Improvement of Ischemic Myocardial Dysfunction by Nisoldipine in Relation to Its Coronary Vasodilating Action

Trimarchi, Giuseppe; Arcadi, Francesca Antonia; Luca, Roberto De; Imperatore, C.; Santoro, Giuseppe; Trimarchi, Fabio; Costa, Giovanni

doi:10.1254/jjp.62.215

Cited by 11 publications

(4 citation statements)

References 42 publications

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“…In Langendorff-perfused rat hearts, FDP was shown to preserve high-energy metabolites during anoxia, restore myocardial metabolism and contractility during reperfusion (9), and improve myocardial efficiency under well-perfused and well-oxygenated conditions (22). Improvement in tissue metabolic state during metabolic stress has been reported in a number of other tissue types, including kidney (1), liver (19), brain (26), erythrocytes (8), smooth muscle (5), and intestine (24). Many of these effects were likely due to FDP entering cells, but also due to the known calcium chelating activity of FDP (see Ref.…”

Section: Discussionmentioning

confidence: 98%

Myocardial metabolism of exogenous FDP is consistent with transport by a dicarboxylate transporter

Hardin

Lazzarino

Tavazzi

et al. 2001

American Journal of Physiology-Heart and Circulatory Physiology

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The extent to and the mechanism by which fructose-1,6-bisphosphate (FDP) crosses cell membranes are unknown. We hypothesized that its transport is either via band 3 or a dicarboxylate transporter. The question was addressed in isolated Langendorff rat hearts perfused under normoxic conditions. Groups of hearts received the following metabolic substrates (in mM): 5 FDP; 5 FDP + either 5, 10, or 20 fumarate; 10 FDP and either 5, 10, or 20 fumarate; or 5 FDP + 2 4,4'-dinitrostilbene-2,2'-disulfonate (DNDS), a band 3 inhibitor. FDP uptake and metabolism were measured as production of [(13)C]lactate from [(13)C]FDP or (14)CO(2) and [(14)C]lactate from uniformly labeled [(14)C]FDP in sample perfusates. During 30 min of perfusion, FDP metabolism was 12.4 +/- 2.6 and 31.2 +/- 3.0 micromol for 5 and 10 mM FDP, respectively. Addition of 20 mM fumarate reduced FDP metabolism over a 30-min perfusion period to 3.1 +/- 0.6 and 6.3 +/- 0.5 micromol for 5 and 10 mM FDP groups, respectively. DNDS did not affect FDP utilization. These data are consistent with transport of FDP by a dicarboxylate transport system.

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Section: Discussionmentioning

confidence: 98%

Myocardial metabolism of exogenous FDP is consistent with transport by a dicarboxylate transporter

Hardin

Lazzarino

Tavazzi

et al. 2001

American Journal of Physiology-Heart and Circulatory Physiology

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“…During the past twenty years of brain research post-ischemic outcome improvements by FBP have been found by some to be dramatic, by others to be simply modest[6,11,12,19-21,31,35,39], and by a smaller number to be completely nonexistent[10,22,23]. FBP studies showing neuroprotection pose a formidable intellectual challenge: do improved outcomes come from important, already known injurious mechanisms that are typically focused upon, such as glutamate excitotoxicity, calcium overload, acidosis, oxygen radicals, PARP-1 activation, apoptosis, etc?…”

Section: Discussionmentioning

confidence: 99%

“…Ischemic neuroprotection from FBP administration was subsequently demonstrated in animal experiments[6,12,21,35], cell culture studies[11,19,20,31,39], as well as in a brain slice study by us[3]. Our previous investigation of FBP neuroprotection used 31 P and 1 H ex vivo NMR spectroscopy in a horizontal 4.7 Tesla wide-bore spectrometer.…”

Section: Introductionmentioning

confidence: 99%

Fructose-1,6-bisphosphate does not preserve ATP in hypoxic–ischemic neonatal cerebrocortical slices

