Improvement of myocardial function in diabetic rats after treatment with L-carnitine

Paulson, Dennis J.; Schmidt, Mary J.; Traxler, John; Ramacci, M. T.; Shug, Austin L.

doi:10.1016/0026-0495(84)90199-9

Cited by 68 publications

(33 citation statements)

References 39 publications

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“…This has deleterious consequences for the integrity of the mitochondrial inner membrane, even though an obvious relationship between gross overall tissue long-chain acyl-CoA levels and tissue damage may not be able to be discerned experimentally [81,82]. The consequences of this sequence of events is well illustrated in experimental low-flow ischaemia [83]. Importantly, upon reperfusion of ischaemic rat hearts, AMP content and AMPK activity remain elevated for a considerable time [72], such that heart mitochondrial CPTo would be anticipated to continue to generate acylcarnitines and thus intramitochondrial long-chain acyl-CoA [84].…”

Section: Cardiac Musclementioning

confidence: 99%

The malonyl-CoA–long-chain acyl-CoA axis in the maintenance of mammalian cell function

Zammit

1999

Biochemical Journal

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Long-chain acyl-CoA esters have potent specific actions (e.g. on gene transcription, membrane trafficking) as well as non-specific ones (e.g. on phospholipid bilayers). They are synthesized on the cytosolic aspects of several intracellular membranes, to give rise to (a) cytosolic pool(s) to which a variety of enzymes and processes have access, including some localized in the nucleus. Their concentration in cells is highly regulated, interconversion with corresponding acylcarnitines being the most important mechanism involved. This reaction is catalysed by cytosol-accessible carnitine long-chain acyl (palmitoyl) transferase activities that are themselves located on multiple membrane systems. Regulation of these activities is through the inhibitory action of malonyl-CoA. Hence the existence of a potent malonyl-CoA-acyl-CoA axis through which many processes involved in the maintenance of mammalian cell function are regulated. The molecular, topographical and physiological interactions that make this possible are described and discussed.

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Section: Cardiac Musclementioning

confidence: 99%

The malonyl-CoA–long-chain acyl-CoA axis in the maintenance of mammalian cell function

Zammit

1999

Biochemical Journal

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“…In control hearts, these parameters of cardiac function were unchanged after carnitine treatment even though total carnitine stores were markedly increased. Liedtke et al 63 have suggested that acute L-carnitine administration beneficially affects cardiac function by decreasing use of fatty acids; this decrease leads to energy sparing processes noted in both aerobic and ischemic myocardium. Rodis et al, 66 using a perfused rat heart system, demonstrated that carnitine in the perfusate depressed palmitate uptake and slightly decreased fatty acid oxidation in aerobic muscle.…”

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confidence: 99%

“…These hearts were then less vulnerable to ischemia, leading to improved function. 63 Liedtke et al 6465 have shown protective effects of L-carnitine treatment against experimentally induced myocardial ischemia. These studies, with the knowledge that myocardial stores are reduced in cardiomyopathic hamsters, 24 " 2 ' led to the present carnitine-treatment study.…”

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confidence: 99%

L-carnitine treatment improves cardiac performance and restores high-energy phosphate pools in cardiomyopathic Syrian hamster.

Whitmer

1987

Circulation Research

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Hamsters with either the dilated (BIO 53.58) or hypertrophic (BIO 14.6) form of cardiomyopathy and an inbred control strain of hamster (FIB) were treated for 6 months with high-dose L-carnitine (1 g/kg/day i.p.). After treatment, the animals were killed and their hearts perfused by the isolated working technique. Mechanical performance (as indicated by the double product of heart rate and left ventricular [LV] peak systolic pressure) of both carnitine-treated cardiomyopathic groups was increased significantly above their respective sham-treated groups. Associated with these increases in mechanical performance were significant increases in both peak-positive LV dP/dt (index of contractility) and peak negative dP/dt (index of relaxation) in both carnitine-treated myopathic groups. Serum carnitine levels were increased 10-15 times within 2 hours after injection of L-carnitine in all 3 groups. Myocardial free-carnitine levels were increased twofold in both control and dilated myopathic hearts above their respective sham-treated groups, restoring the level in the dilated hearts comparable to those of controls. Myocardial carnitine levels in the hypertrophic group were not significantly affected by treatment. Total high-energy phosphate stores, i.e., ATP plus creatine phosphate, were restored to control levels by L-carnitine treatment in both cardiomyopathic groups. Levels of the breakdown products of ATP were maintained primarily in the more readily convertible adenosine diphosphate and adenosine monophosphate forms in all three treated groups. These changes resulted in significantly higher ratios of (ATP)/(ADP + AMP + adenosine) and (creatine phosphate)/ (creatine) in the treated hearts. This is the first study demonstrating that high-dose L-carnitine treatment results in improved cardiac performance and increased myocardial total high-energy phosphate stores in the Syrian hamster model with one of two distinct forms of cardiomyopathy, i.e., dilated or hypertrophic. The mechanisms for these effects of exogenous L-carnitine treatment cannot be totally explained by changes in oxidative energy metabolism. (Circulation Research 1987; 61:396-408)

