Skip Navigation

European Journal of Heart Failure 2000 2(2):189-193; doi:10.1016/S1388-9842(00)00064-7
This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (8)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Gürlek, A.
Right arrow Articles by Oral, D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Gürlek, A.
Right arrow Articles by Oral, D.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© 2000 European Society of Cardiology

The effects of L-carnitine treatment on left ventricular function and erythrocyte superoxide dismutase activity in patients with ischemic cardiomyopathy

Adalet Gürleka,*, Eralp Tutara, Ethem Akçilb, Irem Dinçera, Çetin Erola, Pelin A. Kocatürkb and Dervis Orala

a Department of Cardiology, Ankara University Faculty of Medicine Ankara, Turkey
b Department of Pathophysiology, Ankara University Faculty of Medicine Ankara, Turkey

* Corresponding author. Birlik Mahallesi 11.sokak 24/15, Çankaya, Ankara, Turkey. Tel.: +90-312-3103333; fax: +90-312-3125251.


   Abstract
Top
 Abstract
1. Introduction
 2. Methods
 3. Results
 4. Discussion
 References
 
We studied the effects of L-carnitine on left ventricular systolic function and the erythrocyte superoxide dismutase activity in 51 patients with ischemic cardiomyopathy. They all previously were under the treatment of angiotensin-converting enzyme inhibitor, digitalis and diuretics. Patients were randomized into two groups. In group I (n = 31), 2 g/day L-carnitine was added to therapy. L-Carnitine was not given to the other 20 patients (Group II). In group I (mean age 64.3 ± 7.8 years), 27 of the patients were men, and four were women. In group II (mean age 66.2 ± 8.7 years), 17 of the patients were men, and three were women. Twenty age-matched healthy subjects (mean age: 60.1 ± 5.3 years) constituted the control group. In each group, left ventricular ejection fraction (LVEF) by echocardiography and red cell superoxide dismutase activity by spectrophotometric method were measured initially and after 1 month of randomisation. Compared with normal healthy subjects (n = 20), patients (n = 51) had significantly higher red cell SOD activity (5633 ± 1225 vs. 3202 ± 373 U/g Hb, P < 0.001). At the end of 1 month of L-carnitine therapy, red cell SOD activity showed an increase in group I (5918 ± 1448 to 7218 ± 1917 U/g Hb, P < 0.05). In group II, red cell SOD activity showed no significant change after 1 month of randomisation (5190 ± 545 to 5234 ± 487 U/g Hb, P = 0.256). One month after randomisation there was a significant increase in LVEF in both groups I and II (37.8–42.3%, P < 0.001 in group I; 41.5–43.8%, P < 0.001 in group II). The improvement in LVEF was more significant in the L-carnitine group (4.5% vs. 2.3%, P < 0.01). We conclude that, as a sign of increased free radical production, superoxide dismutase activity was further increased in patients with L-carnitine treatment. L-Carnitine treatment in combination with other traditional pharmacological therapy might have an additive effect for the improvement of left ventricular function in ischemic cardiomyopathy.

Key Words: Ischemic cardiomyopathy • L-Carnitine • Erythrocyte superoxide dismutase

Received September 23, 1999; Revised January 17, 2000; Accepted February 16, 2000


   1. Introduction
Top
 Abstract
 1. Introduction
2. Methods
 3. Results
 4. Discussion
 References
 
Carnitine is a naturally occurring compound in the body, and is synthesised chiefly by the liver. Tissues with active fatty acid metabolism, such as skeletal muscle and the heart, contain the highest levels of carnitine but are incapable of synthesising it [1,2]. Fatty acid metabolism constitutes one of the main sources of energy and, more specifically, is the preferential substrate for cardiac oxidative metabolism. Carnitine is an essential factor in transporting the long-chain fatty acids (acyl CoA) from the cytoplasm into the mitochondria where the beta-oxidation takes place [1–3].

