Effects of ischemia and omeprazole preconditioning on functional recovery of isolated rat heart

AbstractObjective:The aim of this study was to compare protective effects of ischemic and potential protective effects of pharmacological preconditioning with omeprazole on isolated rat heart subjected to ischemia/reperfusion.Methods:The hearts of male Wistar albino rats were excised and perfused on a Langendorff apparatus. In control group (CG) after stabilization period, hearts were subjected to global ischemia (perfusion was totally stopped) for 20 minutes and 30 minutes of reperfusion. Hearts of group II (IPC) were submitted to ischemic preconditioning lasting 5 minutes before 20 minutes of ischemia and 30 minutes of reperfusion. In third group (OPC) hearts first underwent preconditioning lasting 5 minutes with 100μM omeprazole, and then submitted 20 minutes of ischemia and 30 minutes of reperfusion.Results:Administration of omeprazole before ischemia induction had protective effect on myocardium function recovery especially regarding to values of systolic left ventricular pressure and dp/dt max. Also our findings are that values of coronary flow did not change between OPC and IPC groups in last point of reperfusion.Conclusion:Based on our results it seems that ischemic preconditioning could be used as first window of protection after ischemic injury especially because all investigated parameters showed continuous trend of recovery of myocardial function. On the other hand, preconditioning with omeprazole induced sudden trend of recovery with positive myocardium protection, although less effective than results obtained with ischemic preconditioning not withstand, we must consider that omeprazole may be used in many clinical circumstances where direct coronary clamping for ischemic preconditioning is not possible

Assessment of hemostatic disturbances in women with established rheumatoid arthritis

© 2019, The Author(s). Objectives: This study was aimed to assess hemostatic disturbances in female patients with established rheumatoid arthritis (RA) in relation to menopausal status and disease activity. Method: Ninety women were included in the study, 42 patients and 48 age-matched healthy controls. There were no differences between the investigated groups regarding the presence of traditional cardiovascular risk factors. Two global hemostatic assays were employed, namely endogenous thrombin potential (ETP) and overall hemostasis potential (OHP). The parameters of the ETP assay (ETP, C-max, t-lag, t-max) and OHP assay (overall coagulation potential (OCP) and overall fibrinolytic potential (OFP)) were assessed. Moreover, the parameters of the fibrin clot (lag time, Max Abs, and slope) were measured by clot turbidity and scanning electron microscopy (SEM). Both patients and controls were divided into four subgroups according to menopause status. Results: The premenopausal controls differed significantly from all other subgroups in terms of diminished levels of ETP (p = 0.02), C-max (p = 0.01), OCP (p = 0.02), OHP (p = 0.001), and Max Abs (p = 0.008), while OFP (p = 0.0001) was increased. This tendency was not seen in the premenopausal RA patients compared with the postmenopausal RA patients. SEM images showed denser clots composed of thinner fibers in samples from RA patients. The disease activity measured by DAS28 correlated with OCP and OHP (r = 0.54; p = 0.001 and r = 0.44; p = 0.003, respectively) indicating persistent hypercoagulable condition in the whole group of RA patients. Conclusions: Our results point towards coagulation activation in premenopausal women with established RA. The patients were well characterized, which enabled assessment in a real-life setting.Key Points• Extensive assessment points towards persistent coagulation activation in premenopausal women with established rheumatoid arthritis.• Impaired thrombin generation and fibrin formation are associated with menopause in healthy women, while rheumatoid arthritis closes the gap within patients regarding menopause.• Fibrin morphology is unfavorably altered and fibrinolysis is decreased in patients with established rheumatoid arthritis.• Increased activity of thrombin activatable fibrinolysis inhibitor (TAFI) may contribute to impaired fibrinolysis in patients with rheumatoid arthritis

Effects of ischemic and proton pump inhibitors preconditioning on oxidative stress of isolated rat heart

© 2018, University of Kragujevac, Faculty of Science. All rights reserved. Aim of present study was to determine the participation of various biomarkers of oxidative damage: nitrite (NO2 -), superoxide anion radicals (O2 -), index of lipid peroxidation (TBARS) and hydrogen peroxide (H2O2) in coronary circulation after application of the different models of preconditioning such as ischemic and preconditioning with proton pump inhibitors. Examining a biochemical markers of oxidative damage we did not notice any increased production values of any parameter, according to that we can hypothesize that possible occurrence of reperfusion injury after ischemia and PPIs preconditioning is not mediated by this mechanism. Due to the very difficult and controversial application of ischemic preconditioning in clinical practice, the results of this study suggest that in the future proton pump inhibitors can contribute to the prevention of myocardial damage following ischemia

Is 3 Weeks of Exercise Enough to Change Blood Pressure and Cardiac Redox State in Hypertensive Rats?

