A Moderate Carnitine Deficiency Exacerbates Isoproterenol-Induced Myocardial Injury in Rats

Giudice, Pietro; Bonomini, Mario; Arduini, Arduino

doi:10.1007/s10557-016-6647-4

Cited by 12 publications

(8 citation statements)

References 53 publications

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“…Similar findings were obtained in murine models of moderate carnitine deficiency induced with carnitine depleting agents such as pivalic acid, mildronate and d-carnitine [77][78][79]. We have shown that rats exposed to a moderate reduction in cardiac l-carnitine content are more susceptible to myocardial injury induced by β-adrenergic stimulation (isoproterenol) along with an unanticipated high mortality rate [77]. When carnitine deficiency was corrected by supplementing the pivalate-treated rats with l-carnitine, the observed detrimental effects of isoproterenol were negligible along with no mortality.…”

Section: Metabolic Features Of L-carnitine Relevant To Pd Therapysupporting

confidence: 82%

The osmo-metabolic approach: a novel and tantalizing glucose-sparing strategy in peritoneal dialysis

et al. 2020

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Peritoneal dialysis (PD) is a viable but under-prescribed treatment for uremic patients. Concerns about its use include the bio-incompatibility of PD fluids, due to their potential for altering the functional and anatomical integrity of the peritoneal membrane. Many of these effects are thought to be due to the high glucose content of these solutions, with attendant issues of products generated during heat treatment of glucose-containing solutions. Moreover, excessive intraperitoneal absorption of glucose from the dialysate has many potential systemic metabolic effects. This article reviews the efforts to develop alternative PD solutions that obviate some of these side effects, through the replacement of part of their glucose content with other osmolytes which are at least as efficient in removing fluids as glucose, but less impactful on patient metabolism. In particular, we will summarize clinical studies on the use of alternative osmotic ingredients that are commercially available (icodextrin and amino acids) and preclinical studies on alternative solutions under development (taurine, polyglycerol, carnitine and xylitol). In addition to the expected benefit of a glucose-sparing approach, we describe an 'osmo-metabolic' approach in formulating novel PD solutions, in which there is the possibility of exploiting the pharmaco-metabolic properties of some of the osmolytes to attenuate the systemic side effects due to glucose. This approach has the potential to ameliorate pre-existing co-morbidities, including insulin resistance and type-2 diabetes, which have a high prevalence in the dialysis population, including in PD patients.

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Section: Metabolic Features Of L-carnitine Relevant To Pd Therapysupporting

confidence: 82%

The osmo-metabolic approach: a novel and tantalizing glucose-sparing strategy in peritoneal dialysis

et al. 2020

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“…Micronutrients are auxiliary, but essential, for the myocardium to utilize energy substrate, and thereby maintain normal structure and function. Thus, correction of these deficits can improve cardiac function . Sequentially, micronutrient supplementation for HF improves the energy utilization efficiency in the myocardium and restores cell function.…”

Section: Metabolic Alterations In the Failing Heartmentioning

confidence: 99%

“…Thus, correction of these deficits can improve cardiac function. [24][25][26] Sequentially, micronutrient supplementation for HF improves the energy uti-lization efficiency in the myocardium and restores cell function. Ayer et al and DiNicolantonio et al found that when HF patients received megadoses of coenzyme Q10, their LV ejection fraction and New York Heart Association (NYHA) class improved significantly.…”

Section: Micronutrientsmentioning

confidence: 99%

The Modulating Effects of Cardiac Resynchronization Therapy on Myocardial Metabolism in Heart Failure

Chen

et al. 2016

Pacing Clinical Electrophis

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Heart failure (HF) is associated with changes in cardiac substrate utilization and energy metabolism, including a decline in high-energy phosphate content, mitochondrial dysfunction, and phosphotransfer enzyme deficiency. A shift toward glucose metabolism was noted in the end stage of HF in animals, although HF in humans may not be associated with a shift toward predominant glucose utilization. Deficiencies of micronutrients are well-established causes of cardiomyopathy. Correction of these deficits can improve heart function. The genes governing the energy metabolism were predominantly under-expressed in nonischemic cardiomyopathy and hypertrophic cardiomyopathy but were overexpressed in ischemic cardiomyopathy. Cardiac resynchronization therapy (CRT) has been proven to increase cardiac efficiency without increasing myocardial oxygen consumption. Altered myocardial metabolism is normalized by CRT to improve ventricular function.