A reduced O2 supply, which occurs in the course of hypoxia or ischemia, causes the slowing down of intramitochondrial oxidative processes and thus of beta-oxidation, leading to the accumulation of the intermediate products of oxidative metabolism, particularly acyl CoA [3,4]. Accumulated acyl CoA is capable of inhibiting adenine nucleotide translocase, the enzyme responsible for transporting ATP from the mitochondria, where it is produced, to the cytoplasm, where it is utilised for muscle contraction. [3–5]. In ischemic conditions, then, there is an overall slowing down in the mitochondrial energy production mechanism [4–6]

L-Carnitine, an essential intermediate compound in the physiological transport of long-chain fatty acids across the mitochondrial membrane has been found to be below normal levels in the ischemic myocardium. Experimental and clinical studies have shown that in the ischemic, infarcted or failing myocardium, carnitine depletion occurs rapidly [4,7–9]. The exogenous administration of L-carnitine restores normal levels of intramyocardial carnitine and has been shown to be capable of improving the mitochondrial function of ischemic cells [7]. It reduces the ischemia-induced increase in long-chain fatty acid concentration and thus lessens its deleterious functional effects [10–12]. The mechanism by which carnitine exerts its action in ischemic metabolism lies in its ability to react with the acyl CoA which accumulates as a result of the slowing down of beta-oxidation, and, in turn, is capable of carrying acyl groups out of the anoxic cell [4,13]. The anti-ischemic and antianginal effects of L-carnitine have been shown by the improvement in myocardial metabolism observed during atrial pacing in patients with coronary artery disease and in exercise tolerance in patients with chronic stable angina [14].

Orlando at al. have shown that with oral L-carnitine treatment in patients with chronic cardiac ischemia there has been an improvement in symptoms, functional NYHA class and in the left ventricle shortening fraction [9].

On the basis of these clinical trials we decided to study the effects of oral L-carnitine administration in patients with ischemic cardiomyopathy.


   2. Methods
Top
 Abstract
 1. Introduction
 2. Methods
3. Results
 4. Discussion
 References
 
2.1. Patient population
Fifty-one patients with the diagnosis of ischemic cardiomyopathy were studied. Patients having one or more of the diseases such as chronic inflammatory disease, symptomatic peripheral vascular disease, diabetes mellitus, infection, respiratory disease or malignancy were excluded.

All patients were previously under the treatment of angiotensin-converting enzyme inhibitor, digitalis and diuretics. The present investigation was an unblinded study. Patients were randomized into two groups on a 3:2 basis. In group I (n=31) 2 g/day oral L-carnitine was added to therapy. L-Carnitine was not given to the other 20 patients (Group II). In group I, 27 of the patients were men, and four were women. Nineteen of them had previous history of anterior wall myocardial infarction, 10 had previous history of inferior wall myocardial infarction and the other two had a history of anterior and inferior wall myocardial infarction. The mean age of the patients was 64.3±7.8 years. In group II, 17 of the patients were men, and three were women. Seven of them had previous history of anterior wall myocardial infarction, eight had previous history of inferior wall myocardial infarction and the other five had a history of anterior and inferior wall myocardial infarction. The mean age of the patients was 66.2±8.7 years (Table 1). Twenty age-matched healthy subjects (mean age: 60.1±5.3 years) constituted the control group. In the study group, 43 of the patients had had coronary angiography previously in which 14 of them also had percutaneous transluminal coronary angioplasty and eight of them had coronary artery bypass surgery.


View this table:
[in this window]
[in a new window]

  		Table 1 Basal clinical data in patients

 
2.2. Echocardiography
All patients underwent a complete physical examination with measurement of blood pressure and heart rate, standard 12-lead ECG at rest and two-dimensional M-mode standard echocardiography. Ejection fractions were calculated from orthogonal apical two-chamber and four-chamber views with biplane area–length method for three cardiac cycles and averaged. In both group of patients, the ejection fraction of the left ventricle was measured by echocardiography initially and also after 1 month of randomisation.

