Developmental changes in energy substrate use by the heart

Lopaschuk, Gary D.; Collins-Nakai, Ruth L.; Itoi, Toshiyuki

doi:10.1093/cvr/26.12.1172

Cited by 281 publications

(200 citation statements)

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“…Possibly, neonatal cardiomyocytes respond differently to changes in glucose concentration than postmitotic adult cardiac cells. This hypothesis is supported by the changes in substrate metabolism that occur during the perinatal period, when cardiomyocytes shift from predominant nonoxidative glucose utilization to predominant fatty acid oxidation (35). Alternatively, the protective effect of glucose may be limited to apoptotic pathways other than the one induced by palmitic acid.…”

Section: Discussionmentioning

confidence: 98%

Glucose and Palmitic Acid Induce Degeneration of Myofibrils and Modulate Apoptosis in Rat Adult Cardiomyocytes

Dyntar

Eppenberger‐Eberhardt

et al. 2001

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Several studies support the concept of a diabetic cardiomyopathy in the absence of discernible coronary artery disease, although its mechanism remains poorly understood. We investigated the role of glucose and palmitic acid on cardiomyocyte apoptosis and on the organization of the contractile apparatus. Exposure of adult rat cardiomyocytes for 18 h to palmitic acid (0.25 and 0.5 mmol/l) resulted in a significant increase of apoptotic cells, whereas increasing glucose concentration to 33.3 mmol/l for up to 8 days had no influence on the apoptosis rate. However, both palmitic acid and elevated glucose concentration alone or in combination had a dramatic destructive effect on the myofibrillar apparatus. The membrane-permeable C 2 -ceramide but not the metabolically inactive C 2 -dihydroceramide enhanced apoptosis of cardiomyocytes by 50%, accompanied by detrimental effects on the myofibrils. The palmitic acid-induced effects were impaired by fumonisin B1, an inhibitor of ceramide synthase. Sphingomyelinase, which activates the catabolic pathway of ceramide by metabolizing sphingomyeline to ceramide, did not adversely affect cardiomyocytes. Palmitic acidinduced apoptosis was accompanied by release of cytochrome c from the mitochondria. Aminoguanidine did not prevent glucose-induced myofibrillar degeneration, suggesting that formation of nitric oxide and/or advanced glycation end products play no major role. Taken together, these results suggest that in adult rat cardiac cells, palmitic acid induces apoptosis via de novo ceramide formation and activation of the apoptotic mitochondrial pathway. Conversely, glucose has no influence on adult cardiomyocyte apoptosis. However, both cell nutrients promote degeneration of myofibrils. Thus, gluco-and lipotoxicity may play a central role in the development of diabetic cardiomyopathy. Diabetes 50: 2105

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Section: Discussionmentioning

confidence: 98%

Glucose and Palmitic Acid Induce Degeneration of Myofibrils and Modulate Apoptosis in Rat Adult Cardiomyocytes

Dyntar

Eppenberger‐Eberhardt

et al. 2001

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“…We used, in this study, heparin for anti-coagulation and obtained blood samples www.intechopen.com under heprinized state because of two reasons; 1) for preservation of veins and arteries from obstruction in younger children and 2) for our aim of studying myocardial metabolism in patients under critical states as in pediatric intensive care unit or in surgical intervention where many patients were heparinized. In spite of these limitation, this method we applied here is still useful for clinical study on myocardial metabolism (Vánky et al 2006) because data obtained are supposed not far from animal model study (Lopaschuk et al, 1992), computer simulation study and isotopical study in human.…”

Section: Characteristics Of Methodology On Myocardial Energy Metabolimentioning

confidence: 99%

“…The very variable glucose uptake shown in other reports including adults suggested that glucose may not play an important role for myocardial energy supply for children at rest. (Vánky et al 2006,Lopaschuk et al, 1992. It has been demonstrated that adult hypertrophied hearts prefer to oxidize glucose.…”

Section: Myocardial Use Of Lactate and Other Substrates In Non-cyanotmentioning

confidence: 99%

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Myocardial Lactate Metabolism in Children with Non-Cyanotic Congenital Heart Disease