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“…Diabetes in animals and humans leads to deterioration of carnitine and lipid metabolism [8][9][10][11][12][20][21][22][23]. It is well known that streptozotocin-induced diabetic rats develop myocardial carnitine deficiency [7,8,[10][11][12]. In several studies, decreased carnitine concentrations in both plasma and myocardium in diabetic animals have been observed [7,10].…”

Section: Discussionmentioning

confidence: 95%

“…Decreased levels of carnitine in cardiac tissue may impair myocardial function, since it has been shown that carnitine deficiency can produce cardiomyopathy [18,19]. Diabetes in animals and humans leads to deterioration of carnitine and lipid metabolism [8][9][10][11][12][20][21][22][23]. It is well known that streptozotocin-induced diabetic rats develop myocardial carnitine deficiency [7,8,[10][11][12].…”

Section: Discussionmentioning

confidence: 99%

Myocardial and Hepatic Free Carnitine Concentrations in Pups of Diabetic Female Rats

Akısü

Kültürsay²,

Çoker³

et al. 2002

Ann Nutr Metab

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Background/Aims: Adequate carnitine levels are required for normal fatty acid and energy metabolism in heart muscle. It is well known that streptozotocin-induced diabetic rats develop myocardial carnitine deficiency and that carnitine therapy may be beneficial to the diabetic heart. Infants of diabetic mothers (IDM) are known to be at risk for developing a hypertrophic type of cardiomyopathy. In the present investigation, we examined the free carnitine concentration from cardiac and hepatic tissue in pups of streptozotocin-induced diabetic female rats. We also assessed the effect of maternal L-carnitine supplementation on the free carnitine concentration in pups of diabetic rats. Method: Three groups, each consisting of 4 Wistar albino female rats, were studied, Group 1 (untreated diabetic; n = 4) and group 2 (L-carnitine-treated diabetic; n = 4) rats were given streptozotocin (60 mg/kg) by intraperitoneal injection; group 3 were controls. During pregnancy, L-carnitine was given at a dose of 150 mg/kg by intraperitoneal injection once a day for 14 days. Cesarean section was carried out, and 113 newborn rats (group 1 n = 36; group 2 n = 38; group 3 n = 39) were obtained from all the pregnant rats. Results: The free carnitine concentration in myocardial tissue was significantly decreased in the female diabetic rats (p < 0.001). However, the free carnitine concentration from hepatic tissue in diabetic female rats was similar to that in controls. In pups of group 1 diabetic rats, a significantly decreased free carnitine concentration was found in both myocardial and hepatic tissue compared to group 2 and controls. The free carnitine content from myocardial and hepatic tissue was significantly elevated in the maternal L-carnitine-supplemented group when compared to group 1 and control pups (p < 0.001 and p < 0.05, respectively). Conclusions: The present study has demonstrated that the free carnitine concentration from myocardial and hepatic tissue is significantly reduced in pups of streptozotocin-induced diabetic female rats. This study has also shown that administration of maternal L-carnitine improves the carnitine level in pups of diabetic rats. A decreased myocardial carnitine concentration may be partly responsible for the development of cardiomyopathy in IDM.

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Improvement of myocardial function in diabetic rats after treatment with L-carnitine

Cited by 68 publications

References 39 publications

The malonyl-CoA–long-chain acyl-CoA axis in the maintenance of mammalian cell function

The malonyl-CoA–long-chain acyl-CoA axis in the maintenance of mammalian cell function

L-carnitine treatment improves cardiac performance and restores high-energy phosphate pools in cardiomyopathic Syrian hamster.

Myocardial and Hepatic Free Carnitine Concentrations in Pups of Diabetic Female Rats

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