2.3. Red cell superoxide dismutase activity
The blood samples of both the controls and the patients were drawn in the morning, always at the same time. The 5-ml blood samples were taken from fasting subjects with polyethylene disposable syringes and put into a demineralised centrifuge tube, which contained heparin. The plasma and red cells of each sample were separated by centrifugation. The blood samples for Cu–Zn–SOD determination were studied immediately. The red cell SOD activity was determined according to Winterbourn’s method by spectrophotometer [15].

2.4. Statistical analysis
Student’s two-tailed t-test for paired samples was used to compare the differences in left ventricular ejection fraction and red cell SOD activity before and after 1 month of randomisation. Red cell SOD activity was compared between patients and normal healthy subjects by unpaired Student’s t-test. Non-parametric Mann–Whitney U-test was used to compare a percent increase in ejection fractions between groups I and II. The data were expressed as mean±S.D. A P-value<0.05 was considered to be significant.


   3. Results
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
4. Discussion
 References
 
There were no side effects observed in patients during 1 month of follow-up. At the end of 30 days of randomisation, the left ventricle ejection fraction showed a significant improvement in the L-carnitine group (37.8 to 42.3%, P<0.001). The ejection fraction remained unvaried in one patient. In two-thirds of the patients, the improvement in EF was over 10% and two of them showed a 30% increase. There was no decrease in EF in any patients. In group II the improvement in EF was also significant (41.5 to 43.8%, P<0.001) (Table 2). The mean percent increase in EF was 12.5±8.3% in the L-carnitine group and 6.1±4.3% in group II (P<0.01).


View this table:
[in this window]
[in a new window]

  		Table 2 Clinical data 1 month after randomisation

 
Compared with normal healthy subjects (n=20), patients (n=51) had significantly higher red cell SOD activity (5633±1225 vs. 3202±373 U/g Hb, P<0.001). At the end of 1 month of L-carnitine therapy, red cell SOD activity showed a significant increase in group I (5918±1448 to 7218±1917 U/g Hb, P<0.05). In group II red cell SOD activity showed no significant change after 1 month of randomisation (5190±545 to 5234±487 U/g Hb, P=0.256) (Table 2).


   4. Discussion
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
References
 
Except the carnitine deficiency syndromes, carnitine’s use in heart diseases remains equivocal [16–18]. The rationale for the use of L-carnitine in patients with ischemic heart disease initially originated from the finding that myocardial carnitine concentrations were lower in these patients [7,8]. Depressed myocardial uptake of 123-β-methyl iodophenyl pentadecanoic acid, which may reflect depressed fatty acid catabolism in viable myocardium, is frequently observed in patients with ischemic heart disease. Watanabe at al. have shown that 3 months of oral L-carnitine treatment increased the depressed 123-β-methyl iodophenyl pentadecanoic acid uptake and improved myocardial ischemia [19]. In the study of Fujiwara at al. it was shown that intravenously administered L-carnitine stimulated cardiac metabolism and increased coronary blood flow during exercise in patients with ischemic heart disease [20]. Beyond this, there is increasing evidence suggesting a beneficial effect for carnitine therapy in a number of cardiovascular disorders including angina pectoris, acute ischemia, congestive heart failure, and also hyperlipidemia [2,4,7,9,14,18,20–23].

It was shown that there is a role of oxygen free radicals in the pathogenesis of post-ischemic myocardial dysfunction (myocardial ‘stunning’, reperfusion injury) after acute myocardial infarction [24–26]. Free radicals could also be implicated in the development and progression of chronic myocardial dysfunction. Underlying coronary artery disease may predispose to stunning. Repeated episodes of stunning may lead to permanent myocardial dysfunction [27,28]. Additional factors could also favour free radical generation in congestive heart failure. Pressure or volume overloads may lead the protracted cycles of generalised myocardial ischemia and reperfusion and thus the generation of oxygen free radicals [29,30]. Adrenergic activity is increased in congestive heart failure. Catecholamines may augment free radical generation by increasing mitochondrial respiration and undergoing auto-oxidation [31,32]. Free radicals cause impairment of myocyte metabolism and contraction and also cause endothelial dysfunction and induce arrhythmias [33–35]. Both lipid peroxidation and thiol group oxidation can cause these derangements as a pathological process. In the study of Diaz-Velez et al., plasma malondialdehyde levels, a marker of lipid peroxidation, were found to be abnormally elevated in patients with chronic heart failure and were strongly associated with the chronicity of the heart failure state [36].