Itoi¹

2012

Congenital Heart Disease - Selected Aspects

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“…Rate pressure product increased with heart rate and was found to relate to myocardial oxygen consumption (r = 0.75), which increased maximally by 47 ± 9% due to increases in coronary blood flow. Phosphocreatine/ATP ratio decreased significantly, and calculated ADP increased between baseline and peak perMajor modifications in myocardial energy metabolism and regulation occur shortly after birth (1,2). ATP production is tightly coupled to utilization in the newborn myocardium as well as the mature myocardium.…”

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confidence: 99%

Myocardial Energy Metabolism in the Newborn Lamb In Vivo during Pacing-Induced Changes in Oxygen Consumption

Portman

Xue

1995

Pediatr Res

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Myocardial energy metabolism was studied in newborn sheep to determine whether the metabolic responses to pacing-induced increases in heart rate were similar to those previously found during catecholamine stimulation. Open-chest newborn sheep, 3 to 9 d old (n = 11), underwent atrial pacing at a respiratory rate harmonic just above the intrinsic heart rate. Pacing rate was increased by 30 beats/min every 5 min until conduction block or a drop in systemic arterial pressure occurred. Phosphorous metabolites were monitored simultaneously (n = 7) using a 31p magnetic resonance surface coil over the heart within a magnet operating at 4.7 tesla. Myocardial oxygen consumption was monitored via an extracorporeal shunt from the coronary sinus. Rate pressure product increased with heart rate and was found to relate to myocardial oxygen consumption (r = 0.75), which increased maximally by 47 ± 9% due to increases in coronary blood flow. Phosphocreatine/ATP ratio decreased significantly, and calculated ADP increased between baseline and peak perMajor modifications in myocardial energy metabolism and regulation occur shortly after birth (1, 2). ATP production is tightly coupled to utilization in the newborn myocardium as well as the mature myocardium. However, epinephrineinduced increases in cardiac oxygen consumption and work rates in the newborn in situ are associated with corresponding changes in ATP hydrolysis products (1, 3). These high-energy phosphate alterations are not evident in the older animal. This finding would seem to indicate that the newborn myocardium, unlike the mature myocardium, uses these products, ADP and Pi' in a feedback or kinetic mode of respiratory control. Increasing cytosolic ADP and Pi would thereby stimulate mitochondrial oxidative phosphorylation. Alternatively, this relation between ADP, Pi' and oxygen consumption in the newborn may reflect developmental modifications in substrate utilization precipitated directly by exogenous catecholamines. formance but returned to near baseline levels during recovery at the initial pacing rate. These findings indicate that intracellular high-energy phosphate concentrations do change with alterations in myocardial oxygen consumption induced by cardiac pacing in the newborn. These changes are similar to those found during epinephrine infusion. Furthermore, the ATP hydrolysis products probably participate in myocardial respiratory regulation in the newborn in vivo. (Pediatr Res 37: 182-188, 1995) Abbreviations MVO z, myocardial oxygen consumption per, phosphocreatine NMR, nuclear magnetic resonance Pi' intracellular phosphate RPP, rate pressure product bpm, beats per minute NADH/NADtheoreticallyexistsinequilibriumwithphosphorylation potential, ATP/ADP'P i, and is influenced by reducing equivalent delivery or substrate supply (4). Studies performed both in perfused hearts (5) and in intact animals (6) indicate that phosphorylation potential can be altered through changes in substrate utilization without concomitant changes in oxygen consumption. Accordingly...

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Developmental changes in energy substrate use by the heart

Cited by 281 publications

References 0 publications

Glucose and Palmitic Acid Induce Degeneration of Myofibrils and Modulate Apoptosis in Rat Adult Cardiomyocytes

Glucose and Palmitic Acid Induce Degeneration of Myofibrils and Modulate Apoptosis in Rat Adult Cardiomyocytes

Myocardial Lactate Metabolism in Children with Non-Cyanotic Congenital Heart Disease

Myocardial Energy Metabolism in the Newborn Lamb In Vivo during Pacing-Induced Changes in Oxygen Consumption

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