The role of ATP and lactic acid for mitochondrial function during myocardial ischemia

Kahles, H.; Gebhard, Martha-Maria; Mezger, Viktor; Nordbeck, H.; Preusse, C. J.; Spieckermann, P. G.

doi:10.1007/bf01907503

Cited by 9 publications

(3 citation statements)

References 22 publications

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“…Light-microscopically these enlarged spaces appear like vacuoles (2,8). Fibers in these areas were shown biochemicaUy to contain dissociated lactic acid (33). Moreover, hypoxidosis can cause the transverse striation to disappear.…”

Section: Discussionmentioning

confidence: 97%

The myocardium and its pathological state during the perinatal period and infancy

1983

Basic Res Cardiol

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Summary311 hearts of fetuses, of premature and neonate babies, of preschool and school children were examined, irrespective of basic disease and cause of death. 63 hearts did not show any pathological alterations. They served as a control group. The fibers of 27 hearts of fetuses, premature and mature neonate babies were homogeneous" The close packing as well as the reduced number of myofibrils in some regions of the heart did not correspond to hearts of the same age and size of the control group.The following changes were found individually or in combination within the remaining 200 hearts:Perinuclear vacuoles and acidophilic fibers, acidophilic necroses, scars with or without calcification, interstitial haemorrhages, parietal thrombi, endocarditis and myocarditis.Prominent characteristics are perinuclear vacuoles, acidophilic fibers and acidophilic necroses. This combination often shows a characteristic morphological pattern: inner layer with acidophilic necroses, middle layer with acidophilia, and outer layer consisting of fibers with perinuclear vacuoles. This combination and the trilaminar arrangement lead to the conclusion that they may be caused by hypoxaemia, isehemia or hypoxidosis. Vacuoles and acidophilia are most likely to be reversible.According to their frequency, they appear to correlate with certain diseases (table 3), but none of the changes are specific for a certain disease:Perinuclear vacuoles, acidophilic fibers and acidophilic necroses very often exist with pulmonary diseases, with general infections and erythroblastosis. Interstitial haemorrhages and parietal thrombi can be traced in increasing numbers in traumas showing disseminated intravascular coagulation.Hypertrophic fibers are frequent in congenital heart disease, mostly in combination with acidophilic fibers and especially with scars.Further studies should aim at establishing a correlation between morphological and clinical observations. This paper suggests further studies in the field of morphology examining equivalent surgical material with the electron microscope.

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Section: Discussionmentioning

confidence: 97%

The myocardium and its pathological state during the perinatal period and infancy

1983

Basic Res Cardiol

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“…In addition, after ISO-induced ischemia-like injury, glycolysis in cardiomyocytes was significantly enhanced, gene expression of metabolic enzymes was upregulated, and the content of lactate was significantly increased, which could lead to cellular acidosis. In this case, H + is pumped out of the cell and Ca 2+ is pumped in, causing intracellular Ca 2+ overload and exacerbating myocardial damage [ 3 , 24 ]. Under the protection of bilobalide, the glycolysis in cardiomyocytes was significantly weakened, gene expression of related metabolic enzymes was downregulated and accumulation of lactate significantly decreased.…”

Section: Discussionmentioning

confidence: 99%

Impaired tricarboxylic acid cycle flux and mitochondrial aerobic respiration during isoproterenol induced myocardial ischemia is rescued by bilobalide

Wang

Zhang

Liu

et al. 2021

Journal of Pharmaceutical Analysis

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There is an urgent need to elucidate the pathogenesis of myocardial ischemia (MI) and potential drug treatments. Here, the anti-MI mechanism and material basis of Ginkgo biloba L. extract (GBE) were studied from the perspective of energy metabolism flux regulation. Metabolic flux analysis (MFA) was performed to investigate energy metabolism flux disorder and the regulatory nodes of GBE components in isoproterenol (ISO)-induced ischemia-like cardiomyocytes. It showed that [U– 13 C] glucose derived m+2 isotopologues from the upstream tricarboxylic acid (TCA) cycle metabolites were markedly accumulated in ISO-injured cardiomyocytes, but the opposite was seen for the downstream metabolites, while their total cellular concentrations were increased. This indicates a blockage of carbon flow from glycolysis and enhanced anaplerosis from other carbon sources. A Seahorse test was used to screen for GBE components with regulatory effects on mitochondrial aerobic respiratory dysfunction. It showed that bilobalide protected against impaired mitochondrial aerobic respiration. MFA also showed that bilobalide significantly modulated the TCA cycle flux, reduced abnormal metabolite accumulation, and balanced the demand of different carbon sources. Western blotting and PCR analysis showed that bilobalide decreased the enhanced expression of key metabolic enzymes in injured cells. Bilobalide's efficacy was verified by in vivo experiments in rats. This is the first report to show that bilobalide, the active ingredient of GBE, protects against MI by rescuing impaired TCA cycle flux. This provides a new mechanism and potential drug treatment for MI. It also shows the potential of MFA/Seahorse combination as a powerful strategy for pharmacological research on herbal medicine.

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“…This pathological condition is another consequence of oxygen (14) deficit and ischemia (18). It thus adds to the severe consequences of the oxygen deficiency.…”

Section: Functional Findings With Mpgmentioning

confidence: 99%

Uncoupler- and hypoxia-induced damage in the working rat heart and its treatment

1985

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In the working rat heart we investigated heart function (aortic and coronary flow) during a normoxic, a hypoxic, and a reoxygenation phase after hypoxia. A depressed heart function was obtained by limiting oxygen supply and reducing left ventricular filling pressure (preload). After hypoxic perfusion for about 90 min, reoxygenation resulted in a 50% decrease of aortic flow. Lactate production and release increased immediately after oxygen deprivation and reached a maximum after about 35 min of hypoxia. Following reoxygenation, lactate release decreased. Lactate dehydrogenase became significant after reoxygenation. After stabilization of aortic flow at 50% in the reoxygenation phase different reagents were examined for their influence on heart performance. 1.5 mM of 2-Mercaptopropionylglycine (MPG) significantly increased aortic flow by 40%. The oxidized form of MPG (ox-MPG) at a concentration of 0.6 mM increased aortic flow by 125%. A molecular mechanism is proposed involving reorientation of the ATPase molecules at their membrane sites.

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The role of ATP and lactic acid for mitochondrial function during myocardial ischemia

Cited by 9 publications

References 22 publications

The myocardium and its pathological state during the perinatal period and infancy

The myocardium and its pathological state during the perinatal period and infancy

Impaired tricarboxylic acid cycle flux and mitochondrial aerobic respiration during isoproterenol induced myocardial ischemia is rescued by bilobalide

Uncoupler- and hypoxia-induced damage in the working rat heart and its treatment

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