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Cardiac effects of carnitine deficiency induced by antibiotics containing pivalic acid in children

Published online by Cambridge University Press:  19 August 2008

Kate Abrahamsson ,
Mats Mellander ,
Bengt O. Eriksson ,
Elisabeth Holme ,
Ulf Jodal  and
Sven Lindstedt
Kate Abrahamsson*
Affiliation:
Department of PediatricsGothenburg University, Gothenburg, Sweden
Mats Mellander
Affiliation:
Department of PediatricsGothenburg University, Gothenburg, Sweden
Bengt O. Eriksson
Affiliation:
Department of PediatricsGothenburg University, Gothenburg, Sweden
Elisabeth Holme
Affiliation:
Department of Clinical Chemistry, Gothenburg University, Gothenburg, Sweden
Ulf Jodal
Affiliation:
Department of PediatricsGothenburg University, Gothenburg, Sweden
Sven Lindstedt
Affiliation:
Department of Clinical Chemistry, Gothenburg University, Gothenburg, Sweden
*
K Abrahamsson, Department of Clinical Chemistry, Sahlgren's Hospital, S-413 45 Gothenburg, Sweden. Telephone: +46-31602426. Fax number: +46-31827610
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Abstract

We studied echocardiographically 17 children with depletion of carnitine due to treatment over 1–3 years with antibiotics containing pivalic acid. When the children were depleted of carnitine, the left ventriclar posterior wall was significantly thickened in diastole when compared to a reference group. Six months later, after normalisation of the concentrations of carnitine, the left ventricular posterior wall was significantly thinner and did not differ from the reference group. We conclude that drugs containing pivalic acid, when given for several months, decrease the stores of carnitine to levels where cardiac involvement occurs.

Keywords

Heartpivmecillinamchildrencardiac effects
Type
Original Articles
Information
Cardiology in the Young , Volume 7 , Issue 2 , April 1997 , pp. 178 - 182
Copyright
Copyright © Cambridge University Press 1997

