Improvement of Myocardial Fatty Acid Metabolism through <i>L</i>-Carnitine Administration to Chronic Hemodialysis Patients

Abstract

The concentration of carnitine, which is essential to fatty acid metabolism, can decrease markedly in patients on long-term hemodialysis coincident with life-threatening cardiac damage. However, administration of L-carnitine improves the myocardial function of these patients. To evaluate the underlying events of this phenomenon, we used recently developed technology, ¹²³I-labeled β-methyl-p-iodophenyl-pentadecanoic acid (BMIPP) myocardial scintigraphy, as a test of myocardial fatty acid metabolism. Our results showed that the free carnitine concentration (19.2 ± 6.5 μmol/l) was lower in 11 chronically dialyzed patients than in 8 healthy controls (49.3 ± 7.7 μmol/l, p < 0.0001). Additionally the heart to mediastinal ratio (H/M) of BMIPP was higher for these patients than for the controls (1.91 ± 0.19 vs. 1.52 ± 0.24, p < 0.005), and the patients’ washout rate (WOR) of BMIPP was lower (17.2 ± 6.0 vs. 22.8 ± 4.2%, p < 0.05). After L-carnitine was administered orally to the patients at doses of 1 g/day for 1 month and 0.5 g/day for the following month, the concentration of free carnitine in their sera increased to 85.4 ± 27.0 μmol/l (p < 0.0001). Although the H/M ratio did not change (1.89 ± 0.20) with this treatment, their WOR increased to 21.9 ± 6.6% (p < 0.001), similar to that of controls. The left ventricular end-diastolic dimension and left ventricular fractional shortening remained unchanged, as shown by echocardiography. The results presented here denote that a carnitine deficiency in chronically hemodialyzed patients disrupts their myocardial fatty acid metabolism, which is improved by L-carnitine supplementation.

L-Carnitine Supplementation Decreases the Left Ventricular Mass in Patients Undergoing Hemodialysis

“…As in a previous study, 11 echocardiography revealed no improvement in myocardial contractility. However, this technique may not detect moderate deficiencies of carnitine in terms of myocardial contractility when patients chronically treated with HD are at rest.…”

“…We found previously that myocardial washout of 123-I labeled -methyl-p-iodophenyl-pentadecanoic acid (BMIPP), a fatty acid analogue used to examine myocardial metabolism, decreased in patients on long-term HD and was restored by L-carnitine supplementation. 11 The washout of BMIPP from the heart also decreased after a disturbance of mitochondrial carnitine acyltransferase 1 by tetradecylglycidic acid (TDGA) administration. 26 Litwin et al reported that administration of TDGA induced LVH with storage of lipids in rat hearts.…”

“…18 The normal values used here for these levels were as cited in a previous report. 11 Echocardiography was conducted immediately before the midweek HD session to minimize any influence of the patient's hydration state both at the beginning and end of the study. Echocardiography was prepared using an SSD-2200 system (Aloka, Tokyo, Japan).…”

“…10 We previously reported that L-carnitine administration ameliorated myocardial fatty acid metabolism in patients undergoing HD. 11 There were also reports of improvement of cardiac dysfunction by L-carnitine supplementation, especially in patients with declined cardiac systolic function or with symptoms of heart failure; [12][13][14][15] however, when patients with normal myocardial function were studied, no benefit of carnitine was seen. 13,16 Left ventricular hypertrophy (LVH) is common and is an independent predictor of cardiac death in patients undergoing dialysis.…”

Mekanik Ventilatördeki Tavşanlarda Propofol İnfüzyonu İle Oluşan Metabolik ve Biokimyasal Değişikliklerde L-Karnitin Tedavisinin Etkileri

“…Karnitinin kalp yetersizliği olan hastalarda egzersiz kapasitesini ve maksimum oksijen tüketimini arttır-mak, halsizliği azaltmak, kas fonksiyonlarını iyileştirmek gibi yararları vardır (6,42,43). İlave olarak karnitinin kronik hemodiyaliz hastalarında miyokard yağ asidi metabolizmasını ve buna bağlı bozulmuş kardiyak fonksiyonları, kardiyak aritmileri düzelttiği gösterilmiştir (6,(44)(45)(46).…”