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“…Paraventricular hypothalamic adrenergic neurotransmission forms part of the pre-autonomic control of systemic cardiovascular function (Xu et al, 2012 ; Lee et al, 2013 ; Patel et al, 2016 ). Furthermore, abnormalities in the expression of β-adrenergic receptors (β AR) or its hyperactivation in cardiac tissue have been described in rodent models of heart failure (Madamanchi, 2007 ; Giudice et al, 2016 ; Yamazaki et al, 2016 ).…”

Section: Introductionmentioning

confidence: 99%

Systemic Sympathoexcitation Was Associated with Paraventricular Hypothalamic Phosphorylation of Synaptic CaMKIIα and MAPK/ErK

et al. 2017

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Systemic administration of adrenergic agonist (Isoproterenol; ISOP) is known to facilitate cardiovascular changes associated with heart failure through an upregulation of cardiac toll-like receptor 4 (TLR4). Furthermore, previous studies have shown that cardiac tissue-specific deletion of TLR4 protects the heart against such damage. Since the autonomic regulation of systemic cardiovascular function originates from pre-autonomic sympathetic centers in the brain, it is unclear how a systemically driven sympathetic change may affect the pre-autonomic paraventricular hypothalamic nuclei (PVN) TLR4 expression. Here, we examined how change in PVN TLR4 was associated with alterations in the neurochemical cytoarchitecture of the PVN in systemic adrenergic activation. After 48 h of intraperitoneal 150 mg/kg ISOP treatment, there was a change in PVN CaMKIIα and MAPK/ErK expression, and an increase in TLR4 in expression. This was seen as an increase in p-MAPK/ErK, and a decrease in synaptic CaMKIIα expression in the PVN (p < 0.01) of ISOP treated mice. Furthermore, there was an upregulation of vesicular glutamate transporter (VGLUT 2; p < 0.01) and a decreased expression of GABA in the PVN of Isoproterenol (ISOP) treated WT mice (p < 0.01). However, after a PVN-specific knockdown of TLR4, the effect of systemic administration of ISOP was attenuated, as indicated by a decrease in p-MAPK/ErK (p < 0.01) and upregulation of CaMKIIα (p < 0.05). Additionally, loss of inhibitory function was averted while VGLUT2 expression decreased when compared with the ISOP treated wild type mice and the control. Taken together, the outcome of this study showed that systemic adrenergic activation may alter the expression, and phosphorylation of preautonomic MAPK/ErK and CaMKIIα downstream of TLR4. As such, by outlining the roles of these kinases in synaptic function, we have identified the significance of neural TLR4 in the progression, and attenuation of synaptic changes in the pre-autonomic sympathetic centers.

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A Moderate Carnitine Deficiency Exacerbates Isoproterenol-Induced Myocardial Injury in Rats

Abstract: Our study suggests that carnitine deficiency exposes the heart to a greater risk of injury when sympathetic nerve activity is greatly stimulated, for example during emotional, mental or physical stress.

Cited by 12 publications

References 53 publications

The osmo-metabolic approach: a novel and tantalizing glucose-sparing strategy in peritoneal dialysis

The osmo-metabolic approach: a novel and tantalizing glucose-sparing strategy in peritoneal dialysis

The Modulating Effects of Cardiac Resynchronization Therapy on Myocardial Metabolism in Heart Failure

Systemic Sympathoexcitation Was Associated with Paraventricular Hypothalamic Phosphorylation of Synaptic CaMKIIα and MAPK/ErK

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