age at operation was 4 months to 14 years; 9children were younger than 4 years. No prophylactic penicillin wasgiven after splenectomy. The follow-up time was 5-10 months in 5children, 17 and 19 months in 2 children, and 2-24 years in 53children, altogether 354 patient-years. 8 children were notcontacted.</p><p>1 patient aged 6 months with a damaged spleen died during thefirst postoperative day because of other injuries sustained in anaccident. The postoperative course in the remaining 68 childrenwas uncomplicated. Another infant with trauma, aged 4 months atoperation, died 10 months later because of sepsis caused bymeningococcus. The child had been left without treatment becausethe disease was thought to be a viral infection. Sepsis caused bymeningococcus is not an uncommon disease in children of this agegroup. It can be fatal, even with proper treatment, in children whostill have a spleen. 1 child, 11 years old, had sepsis due to Strep.pneumoniae 21 months after splenectomy. She recovered and wasstill well 6 years after this episode.Thus there has been only one infection caused by Strep.</p><p>pneumoniae in 55 children followed up for 17 months to 24 years. 5children were followed up for 5-10 months only, but this is thoughtto be the high risk period after splenectomy.This result seems good. Most of the conditions for which</p><p>splenectomy was required were of the kind where the risk ofpostsplenectomy infection is lower than it is in other conditions.Only 3 children had AIHA (where the risk is higher), and thechild wth the pneumococcal infection belonged to this group.Another child who had her spleen removed because of severe AIHAat the age of 21 months was still well 13 years later, and the thirdAIHA patient, aged 6 years at operation, was well after 24 years.The high standard of nutrition and hygiene in Finnish children,</p><p>as a result of a well developed infant and child health careprogramme, may have contributed to resistance against infections,but this is difficult to evaluate.When results of immunisation with pneumococcal vaccine are</p><p>assessed it will, I think, be important to remember pre-vaccine serieswhere Strep. pneumoniae infection in unimmunised children wasuncommon. Incidentally, a more conservative approach to spleeninjury is used these days.6 Either the damaged part of the spleen is</p><p>1. Amman AJ, Addiego J, Wara DW, Lubin B, Smith WB, Mentzer WC Polyvalentpneumococcal-polysaccharide immunization of patients with sickle-cell anaemiaand patients with splenectomy. N Engl J Med 1977; 297: 897-900.</p><p>2. Dickerman JD. Splenectomy and sepsis: a warning. Pediatrics 1979; 63: 938-41.3. Hosea SW, Brown EJ, Burch CG, Berg RA, Frank MM Impaired immune response of</p><p>splenectomised patients to polyvalent pneumococcal vaccine. Lancet 1981; i:804-07.</p><p>4 Giebink GS, Schiffman G,Krivit W, Quie PG. Vaccine type pneumococcal pneumoniaoccurrence after vaccination in an asplenic patient JAMA 1979; 241: 2736-37.</p><p>5. Minor DR, Schiffman G, McIntosh LS. Response of patients with Hodgkins disease topneumococcal vaccine. Ann Intern Med 1979; 90: 887-92.</p><p>6. Wesson DE, Filler RM, Ein SH, Shandling B, Simpson JS, Stephens CA. Rupturedspleen. When to operate? J Pediair Surg 1981; IS: 324-26.</p></li></ul>