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References

1Vickers, S, Duncan, CAH, White, SD, Ramjit, HG, Smith, JL, Walker, RW, Flynn, H, Arison, BH. Carnitine and glucuronic acid conjugates of pivalic acid. Xenobiotica 1985; 15: 453–458.CrossRefGoogle ScholarPubMed
2Melegh, B, Kerner, J, Bieber, LL. Pivampicillin-promoted excretion of pivaloylcarnitine in humans. Biochem Pharmacol. 1987; 36: 3405–3409.CrossRefGoogle ScholarPubMed
3Holme, E, Greter, J, Jacobson, C-E, Lindstedt, S, Nordin, I, Kristiansson, B, Jodal, U. Carnitine deficiency induced by pivampicillin and pivmecillinam therapy. Lancet. 1989; ii: 469–473.CrossRefGoogle Scholar
4Holme, E, Jodal, U, Lindstedt, S, Nordin, I. Effects of pivalic acid-containing prodrugs on carnitine homeostasis and on response to fasting in children. Scand J Clin Lab Invest. 1992; 52: 361–372.CrossRefGoogle ScholarPubMed
5Bremer, J. Carnitine-metabolism and functions. Physiol Rev. 1983; 63: 1420–1480.CrossRefGoogle ScholarPubMed
6Abrahamsson, K, Eriksson, BO, Holme, E, Jodal, U, Lindstedt, S, Nordin, I. Effects of 12 days Pivmecillinam treatment on response to fasting in adults. Biochem Med Metab Biol 1994; 52: 18–21.CrossRefGoogle Scholar
7Engel, AG, Rebouche, CJ. Carnitine metabolism and inborn errors. J Inherit Metab Dis. 1984; Suppl 1: 41–66.Google ScholarPubMed
8Rebouche, CJ, Engel, AG. Kinetic compartmental analysis of carnitine metabolism in the human carnitine deficiency syndromes. J clin Invest. 1984; 73: 857–867.CrossRefGoogle ScholarPubMed
9Cederblad, G, Lindstedt, S. A method for the determination of carnitine in the picomole range. Clin chim Acta. 1972; 37: 235–243.CrossRefGoogle ScholarPubMed
10Sahn, DJ, De Maria, A, Kisslo, J, Weyman, A. Recommendations regarding quantitation in M-mode echocardiography: Results of a survey of echocardiographic measurements. Circulation. 1978; 58: 1072–1083.CrossRefGoogle ScholarPubMed
11Rogé, CLL, Silverman, NH, Hart, PA, Ray, RM. Cardiac structure growth pattern determined by echocardiography. Circulation. 1978; 57: 285–290.CrossRefGoogle ScholarPubMed
12Bradley, JW. Distribution-free staisical tests. Prentice-Hall, London; 1968: 68–86.Google Scholar
13Eriksson, BO, Lindstedt, S, Nordin, I. Hereditary defect in carnitine membrane transport is expressed in skin fibroblasts. Eur J Pediatr. 1988; 147: 662–663.CrossRefGoogle ScholarPubMed
14Eriksson, BO, Gustafson, B, Lindstedt, S, Nordin, I. Transport of carnitine into cells in hereditary carnitine deficiency. J Inherited Metab Dis. 1989; 12: 108–111.CrossRefGoogle ScholarPubMed
15Tein, I, De Vivo, DC, Bierman, F, Pulver, P, De Meirleir, LJ, Cvitanovicsojat, L, Pagon, RA, Bertini, E, Dionisi-Vici, C, Servidei, S, Dimauro, S. Impaired skin fibroblast carnitine uptake in primary systemic carnitine deficiency manifested by childhood carnitine-responsive cardiomyopathy. Pediatr Res. 1991; 28: 247–255.CrossRefGoogle Scholar
16Stanley, CA, DeLeeuw, S, Coates, PM, Vianey-Liaud, C, Divry, P, Bonnefont, JP, Saudubray, JM, Haymond, M, Trefz, FK, Breningstall, GN, Wappner, RS, Byrd, DJ, Sansaricq, C, Tein, I, Grover, W, Valle, D, Rutledge, SL, Treem, WR. Chronic cardiomyopathy and weakness or acute coma in children with a defect in carnitine uptake. Ann Neurol. 1991; 30: 709–716.CrossRefGoogle ScholarPubMed
17Garavaglia, B, Uziel, G, Dworzak, F, Carrera, F, DiDonato, S. Primary carnitine deficiency: Heterozygote and intrafamilial phenotypic variation. Neurology 1991; 41: 1691–1693.CrossRefGoogle ScholarPubMed
18DiDonato, S, Garavaglia, B, Rimoldi, M, Carrera, F: Clinical and biomedical phenotypes of carnitine deficiencies. In: Ferrari, R, DiMauro, S, Sherwood, G, ed. L-Carnitine and its role in medicine: From function to therapy. Academic Press, New York, NY; 1992: 81–98.Google Scholar
19Moore, R, Glasgow, JF, Bingham, MA, Dodge, JA, Pollitt, RJ, Olpin, SE, Middleton, B, Carpenter, K. Long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency diagnosis, plasma carnitine fractions and management in a further patient. Eur J Pediatr. 1993; 152: 433–436.CrossRefGoogle Scholar
20Hagenfeldt, L, von Döbeln, U, Holme, E, Alm, J, Brandberg, G, Enocksson, E, Lindeberg, L. 3-Hydroxydicarboxylic aciduria – a fatty acid oxidation defect with severe prognosis. J Pediatr. 1990; 116: 387–392.CrossRefGoogle ScholarPubMed
21Jackson, S, Bartlett, K, Land, J, Moxon, ER, Pollitt, RJ, Leonard, JV, Turnbull, DM. Long-chain 3-Hydoxyacyl-CoA dehydrogenase deficiency. Pediatr Res. 1991; 29: 406–411.CrossRefGoogle Scholar
22Wanders, RJA, Ijlst, L, Poggi, F, Bonnefont, JP, Munnich, A, Brivet, M, Rabier, D, Saudubray, JM. Human trifunctional protein deficiency: a new disorder of mitochondrial fatty acid B-oxidation. Biochem Biophys Res Commun. 1992; 188: 1139–1145.CrossRefGoogle Scholar
23Abrahamsson, K, Mellander, M, Eriksson, BO, Holme, E, Jodal, U, Jönsson, A, Lindstedt, S. Transient reduction of human left ventricular mass in carnitine depletion induced by antibiotics containing pivalic acid. Br Heart J. 1995; 74: 656–659.CrossRefGoogle ScholarPubMed
24Saltin, B: Oxygen transport during exercise: Role of the cardiovascular system. In: Williams, RS and Wallace, AG, ed. Biological Effects of Physical Activity. Champaign Illinois; 1989: 3–24.Google Scholar