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  • 1
    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
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  • 2
    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
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