Myocardial carnitine transport

Siliprandi, N.; Ciman, M.; Sartorelli, L.

doi:10.1007/978-3-662-08390-1_7

Cited by 11 publications

(12 citation statements)

References 21 publications

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“…It has been reported that dietary supplementation of ¿-carnitine reverses the uraemic defect of Na,K pump function [28]. This is of particular interest, as carnitine deficiency is associated with altered lipid metabolism [29], and these changes could be of critical importance in the pathophysiology of uraemia.…”

Section: Discussionmentioning

confidence: 99%

Effects of Dialysis and Transplantation on Red Cell Na Pump Function in Renal Failure

Fervenza

Hendry

Ellory

1989

Nephron

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Ion pumping by the erythrocyte Na, K-ATPase has been measured using ouabain-sensitive ⁸⁶Rb flux in 11 non-dialysed patients with chronic renal failure (CRF), 13 patients on haemodialysis (HD), 13 patients on peritoneal dialysis (CAPD) and 15 patients with functional transplants (FT). Flux measurements were performed in plasma and simultaneous estimates of specific ³H-ouabain binding were made. The results indicate that, compared to normal controls, NaK pump flux was reduced by 21% in CRF (p < 0.01), 30% in HD (p < 0.01), 15% in CAPD (p < 0.02), and was normal in FT. Mean specific ouabain binding sites per cell ( ± SEM) were; controls 366 ± 16; CRF, 290 ± 16; HD, 344 ± 17; CAPD, 321 ± 18; FT, 345 ± 26. Calculation of mean turnover rate per pump site indicated that patients on HD showed a 30% reduction compared to controls (influx 55 K ions/s versus 79 K ions/s, p < 0.01). Cross-incubation experiments suggest that the lowered pump flux seen in the CRF and HD groups was due to plasma factors. This work shows that erythrocyte NaK pump number is reduced in CRF, while patients on maintenance HD have normal pump numbers per erythrocyte but reduced pump turnover.

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Section: Discussionmentioning

confidence: 99%

Effects of Dialysis and Transplantation on Red Cell Na Pump Function in Renal Failure

Fervenza

Hendry

Ellory

1989

Nephron

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“…In mammals, L-carnitine is synthesized in liver, brain, and (in humans) kidneys and is released into the circulatory system. The remaining organs are missing the hydroxylase which catalyzes the final conversion from deoxycarnitine to L-carnitine [42,43]. Heart tissues do not synthesize L-carnitine but can generate deoxycarnitine, which can subsequently be exchanged for L-carnitine from the blood stream [42,44].…”

Section: Plos Onementioning

confidence: 99%

Serum untargeted metabolomic changes in response to diet intervention in dogs with preclinical myxomatous mitral valve disease

Li¹,

Laflamme²,

Bauer

2020

PLoS ONE

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Myocardial energy deprivation plays a causal role in the development of heart failure. A cardiac protection blend (CPB) of nutrients including medium chain triglycerides, fish oil and other key nutrients was developed to slow the progression of canine myxomatous mitral valve disease (MMVD). A six-month dietary intervention demonstrated efficacy of CPB in slowing MMVD progression. Untargeted metabolomic analysis of serum from these dogs identified 102 differential metabolites (adjusted P < 0.05). The ratios of omega-6 to omega-3 fatty acid (FA) changed from 2.41 and 1.46 in control and CPB groups at baseline to 4.30 and 0.46 at 6 months respectively. A 2.7-fold increase of α-aminobutyrate, a myocardial modulator of glutathione homeostasis, was found in CPB dogs compared to 1.3-fold increase in control dogs. Arginine and citrulline, precursors of nitric oxide biosynthesis, were both increased 2-fold; caprate, a medium chain FA, was increased 3-fold; and deoxycarnitine, precursor of carnitine biosynthesis, was increased 2.5-fold in CPB dogs. Margarate and methylpalmitate decreased in response to CPB, a potential benefit in MMVD dogs as positive correlations were found between changes in both these FAs and left atrial diameter (r = 0.69, r = 0.87 respectively, adjusted P < 0.05). Sphingomyelins with very long chain saturated FAs associated with decreased risk of heart failure in humans were increased in MMVD dogs fed the CPB diet. Our data supports the hypothesis that CPB improves FA utilization and energetics, reduces oxidative stress and inflammation in MMVD dogs. More studies are needed to understand the roles of specific metabolites in MMVD.

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“…Carnitine and its acyl derivatives (acetyl and propionyl) are naturally occurring substances that are required for the transport of long-chain acyl groups derived from fatty acids across mitochondrial membranes, a necessary preliminary to fatty acid oxidation and hence ATP production [1,2]. For this reason it has been proposed that they may protect ischemic tissues, particularly the myocardium [3,4], by prolonging this oxidative metabolism.…”

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confidence: 99%

Short-term hemodynamic effects of intravenous propionyl-L-carnitine in anesthetized dogs

Cevese

Schena

Cerutti

1991

Cardiovasc Drug Ther

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The effects of intravenous administration of propionyl-L-carnitine (PLC) were investigated in anesthetized dogs instrumented for the analysis of general hemodynamic and electrocardiographic data, peripheral blood flows, coronary blood flow and oxygen consumption, urine flow, and renal function. PLC was administered in bolus (20, 60, and 200 mg/kg) or by infusion (20 mg/kg/min * 15 min or 30 mg/kg/min * 10 min). In some cases also L-carnitine (LC) and L-carnitine+propionate (LC + P) were administered in doses equimolar to those of PLC. PLC elicited dose-dependent, short-lasting enhancements of cardiac output, both in open- and closed-chest conditions. Arterial blood pressure, heart rate, and contractility varied slightly and unpredictably; the substance did not elicit electrocardiographic effects. These responses were not changed by alpha- or beta-adrenergic blockade, nor by the administration of a calcium antagonist, but they were abolished or reversed by the combination of such blocking interventions. Mesenteric and iliac blood flows were increased by both PLC and LC; LC + P increased these, and in addition increased renal blood flow. A strong diuresis obtained with PLC, LC, and LC + P was due to osmotic clearance following the administration of hyperosmotic solutions. PLC elicited coronary vasodilation with reduced oxygen extraction; this effect lasted longer than the general hemodynamic effects and was not seen with LC. All the cardiovascular actions of PLC can be attributed to its pharmacologic properties, rather than to its role as a metabolic intermediate.

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Myocardial carnitine transport

Cited by 11 publications

References 21 publications

Effects of Dialysis and Transplantation on Red Cell Na Pump Function in Renal Failure

Effects of Dialysis and Transplantation on Red Cell Na Pump Function in Renal Failure

Serum untargeted metabolomic changes in response to diet intervention in dogs with preclinical myxomatous mitral valve disease

Short-term hemodynamic effects of intravenous propionyl-L-carnitine in anesthetized dogs

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