Postischemic recovery and oxidative stress are independent of nitric-oxide synthases modulation in isolated rat heart.
ABSTRACT During myocardial ischemia and reperfusion, nitric oxide ((.)NO) was shown to exert either beneficial or detrimental effects. Uncoupled (.)NO synthases (NOS) can generate superoxide anion under suboptimal concentrations of substrate and cofactors. The aim of our study was to investigate the role of NOS modulation on 1) the evolution of functional parameters and 2) the amount of free radicals released during an ischemia-reperfusion sequence. Isolated perfused rat hearts underwent 30 min of total ischemia, followed by 30 min of reperfusion in the presence of N(G)-nitro-D- or L-arginine methyl ester (NAME, 100 microM) or of D- or L-arginine (3 mM). Functional parameters were recorded and coronary effluents were analyzed with electron spin resonance to identify and quantify the amount of alpha-phenyl-N-tert-butylnitrone spin adducts produced during reperfusion. The antioxidant capacities of the compounds were determined with the oxygen radical absorbance capacity test. L-NAME-treated hearts showed a reduction of coronary flow and contractile performance, although neither L-NAME nor L-arginine improved the recovery of coronary flow, left end diastolic ventricular pressure, rate pressure product, and duration of reperfusion arrhythmia, compared with their D-specific enantiomers. A large and long-lasting release of alkyl/alkoxyl radicals was detected upon reperfusion, but no differences of free radical release were observed between D- and L-NAME or D- and L-arginine treatment. These results may indicate that, in our experimental conditions, cardiac NOS might not be a major factor implicated in the oxidative burst that follows a global myocardial ischemia.
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ABSTRACT: Circulation on blood extracorporeally through plastic tubing activates several pathways including systemic inflammation and oxidative stress. These phenomena are suspected to participate to neurological and cardiovascular side effects observed in the patients under cardiopulmonary bypass (CPB). A direct relationship, in diabetic patients, between hyperglycemia and morbidity and mortality has been established. However, it is still unclear whether perioperative hyperglycemia has a direct effect on adverse events in cardiac surgery. The purpose of this study was to determine the influence of hyperglycemia on inflammation and oxidative stress in patients under CPB during cardiac surgery.Annales De Cardiologie Et D Angeiologie - ANN CARDIOL ANGEIOL. 01/2008; 57(3):155-160.
Article: Forgotten Radicals in Biology.[show abstract] [hide abstract]
ABSTRACT: Redox reactions play key roles in intra- and inter-cellular signaling, and in adaptative processes of tissues towards stress. Among the major free radicals with essential functions in cells are reactive oxygen species (ROS) including superoxide anion (O2 (•-)), hydroxyl radical ((•)OH) and reactive nitrogen species (RNS) such as nitric oxide ((•)NO). In this article, we review the forgotten and new radicals with potential relevance to cardiovascular pathophysiology. Approximately 0.3% of O2 (•-) present in cytosol exists in its protonated form: hydroperoxyl radical (HO2 (•)). Water (H2O) can be split into two free radicals: (•)OH and hydrogen radical (H(•)). Several free radicals, including thiyl radicals (RS(•)) and nitrogen dioxide (NO2 (•)) are known to isomerize double bonds. In the omega-6 series of poly-unsaturated fatty acids (PUFAs), cis-trans isomerization of γ-linolenate and arachidonate catalyzed by RS(•) has been investigated. Evidence is emerging that hydrogen disulphide (H2S) is a signaling molecule in vivo which can be a source of free radicals. The Cu-Zn superoxide dismutase (SOD) enzyme can oxidize the ionized form of H2S to hydro-sulphide radical: HS(•). Recent studies suggest that H2S plays an important function in cardiovascular functions. Carbonate radical, which can be formed when (•)OH reacts with carbonate or bicarbonate ions, is also involved in the activity of Cu-Zn-SOD. Recently, it has been reported that carbonate anion were potentially relevant oxidants of nucleic acids in physiological environments. In conclusion, there is solid evidence supporting the formation of many free radicals by cells leading which may play an important role in their homeostasis.International journal of biomedical science : IJBS. 12/2008; 4(4):255-259.
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ABSTRACT: Heart transplant is considered to be an extremely severe ischemia-reperfusion sequence. Post-ischemic dysfunction triggers multiple processes especially oxidative stress, but the mechanisms remain unclear. Free radical interactions lead to peroxynitrite generation, which seems to be involved in early post-transplant heart failure. The aim of this study was to evaluate the potential impact of a peroxynitrite decomposition catalyst: FeTPPS (5,10,15,20-tetrakis-[4-sulfonatophenyl]-porphyrinato-fer[III]) and pyruvate on myocardial functional recovery after cardioplegic arrest using an experimental protocol in rat hearts. Isolated working rat hearts were subjected to ischemia (4 h at 4 degrees C in cardioplegic solutions), followed by 45 min of reperfusion. Four groups were constituted: control, pyruvate: (2 mm) added to cardioplegic and Ringer-lactate solutions, FeTPPS: (10 microm) perfused during the reperfusion, and a combination of both treatments. Lactate dehydrogenase (LDH) activity was assessed during the reperfusion to evaluate the level of cardiac injury. Oxidative stress was evaluated on heart slices using a fluorescent probe: dihydroethidium, and the collagen content was assessed using picro-Sirius coloration. Global post-ischemic recovery in the control group was about 35% of pre-ischemic values. Results showed that addition of pyruvate led to an increase in myocardial function and to a decrease in LDH activity released during the reperfusion. FeTPPS protected against injury after cardioplegic arrest during reperfusion. No additive effect of the two treatments (pyruvate + FeTPPS) was observed. The collagen content was better preserved in the FeTPPS group than in the control and pyruvate groups. In conclusion, this study shows that peroxynitrite plays an important role in the functional and cellular alterations associated with cardiac ischemia-reperfusion sequences and confirms that pyruvate helped to preserve myocardial function. The use of the peroxynitrite decomposition catalyst (FeTPPS) may help to improve myocardial preservation during a prolonged ischemia sequence.Fundamental and Clinical Pharmacology 04/2007; 21(2):173-80. · 1.99 Impact Factor