Several lines of evidence show that administration of SOD, a free radical scavenger, attenuates the free radicals induced by myocardial injury [37,38]. It was shown that propionyl-L-carnitine suppresses formation of hydroxyl radicals in an ischemia reperfusion model, and attenuates peroxidative injury [39]. The free radical scavenging properties of propionyl-L-carnitine haven’t been seen with L-carnitine [40,41]. In our study, echocardiographic improvement in patients under treatment with L-carnitine in addition to conventional therapy is more significant than patients under conventional treatment. In our study, compared with normal healthy subjects, in patients with ischemic cardiomyopathy, the red cell SOD activity was higher (P<0.001), and this might be attributable to enhanced oxygen free radical generation in failing heart. One month after L-carnitine therapy, we observed that there was a significant increase in red cell SOD activity. This increase in red cell SOD activity after L-carnitine treatment may be attributable to enhanced β-oxidation of fatty acids, and so on increased free radical generation. This may suggests a negative effect of L-carnitine in the energy metabolism of the failing heart. Otherwise, the increase in SOD activity with L-carnitine treatment seems to be the result of an increase in free radical generation, which already has been enhanced in the failing heart.

Angiotensin-converting enzyme inhibitors have been shown to cause a reduction in oxygen free radical production [42]. In group II, patients were under treatment of ACE inhibitor, diuretics and digitalis and the red cell SOD activity showed no significant change after 1 month of randomisation (5190±545 to 5234±487 U/g Hb, P=0.256).

A more widely recognised salutary action of L-carnitine is its ability to reduce the accumulation of long-chain acyl CoA in the ischemic mitochondrial matrix [8,10–12,43]. This accumulation is thought to be partially responsible for the loss of myocardial contractility. Additionally, L-carnitine has been reported to improve pyruvate metabolism, to reduce lactate production and acidosis [8,12]. Despite some ambiguity regarding the mechanism, oral L-carnitine has been shown to improve global left ventricle performance in patients with ischemic cardiomyopathy [4,21,44,45]. The available short-term controlled studies in patients with stable coronary artery disease indicate that L-carnitine improves exercise tolerance and increases the ischemic threshold. Cherchi et al. have shown that L-carnitine administered to patients with stable angina pectoris has increased the exercise test tolerance on the cycle ergometer and has reduced S-T segment depression at maximum load [46]. In the study of Taillard et al., in patients with dilated cardiomyopathy dramatic improvement of the cardiac function was assessed by radionuclide methods during oral L-carnitine therapy [45]. A recent multicenter investigation of patients with anterior myocardial infarctions (CEDIM trial) has shown attenuation in left ventricular enlargement with L-carnitine therapy [7].

In the study of Ghidini et al., elderly subjects suffering from heart failure, secondary to ischemic and/or hypertensive heart disease, were given oral L-carnitine for 45 days in addition to traditional therapy. A distinct improvement was observed in patients with respect to their functional status [23].

It is concluded that exogenous administration of L-carnitine can restore adequate intramyocardial carnitine levels and reduce the deleterious effects of accumulated long chain fatty acids but, furthermore, increase in erythrocyte SOD activity as a sign of increased oxidative stress in patients with ischemic cardiomyopathy. Because of the short-term follow-up and the small number of patients, our findings may be limited to make a powerful interpretation about the role of L-carnitine treatment in ischemic cardiomyopathy. However, the improvement in left ventricular global performance may suggests that it can be a useful therapeutic agent in combination with traditional pharmacological therapy for the treatment of patients with heart failure and ischemic heart disease.


