The effect the superoxide dismutase in the myocardium during reperfusion in the dog

Kónya, L; Kékesi, Violetta; Juhász-Nagy, S; Fehér, János

doi:10.1016/0891-5849(92)90147-9

Cited by 17 publications

(11 citation statements)

References 20 publications

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“…Among the candidate radical scavengers tested to date, early efforts focused primarily on superoxide dismutase mimetics and catalase. These approaches reduced infarct size in some 26–29 (but not all 30 ) animal studies and also decreased microvascular damage and reduced no-reflow. 30 Despite promising results in animal studies, these strategies do not appear to translate to beneficial effects in clinical trials.…”

Section: Discussionmentioning

confidence: 99%

Reduction of Ischemia/Reperfusion Injury With Bendavia, a Mitochondria‐Targeting Cytoprotective Peptide

Kloner

Hale

Dai

et al. 2012

JAHA

130

122

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BackgroundManifestations of reperfusion injury include myocyte death leading to infarction, contractile dysfunction, and vascular injury characterized by the “no-reflow” phenomenon. Mitochondria-produced reactive oxygen species are believed to be centrally involved in each of these aspects of reperfusion injury, although currently no therapies reduce reperfusion injury by targeting mitochondria specifically.Methods and ResultsWe investigated the cardioprotective effects of a mitochondria-targeted peptide, Bendavia (Stealth Peptides), across a spectrum of experimental cardiac ischemia/reperfusion models. Postischemic administration of Bendavia reduced infarct size in an in vivo sheep model by 15% (P=0.02) and in an ex vivo guinea pig model by 38% to 42% (P<0.05). In an in vivo rabbit model, the extent of coronary no-reflow was assessed with Thioflavin S staining and was significantly smaller in the Bendavia group for any given ischemic risk area than in the control group (P=0.0085). Myocardial uptake of Bendavia was ≈25% per minute, and uptake remained consistent throughout reperfusion. Postischemic recovery of cardiac hemodynamics was not influenced by Bendavia in any of the models studied. Isolated myocytes exposed to hypoxia/reoxygenation showed improved survival when treated with Bendavia. This protection appeared to be mediated by lowered reactive oxygen species–mediated cell death during reoxygenation, associated with sustainment of mitochondrial membrane potential in Bendavia-treated myocytes.ConclusionsPostischemic administration of Bendavia protected against reperfusion injury in several distinct models of injury. These data suggest that Bendavia is a mitochondria-targeted therapy that reduces reperfusion injury by maintaining mitochondrial energetics and suppressing cellular reactive oxygen species levels. (J Am Heart Assoc. 2012;1:e001644 doi: 10.1161/JAHA.112.001644.)

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Section: Discussionmentioning

confidence: 99%

Reduction of Ischemia/Reperfusion Injury With Bendavia, a Mitochondria‐Targeting Cytoprotective Peptide

Kloner

Hale

Dai

et al. 2012

JAHA

130

122

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“…Significant evidence suggests that increased ROS scavenging ability decreases reperfusion injury. Up-regulation of mitochondrial antioxidant capacity, either by direct infusion of ROS scavengers [16] or increased protein expression [17, 18] results in cardioprotection.…”

Section: Discussionmentioning

confidence: 99%

Cardiac arrhythmias induced by glutathione oxidation can be inhibited by preventing mitochondrial depolarization

