The effects of the modulation of NMDA receptors by homocysteine thiolactone and dizocilpine on cardiodynamics and oxidative stress in isolated rat heart

Considering the adverse effects of DL-homocysteine thiolactone hydrochloride (DL-Hcy TLHC) on vascular function and the possible role of oxidative stress in these mechanisms, the aim of this study was to assess the influence of DL-Hcy TLHC alone and in combination with specific inhibitors of important gasotransmitters, such as L-NAME, DL-PAG, and PPR IX, on cardiac contractility, coronary flow, and oxidative stress markers in an isolated rat heart. The hearts were retrogradely perfused according to the Langendorff technique at a 70 cm H2O and administered 10 μM DL-Hcy TLHC alone or in combination with 30 μM L-NAME, 10 μM DL-PAG, or 10 μM PPR IX. The following parameters were measured:dp/dtmax,dp/dtmin, SLVP, DLVP, MBP, HR, and CF. Oxidative stress markers were measured spectrophotometrically in coronary effluent through TBARS, NO2,O2-, and H2O2concentrations. The administration of DL-Hcy TLHC alone decreaseddp/dtmax, SLVP, and CF but did not change any oxidative stress parameters. DL-Hcy TLHC with L-NAME decreased CF,O2-, H2O2, and TBARS. The administration of DL-Hcy TLHC with DL-PAG significantly increaseddp/dtmax but decreased DLVP, CF, and TBARS. Administration of DL-Hcy TLHC with PPR IX caused a decrease indp/dtmax, SLVP, HR, CF, and TBARS.

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Hypoxia/Reoxygenation of isolated rat heart mitochondria causes cytochrome c release and oxidative stress; evidence for involvement of mitochondrial nitric oxide synthase

Journal of Molecular and Cellular Cardiology ◽

10.1016/j.yjmcc.2007.05.019 ◽

2007 ◽

Vol 43 (4) ◽

pp. 411-419 ◽

Cited By ~ 35

Author(s):

Woineshet J. Zenebe ◽

Rafal R. Nazarewicz ◽

Mordhwaj S. Parihar ◽

Pedram Ghafourifar

Keyword(s):

Oxidative Stress ◽

Nitric Oxide ◽

Rat Heart ◽

Isolated Rat Heart ◽

Cytochrome C Release ◽

Mitochondrial Nitric Oxide Synthase ◽

Rat Heart Mitochondria ◽

Oxide Synthase ◽

And Oxidative Stress ◽

Isolated Rat

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Protection of isolated rat heart from oxidative stress by exogenous creatine phosphate

Journal of Molecular and Cellular Cardiology ◽

10.1016/0022-2828(89)91494-6 ◽

1989 ◽

Vol 21 (1) ◽

pp. 67-73 ◽

Cited By ~ 25

Author(s):

R Zucchi

Keyword(s):

Oxidative Stress ◽

Rat Heart ◽

Creatine Phosphate ◽

Isolated Rat Heart ◽

Isolated Rat

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P561Acute effects of dronedarone and amiodarone on functional, morphological and oxidative stress parameters in isolated rat heart with hypertension

EP Europace ◽

10.1093/europace/euaa162.379 ◽

2020 ◽

Vol 22 (Supplement_1) ◽

Author(s):

S Simovic ◽

J Jeremic ◽

G Davidovic ◽

I Srejovic ◽

S Mitrovic ◽

...

Keyword(s):

Oxidative Stress ◽

Rat Heart ◽

Structural Changes ◽

Perfusion Pressure ◽

Coronary Perfusion Pressure ◽

Isolated Rat Heart ◽

Coronary Perfusion ◽

Acute Administration ◽

Isolated Hearts ◽

Isolated Rat

Abstract Introduction Amiodarone represents the most widely used antiarrhythmic drug, even though it has been shown that it has negative inotropic and lusitropic effect in healthy hears. On the other hand, dronedarone reduces the risk of recurrent atrial fibrillation, but with increased early mortality related to the worsening of heart failure. However, the mechanisms responsible for these fatal outcomes remain unclear and require further examinations. Purpose To investigate acute, direct effects of Dronedarone and Amiodarone on cardiac contractility, coronary flow and oxidative stress parameters in isolated rat heart with hypertension. Methods The present study was carried out on 18 isolated hearts of spontaneously hypertensive Wistar Kyoto male rats (6 weeks old, bodyweight 200 ± 10 g). After isolation, all hearts were retrogradely perfused according to Langendorff technique with a gradually increment of coronary perfusion pressure (CPP from 40 to 120 cm H2O) and randomly divided into 3 groups: Control (n = 6), Amiodarone (n = 6, isolated hearts perfused with Amiodarone in dose of 3 umol), Dronedarone (n = 6, isolated hearts perfused with Dronedarone in dose of 1.8 umol). During ex vivo protocol continuously were registered cardiac contractility parameters and coronary flow, while from collected coronary venous effluent markers of oxidative stress were measured. All hearts were then fixated and stained with Hematoxylin/eosin. Results Dronedarone severely depressed the function of all cardiodynamic parameters of the heart compared with Amiodarone or Control while Amiodarone intensified the function of the isolated rat heart with hypertension compared to Control (dp/dt max mmHg/s at coronary perfusion pressure 120cmH2O Dronedarone vs. Amiodarone vs. Control 579.733 ± 202.27 vs. 3063.65 ± 467.93 vs. 2682.88 ± 368.75; p < 0.001. dp/dt min mmHg/s 120cmH2O -352.13 ± 204.65 vs. 1960 ± 242.21 vs. -1858.83 ± 118.23; p < 0.001. SLVP mmHg at CPP 120cmH20 27.8 ± 3.46 vs. 98.95 ± 11.78 vs. 71.45 ± 7.56; p < 0.001. DLVP mmHg at CPP 120cmH2O 6.32 ± 0.49 vs. 4.83 ± 0.54 vs. 0.85 ± 0.35; p < 0.001). Acute administration of Dronedarone decreased the level of NO2- and increased the level of H2O2 , while Amiodarone heightens O2- levels (O2- nmol/min g wt at coronary perfusion pressure 120cmH2O Dronedarone vs. Amiodarone vs. Control 28.62 ± 2.54 vs. 77.3 ± 8.86 vs. 31.72 ± 4.56; p < 0.001. H2O2 nmol/min g wt at CPP 120cmH2O 92.56 ± 11.65 vs. 48.63 ± 10.11 vs. 42.84 ± 84; p < 0.001. NO2- nmol/min g wt at CPP 120cmH2O 38.61 ± 4.94 vs. 82.28 ± 5.76 vs. 64.71 ± 3.51; p < 0.001). Pathohistological, structural changes were observed in both, experimental groups. Conclusions Acute administration of Dronedarone depresses cardiac function in isolated, working rat heart with hypertension, with decreasing the NO2- levels, increasing the level of H2O2 and enhanced structural changes when compared to Amiodarone.

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