   References
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
 References
 

  1. Pierpont M.E., Judd D., Goldenberg I., Ring W.S., Olivari M.T., Pierpont G.L. Myocardial carnitine in end stage congestive heart failure. Am J Cardiol (1989) 64:56–60.[CrossRef][Web of Science][Medline]
  2. Arsenian M.A. Carnitine and its derivatives in cardiovascular disease. Prog Cardiovasc Dis (1997) 40:265–286.[CrossRef][Web of Science][Medline]
  3. Di Lisa F., Barbato R., Manebo R., Siliprandi N. Carnitine and carnitine esters in mitochondrial metabolism and function. In: The carnitine system. A new therapeutical approach to cardiovascular diseases—De Jong J.W., Ferrari R., eds. (1995) Dordrecht: Kluwer Academic Publishers. 21–38.
  4. Kobayashi A., Masumura Y., Yamazaki N. L-Carnitine treatment for congestive heart failure — experimental and clinical study. Jpn Circ J (1992) 56:86–94.[Medline]
  5. McHowat J., Yamada K.A., Saffitz J.F., Corr P.B. Subcellular distribution of endogenous long-chain acyl carnitines during hypoxia in adult canine myocytes. Cardiovasc Res (1993) 27:1237–1243.[Abstract/Free Full Text]
  6. Yamada K.A., McHowat J., Yan Gx., et al. Cellular uncoupling induced by accumulation of long chain acylcarnitine during ischemia. Circ Res (1994) 74:83–95.[Abstract/Free Full Text]
  7. Iliceto S., Scrutinio D., Bruzzi P., et al. Effects of L-carnitine administration on left ventricular remodelling after acute anterior myocardial infarction: the L-Carnitine Ecocardiografia Digitalizzata Infarto Miocardico (CEDIM) Trial. J Am Coll Cardiol (1995) 26:380–387.[Abstract]
  8. Chierchia S.L., Fragasso C. Metabolic management of ischaemic heart disease. Eur Heart J (1993) 14(Suppl_G):2–5.[Abstract/Free Full Text]
  9. Orlando G., Rusconi C. Oral L-carnitine in the treatment of chronic cardiac ischemia in elderly patients. Clin Trials J (1986) 23:338–344.[Web of Science]
  10. Liedtke A.J., Nellis S.H., Whitesell L.F. Effects of carnitine isomers on fatty acid metabolism in ischemic swine hearts. Circ Res (1981) 48:859–866.[Free Full Text]
  11. Shug A.L., Thomsen J.H., Folts J.D., et al. Changes in tissue levels of carnitine and other metabolites during myocardial ischemia and anoxia. Arch Biochem Biophys (1978) 187:25–33.[CrossRef][Web of Science][Medline]
  12. Suzuki Y., Kamikawa T., Kobayashi A., Masumura Y., Yamazaki N. Effects of L-carnitine on tissue levels of acyl carnitine, acyl coenzyme A and high energy phosphate in ischemic dog hearts. Jpn Circ J (1981) 45:687–694.[Medline]
  13. Kobayashi A., Fujisawa S. Effect of L-carnitine on mitochondrial acyl CoA esters in the ischemic dog heart. J Mol Cell Cardiol (1994) 26:499–508.[CrossRef][Web of Science][Medline]
  14. Thomsen J.H., Shug A.L., Yap V.U., Patel A.K., Karras T.J., DeFelice S.L. Improved pacing tolerance of the ischemic human myocardium after administration of carnitine. Am J Cardiol (1979) 43:300–306.[CrossRef][Web of Science][Medline]
  15. Winterbourn C.C., Hawkins R.E., Brain M. Red cell superoxide dismutase activity. J Lab Clin Med (1975) 85:337–350.[Web of Science][Medline]
  16. Vockley J. The changing face of disorders of fatty acid oxidation. Mayo Clin Proc (1994) 69:249–257.[Web of Science][Medline]
  17. Waber L., Valle D., Neill C., DiMauro S., Shug A. Carnitine deficiency presenting as familial cardiomyopathy: a treatable defect in carnitine transport. J Pediatrics (1982) 101:700–705.[CrossRef][Web of Science][Medline]