Brown¹,

Aon²,

Frasier³

et al. 2010

Journal of Molecular and Cellular Cardiology

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We have previously proposed that the heterogeneous collapse of mitochondrial inner membrane potential (ΔΨ m ) during ischemia and reperfusion contributes to arrhythmogenesis through the formation of metabolic sinks in the myocardium, wherein clusters of myocytes with uncoupled mitochondria and high K ATP current levels alter electrical propagation to promote reentry. Single myocyte studies have also shown that cell-wide ΔΨ m depolarization, through a reactive oxygen species (ROS) -induced ROS release mechanism, can be triggered by global depletion of the antioxidant pool with diamide, a glutathione oxidant. Here we examine whether diamide causes mitochondrial depolarization and promotes arrhythmias in normoxic isolated perfused guinea pig hearts. We also investigate whether stabilization of ΔΨ m with a ligand of the mitochondrial benzodiazepine receptor (4′-chlorodiazepam; 4-ClDzp) prevents the formation of metabolic sinks and, consequently, precludes arrhythmias. Oxidation of the GSH pool was initiated by treatment with 200μM diamide for 35 minutes, followed by washout. This treatment increased GSSG and decreased both total GSH and the GSH/GSSG ratio. All hearts receiving diamide transitioned from sinus rhythm into ventricular tachycardia and/or ventricular fibrillation during the diamide exposure: arrhythmia scores were 5.5 ± 0.5; n=6 hearts. These arrhythmias and impaired LV function were significantly inhibited by co-administration of 4-ClDzp (64μM): arrhythmia scores with diamide + 4-ClDzp were 0.4± 0.2 (n=5; P < 0.05 vs. diamide alone). Imaging ΔΨ m in intact hearts revealed the heterogeneous collapse of ΔΨ m beginning 20 minutes into diamide, paralleling the timeframe for the onset of arrhythmias. Loss of ΔΨ m was prevented by 4-ClDzp treatment, as was the increase in myocardial GSSG. These findings show that oxidative stress induced by oxidation of GSH with diamide can cause electromechanical dysfunction under normoxic conditions. Analogous to ischemia-reperfusion injury, the dysfunction depends on the mitochondrial energy state. Targeting the mitochondrial benzodiazepine receptor can prevent electrical and mechanical dysfunction in both models of oxidative stress.

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“…SarcKATP channels opening reduces the action potential duration and effective refractory period (Aidonidis et al, 2009;Ferrier & Howlett, 2005) which in turn increases the incidence of cardiac arrhythmia (Billman, 2008;Billman et al, 2004). There is credible evidence that during reperfusion, production of oxygen free radicals increase in ischemic tissue (Bolli et al, 1989;Manning et al, 1988) and the use of ROS (reactive oxygen species) scavengers is associated with successful decrease in the reperfusion-induced arrhythmias (Cho et al, 2007;Hicks et al, 2007;Konya et al, 1992). Existing documents show the antioxidant properties of saffron (Asdaq & Inamdar, 2010;Hosseinzadeh et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Protective effects of saffron (Crocus sativus) against lethal ventricular arrhythmias induced by heart reperfusion in rat: A potential anti-arrhythmic agent

Joukar

Ghasemipour-Afshar

Sheibani

et al. 2013

Pharmaceutical Biology

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Context: Saffron (Crocus sativus L.) has been used as a cuisine spice in eastern and western societies for thousands of years. In traditional medicine, saffron is recommended for the treatment of various kinds of disorders including heart palpitations. Objective: We investigated the hypothesis of the protective effect of saffron on lethal cardiac arrhythmias induced by heart ischemia-reperfusion in rat. Materials and methods: Animals were divided into a control (CTL) group that received tap water, Saf50, Saf100 and Saf200 groups that were orally treated with aqueous extracts of saffron, at dosages of 50, 100 and 200 mg/kg/day, respectively, and amiodarone (Amio) group that orally received 30 mg/kg/day for seven days. On day 8, heart ischemia-reperfusion was induced by ligation and releasing of the left anterior descending coronary artery. Results: During reperfusion, the numbers and durations of ventricular fibrillation (VF) decreased in all groups compared to the CTL group (p50.05). Ventricular tachycardia (VT)/VF numbers (3.2 AE 1.2), durations (4.9 AE 2.6) and also arrhythmia severity (1.9 AE 0.35) were decreased significantly in the Saf100 group versus CTL group values (18.4 AE 11.6, 52 AE 31 and 3.3 AE 0.3, respectively). The PR and QTcn intervals of ECG were significantly longer in the Saf200 group (p50.001 versus CTL). The other doses of saffron only significantly prolonged the QTcn interval. Conclusion:The results suggest that pretreatment with saffron, especially at the dosage of 100 mg/kg/day, attenuates the susceptibility and incidence of fatal ventricular arrhythmia during the reperfusion period in the rat. This protective effect is apparently mediated through reduction of electrical conductivity and prolonging the action potential duration.

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The effect the superoxide dismutase in the myocardium during reperfusion in the dog

Cited by 17 publications

References 20 publications

Reduction of Ischemia/Reperfusion Injury With Bendavia, a Mitochondria‐Targeting Cytoprotective Peptide

Reduction of Ischemia/Reperfusion Injury With Bendavia, a Mitochondria‐Targeting Cytoprotective Peptide

Cardiac arrhythmias induced by glutathione oxidation can be inhibited by preventing mitochondrial depolarization

Protective effects of saffron (Crocus sativus) against lethal ventricular arrhythmias induced by heart reperfusion in rat: A potential anti-arrhythmic agent

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