2008

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Fructose-1,6-bisphosphate (FBP), an endogenous intracellular metabolite in glycolysis, was found in many preclinical studies to be neuroprotective during hypoxia-ischemia (HI) when administered exogenously. We looked for HI neuroprotection from FBP in a neonatal rat brain slice model, using 14.1 Tesla 1 H / 31 P/ 13 C NMR spectroscopy of perchloric acid slice extracts to ask: 1) if FBP preserves high energy phosphates during HI; and 2) if exogenous [1-13 C]FBP enters cells and is glycolytically metabolized to [3-13 C]lactate. We also asked: 3) if substantial superoxide production occurs during and after HI, thinking such might be treatable by exogenous FBP's antioxidant effects. Superfused P7 rat cerebrocortical slices (350μm) were treated with 2 mM FBP before and during 30 min of HI, and then given four hours of recovery with an FBP-free oxygenated superfusate. Slices were removed before HI, at the end of HI, and at 1 and 4 hours after HI. FBP did not improve high energy phosphate levels or change 1 H metabolite profiles. Large increases in [3-13 C]lactate were seen with 13 C NMR, but the lactate fractional enrichment was always (1.1±0.5)%, implying that all of lactate's 13 C was natural abundance 13 C, that none was from metabolism of 13 C-FBP. FBP had no effect on the fluorescence of ethidium produced from superoxide oxidation of hydroethidine. Compared to control slices, ethidium fluorescence was 25% higher during HI and 50% higher at the end of recovery. Exogenous FBP did not provide protection or enter glycolysis. Its use as an antioxidant might be worth studying at higher FBP concentrations.

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“…During the twenty years that followed his initial FBP experiments, many others, too many to report, studied FBP use in hypoxia, ischemia, and/or oxidative stress. Post-ischemic outcome improvements were found by some to be dramatic, by others to be simply modest [38–40], and by a smaller number to be completely nonexistent [41–43]. Although many important, significant, animal investigations of FBP’s protective and therapeutic actions have been carried out since the 1980’s, and although much has also been learned about molecular mechanisms of hypoxic/ischemic injury, the mechanisms by which FBP protects various tissues were never clearly established, and FBP administration never became part of routine clinical care.…”

Section: Investigations Of Two Metabolites As Treatments In Oxidatmentioning

confidence: 99%

Metabolomics of Oxidative Stress in Recent Studies of Endogenous and Exogenously Administered Intermediate Metabolites

Liu

Litt

Segal

et al. 2011

IJMS

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Aerobic metabolism occurs in a background of oxygen radicals and reactive oxygen species (ROS) that originate from the incomplete reduction of molecular oxygen in electron transfer reactions. The essential role of aerobic metabolism, the generation and consumption of ATP and other high energy phosphates, sustains a balance of approximately 3000 essential human metabolites that serve not only as nutrients, but also as antioxidants, neurotransmitters, osmolytes, and participants in ligand-based and other cellular signaling. In hypoxia, ischemia, and oxidative stress, where pathological circumstances cause oxygen radicals to form at a rate greater than is possible for their consumption, changes in the composition of metabolite ensembles, or metabolomes, can be associated with physiological changes. Metabolomics and metabonomics are a scientific disciplines that focuse on quantifying dynamic metabolome responses, using multivariate analytical approaches derived from methods within genomics, a discipline that consolidated innovative analysis techniques for situations where the number of biomarkers (metabolites in our case) greatly exceeds the number of subjects. This review focuses on the behavior of cytosolic, mitochondrial, and redox metabolites in ameliorating or exacerbating oxidative stress. After reviewing work regarding a small number of metabolites—pyruvate, ethyl pyruvate, and fructose-1,6-bisphosphate—whose exogenous administration was found to ameliorate oxidative stress, a subsequent section reviews basic multivariate statistical methods common in metabolomics research, and their application in human and preclinical studies emphasizing oxidative stress. Particular attention is paid to new NMR spectroscopy methods in metabolomics and metabonomics. Because complex relationships connect oxidative stress to so many physiological processes, studies from different disciplines were reviewed. All, however, shared the common goal of ultimately developing “omics”-based, diagnostic tests to help influence therapies.

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Improvement of Ischemic Myocardial Dysfunction by Nisoldipine in Relation to Its Coronary Vasodilating Action

Cited by 11 publications

References 42 publications

Myocardial metabolism of exogenous FDP is consistent with transport by a dicarboxylate transporter

Myocardial metabolism of exogenous FDP is consistent with transport by a dicarboxylate transporter

Fructose-1,6-bisphosphate does not preserve ATP in hypoxic–ischemic neonatal cerebrocortical slices

Metabolomics of Oxidative Stress in Recent Studies of Endogenous and Exogenously Administered Intermediate Metabolites

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