  18. Pepine C.J. The therapeutic potential of carnitine in cardiovascular disorders. Clin Ther (1991) 13:2–21.[Web of Science][Medline]
  19. Watanabe S., Ajisaka R., Edo K., Takeyasu N. Effects of L-carnitine on patients with ischemic heart disease evaluated by myocardial spect with 123-β-methyl iodophenyl pentadecanoic acid (BMIPP). J Nucl Cardiol (1995) 2:47.
  20. Fujiwana M., Nakano T., Tamoto S., Yamada Y. Effect of L-carnitine in patients with ischemic heart disease. J Cardiol (1991) 21:493–504.[Medline]
  21. Davini P., Bigalli A., Lamanna F. Controlled study on L-carnitine therapeutic efficacy in post-infarction. Drugs Exp Clin Res (1992) 18:355–365.[Web of Science][Medline]
  22. Sobobata I., Noda S., Hayashi H., Yokota M., Tsuzuki M. Clinical evaluation of the effect of levocarnitine chloride on exercise tolerance in stable angina pectoris by the serial multistage treadmill exercise testing: a multicenter, double-blind study. Jpn Clin Pharmacol Ther (1989) 20:607–618.
  23. Ghidini O., Azzurro M., Vita G., Sartori G. Evaluation of the therapeutic efficacy of L-carnitine in congestive heart failure. Int J Clin Pharmacol Ther Toxicol (1988) 26:217–220.[Medline]
  24. Alexis F.E., Renate R., Wolfgang K. Cardioprotection by superoxide dismutase: a catecholamine-dependent process? Anesth Analg (1993) 76:239–246.[Web of Science][Medline]
  25. Kloner R.A., Przyklenk K., Whittaker P. Deleterious effects of oxygen radicals in ischemia/reperfusion. Resolved and unresolved issues. Circulation (1989) 80:1115–1127.[Abstract/Free Full Text]
  26. Myers M.L., Bolli R., Lekich R.F., Hartley C.J., Roberts R. Enhancement of recovery of myocardial function by oxygen free-radical scavengers after reversible regional ischemia. Circulation (1985) 72:915–921.[Abstract/Free Full Text]
  27. McMurray J., Mc Lay J., Chopra M., Bridges A., Belch J.J.F. Evidence for enhanced radical activity in chronic congestive heart failure secondary to coronary artery disease. Am J Cardiol (1990) 15:1261–1262.
  28. McMurray J., Chopra M., Abdullah W., Smith E. Evidence of oxidative stress in chronic heart failure in humans. Eur Heart J (1993) 14:1493–1498.[Abstract/Free Full Text]
  29. Figueras J., Cinca J., Senador G., Rius J. Progressive mechanical impairment associated with progressive but reversible electrocardiographic ischaemic changes during repeated brief coronary artery occlusion in pigs. Cardiovasc Res (1986) 20:797–806.[Abstract/Free Full Text]
  30. Belch J.J.F., Bridges A.B., Scott N., Chopra M. Oxygen free radicals and congestive heart failure. Br Heart J (1991) 65:245–248.[Abstract/Free Full Text]
  31. Mc Cord J.M., Roy R.S., Schaffer S.W. Free radicals and myocardial ischemia: the role of xanthine oxidase. Adv Myocardiol (1985) 5:182–189.
  32. Freeman B.A., Crapo M.D. Biology of disease: free radicals and tissue injury. Lab Invest (1982) 47:412–426.[Web of Science][Medline]
  33. Scherer N.M., Deamer D.W. Oxidative stress impairs the functions of sarcoplasmic reticulum by oxidation of sulphydryl groups in the Ca+2 ATPase. Arch Biochem Biophys (1986) 246:589–601.[CrossRef][Web of Science][Medline]
