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  • 1
    Electronic Resource
    Electronic Resource
    Effectiveness of nicorandil in the preservation of myocardium stressed by transient ischemia and its influence on cardiac metabolism during coronary artery occlusion with subsequent reperfusion: a comparison with isosorbide dinitrate (1985)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 329 (1985), S. 440-446 
    Details
    ISSN: 1432-1912
    Keywords: Cardiac metabolism ; Ischemia ; Isosorbide dinitrate ; Nicorandil ; Oxygen-debt ; Oxygen-repayment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary This study was designed to investigate the effects of nicorandil in comparison to isosorbide dinitrate (ISDN) on hemodynamics, on myocardial metabolism and on effectiveness in the preservation of ischemically stressed myocardium. Repeated ischemia (3 min) was produced in anaesthetized open-chest mongrel dogs by proximal, intermittent left anterior descending artery occlusion with subsequent reperfusion. In each experiment 2–3 control occlusions were compared to 2–3 occlusions under nicorandil or ISDN. Application of both nicorandil (0.64 μmol·kg−1 body weight, i.v.) and ISDN (1.27 μmol·kg−1 body weight, i.v.) led to a significant afterload reduction and to a decrease of the coronary vascular resistance. The efficiency of the compounds in the protection of ischemic myocardium was examined by quantification of oxygen-debt and oxygen-repayment in the occlusion and reperfusion periods. Compared to control, premedication with nicorandil led to a significant increase of oxygen-debt, whereas ISDN reduced it significantly. Oxygen-repayment remained unchanged. The influence of the drugs on the metabolism of glucose, lactate and free fatty acids (FFA) was examined under basic conditions, in ischemia and during reperfusion. For all substrates, extraction, extraction ratio and oxygen extraction ratio were calculated. Under basic conditions, glucose metabolism was significantly enhanced in both groups but FFA metabolism was inhibited only by ISDN. In ischemia, FFA metabolism was enhanced by nicorandil and depressed by ISDN. Data obtained in this study suggest that nicorandil may even aggravate the metabolic and energetic situation of ischemic myocardium and, on the other hand, clearly support the well documented protective effects of ISDN.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00496379
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    Paper (German National Licenses)
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  • 2
    Electronic Resource
    Electronic Resource
    Changes in myocardial substrate utilisation and protection of ischemic stressed myocardium by oxfenicine [(S)-4-hydroxyphenylglycine] (1984)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 327 (1984), S. 70-74 
    Details
    ISSN: 1432-1912
    Keywords: Cardiac metabolism ; Myocardial ischemia ; Oxfenicine ; Oxygen debt ; Oxygen repayment ; Release of electrolytes and substrates
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Potential protective effects of oxfenicine [(S)-4-hydroxyphenylglycine] in ischemic stressed canine myocardium have been studied. This compound is characterized as a drug leading to metabolic inhibition of free fatty acid (FFA) metabolism. The drug (0.06 mmol·kg−1 body weight) caused no changes in hemodynamics or energy demand (Et) but depressed myocardial oxygen consumption (MVO2) by 11% (P〈0.02). Significant changes in FFA and lactate metabolism were observed: lactate extraction (EX) increased from 22.5–37.1 μmol/min, extraction ratio (EXR) from 16.5–30% and oxygen extraction ratio (OER) from 24.8–38%; EX of FFA decreased from 6900–5000 nmol/min, EXR from 48.2–31.4% and OER from 59.7–46.6%. Arterial concentrations of FFA and lactate remained unchanged. EX, EXR and OER of glucose were not affected under basic conditions. In the same collective, repeated ischemia (3 min) was produced by proximal occlusion of the left anterior descending artery (LAD). The efficiency of the drug was examined by (a) the amounts of ischemia metabolites released in the early reperfusion and (b) quantification of O2-debt and O2-repayment in the occlusion- and reperfusion periods. Compared to control occlusions, premedication led to a reduced O2-debt (P〈0.01) combined with a reduced amount of oxygen additionally taken up in the early reperfusion (P〈0.05). Furthermore, release of potassium increased (+7.1%; P〈0.05); release of lactate (-32%, P〈0.001) and inorganic phosphate (-34%, P〈0.01) decreased. These data give support to the concept that a pharmacologically induced shift of cardiac metabolism with reduction of FFA utilisation may be favourable in circumstances with limited oxygen supply.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00504994
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    Paper (German National Licenses)
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  • 3
    Electronic Resource
    Electronic Resource
    Neonatal pyruvate dehydrogenase deficiency with lipoate responsive lactic acidaemia and hyperammonaemia (1989)
    Springer
    European journal of pediatrics 148 (1989), S. 543-547 
    Details
    ISSN: 1432-1076
    Keywords: Pyruvate dehydrogenase deficiency ; Hyperammonaemia ; Peritoneal dialysis ; Lipoic acid ; Plasma amino acids
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A 2-day-old girl developed a severe lactic acidosis with a normal lactate/pyruvate ratio and hyperammonaemia. Plasma arginine and citrulline levels were below the limit of detection. In muscle total pyruvate dehydrogenase complex (PDHC) and pyruvate decarboxylase (E1) activities were reduced to a fraction of lower control values. The acute neonatal period was bridged with peritoneal dialysis, dichloroacetate therapy, supplements of arginine and branched chain amino acids, a complete vitamin B complex and lipoic acid. Lactate homeostasis responded to pharmacological supplements of lipoic acid. At age 1 year the child was hypotonic, showed severe developmental retardation, optic atrophy and cranial dysmorphism. She died aged 1 year 8 months with signs of respiratory paralysis but with normal lactate levels under assisted breathing. Pathological findings at autopsy were suggestive of Leigh syndrome, interstitial pneumonia and extensive fatty infiltration of hepatocytes. Regression analysis of data from 187 plasma amino acid determinations from the patient over a period of 1 year 8 months revealed a persistent imbalance involving alanine, glutamic acid, glutamine, proline, citrulline and branched chain amino acids. Aspects of acute and long-term therapy in this patient and some implications of the imbalances in plasma amino acids are discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00441554
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    Paper (German National Licenses)
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