  34. Goldhaber J.L., Ji S., Lamp S.T., Weiss J.N. Effects of exogenous free radicals on electromechanical function and metabolism in isolated rabbit and guinea and reperfusion injury. J Clin Invest (1989) 83:1800–1809.[Web of Science][Medline]
  35. Kim M., Akera T. Oxygen free radicals: cause of ischemia-reperfusion injury to cardiac Na+–K+-ATPase. Am J Physiol (1987) 252:252–257.
  36. Diaz-Velez C.R., Garcia-Castineiras S., Mendoza-Ramos E., Hernandez-Lopez E. Increased malondialdehyde in peripheral blood of patients with congestive heart failure. Am Heart J (1996) 131:146–152.[CrossRef][Web of Science][Medline]
  37. Ambrosio G., Beaker L.C., Hutchins G., Weisman H.F. Reduction in experimental enfact size by recombinant human superoxide dismutase: insights into the pathophysiology of reperfusion injury. Circulation (1986) 74:1424–1433.[Abstract/Free Full Text]
  38. Gross G.J., Farbwer N.E., Hardman H.F., Warltier H.F. Beneficial actions of superoxide dismutase and catalase in stunned myocardium. Am J Physiol (1986) 250:372–377.
  39. Packer L., Valenza M., Serbinova E., Starke-Reed P., Frost K., Kagan V. Free radical scavenging is involved in the protective effect of L-propionyl-carnitine against ischemia-reperfusion injury of the heart. Arch Biochem Biophys (1991) 288:533–537.[CrossRef][Web of Science][Medline]
  40. Reznick A.Z., Kagan V.E., Ramsey R., et al. Antiradical effects in L-propionyl carnitine protection of the heart against ischemia-reperfusion injury: the possible role of iron chelation. Arch Biochem Biophys (1992) 296:394–401.[CrossRef][Web of Science][Medline]
  41. Bertelli A., Conte A., Ronca G., Zucchi R. Effect of propionyl carnitine on cardiac energy metabolism evaluated by the release of purine catabolites. Drugs Exp Clin Res (1991) 17:115–118.[Web of Science][Medline]
  42. Pitt B. Regression of left ventricular hypertrophy in patients with hypertension: blockade of the renin–angiotensin–aldosterone system. Circulation (1998) 98:1987–1989.[Free Full Text]
  43. Kobayashi A., Suzuki Y., Kamikawa T., et al. Effects of L-carnitine on ventricular arrhythmias after coronary reperfusion. Jpn Circ J (1983) 47:536–542.[Medline]
  44. Schiavoni G., Pennestri F., Mongiando R., Mazzri M. Cardiodynamic effects of L-carnitine in ischemic cardiomyopathy. Drugs Exp Clin Res (1983) 9:171–186.[Web of Science]
  45. Taillard F., Mundler O., Tillous B.I., Desbois J.C., Paturneau J.M. Value of radionuclide assessment with thallium 201 scintography in carnitine deficiency cardiomyopathy. Eur Heart J (1988) 9:811–818.[Abstract/Free Full Text]
  46. Cherchi A., Lai C., Angelino F., et al. Effects of L-carnitine on exercise tolerance in chronic stable angina: a multicenter, double-blind, randomized, placebo controlled crossover study. Int J Clin Pharmacol Ther Toxicol (1985) 23:569–572.[Medline]

Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Am J EpidemiolHome page
G. Flores-Mateo, P. Carrillo-Santisteve, R. Elosua, E. Guallar, J. Marrugat, J. Bleys, and M.-I. Covas
Antioxidant Enzyme Activity and Coronary Heart Disease: Meta-analyses of Observational Studies
Am. J. Epidemiol., July 15, 2009; 170(2): 135 - 147.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (8)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Gürlek, A.
Right arrow Articles by Oral, D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Gürlek, A.
Right arrow Articles by Oral, D.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?