The investigation was aimed to evaluate the effects of 3-weeks swimming exercise on blood pressure and redox status in high-salt-induced hypertensive rats. Male Wistar albino rats (n=40, 6 weeks old) were divided into 4 groups: 1. hypertensive rats that swam for 3 weeks; 2. sedentary hypertensive control rats; 3. normotensive rats that swam for 3 weeks; 4. sedentary normotensive control rats. Hypertensive animals were on high concentrated sodium (8% NaCl) solution for 4 weeks (period of induction of hypertension). After sacrificing, hearts were isolated and perfused according to Langendorff technique at gradually increased coronary per-fusion pressure from 40–120 cmH2O. The oxidative stress markers were determined in coronary venous effluent: the index of lipid peroxidation (measured as TBARS), nitrites (NO2−), superoxide anion radical (O2−) and hydrogen peroxide (H2O2). Swimming did not lead to significant changes in levels of TBARS, NO2−, O2− in any of compared groups while levels of H2O2 were significantly higher in swimming hyper-tensive group comparing to swimming normotensive group at coronary perfusion pressure of 80–120 cmH2O. Our results indicate that the short-term swimming start to reduce blood pressure. In addition it seems that this type of swimming duration does not promote cardiac oxidative stress damages

The Effects of Diclofenac and Ibuprofen on Heart Function and Oxidative Stress Markers in the Isolated Rat Heart

Eikosanoidi dovode do zapaljenja, uzrokuju groznicu i bol, i imaju mnoge druge efekte na organizam. NSAID onemogućavaju delovanje ciklooksigenaze (COX) u procesu konvertovanja arahidonske kiseline u medijatore zapaljenja, i na taj način smanjuju simptome zapaljenja. Istraživanja koja se bave primenom neselektivnih inhibitora COX, koji se koriste u visokim dozama, pokazala su njihove štetne efekte na funkciju miokarda. Cilj našeg istraživanja je bio da ispita efekte neselektivnih NSAID, diklofenaka i ibuprofena, na kardiodinamske parametre, koronarni protok i biomarkere oksidativnog stresa izolovanog srca pacova. Srca mužijaka Wistar albino pacova su uzimana i retrogradno perfundovana prema Langedorff -ovoj tehnici sa postepenim povećanjem perfuzionog pritiska (40-120 cm H2O). Eksperimenti su prvo izvođeni u kontrolnim uslovima (primena fiziološkog Krebs-Henseleit-ovog rastvora), nakon čega su srca perfundovana sa: 10 μmol/l dikolfenaka i 10 μmol/l ibuprofena. Parametri srčane funkcije koji su kontinuirano praćeni su: maksimalna stopa razvoja pritiska (dp/dt max), minimalna stopa razvoja pritiska (dp/dt min), sistolni pritisak u levoj komori (SLVP), dijastolni pritisak u levoj komori (DLVP), srednji perfuzioni pritisak (MBP) i frekvenca srčanog rada (HR). Koronarni protok (CF) je registrovan floumetrijski. Markeri oksidativnog stresa: indeks lipidne peroksidacije meren kao TBARS, azot-monoksid utvrđivan preko nitrata (NO2 -), superoksid anjon radikal (O2 -), i vodonik peroksid (H2O2) su mereni spektrofotometrijski u koronarnom venskom efluentu. Naši rezultati su pokazali da diklofenak ispoljava značajniji uticaj na kardiodinamske parametre u odnosu na ibuprofen. Pored toga, rezultati ove studije su pokazali da oba ispitivana inhibitora COX ne dovode po produkcije reaktivnih vrsta kiseonika

The effects of sulfur-containing compounds on redox status in homocysteine-treated rats

© 2019 Polish Pharmaceutical Society. All Rights Reserved. There is growing interest in the activity of sulfur-containing compounds on redox balance in physiological and pathological conditions, considering that some of these compounds have not only antioxidative but also pro-oxidative activities. The aim of this study was to assess possible differences in the effects of various sulfur-containing compounds on redox balance of cardiovascular system in its physiological state and in the early onset of hyperhomocysteinemia. This experimental study divided Wistar albino rats into two groups: Saline-treated (control) and DL-homocysteine-treated (experimental group). Rats from experimental group were subjected to subchronic subcutaneous administration of DL-homocysteine at dose of 0.45 Imol/g body weight twice a day for 2 weeks. At the end of this period, rats were sacrificed, and blood samples were collected to be analyzed for homocysteine concentration and systemic oxidative stress. Isolated rat hearts were excised and attached to the Langendorff apparatus. To assess the effects of acute administration of L-methionine, L-cysteine, N-acetylcysteine, and sodium hydrogen sulfide, the hearts were perfused individually with each of the mentioned substances at the same single dose of 0.5 mmol/L for 5 min. In collected samples of coronary venous effluent oxidative stress biomarkers were determined using spectrophotometry. Total homocysteine level was significantly higher in the experimental group than in the control group, and the effects of applied sulfur-containing compounds were significantly different in experimental and control groups. DL-homocysteine induced considerable changes in the functioning of a cardiovascular system even before an increase in plasma homocysteine values, and action of sulfur-containing compounds varied depending on the presence of homocysteine

Comparison of training and detraining on redox state of rats: Gender specific differences

© 2018 Slovak Academy of Sciences. All rights reserved. Given the fact that oxidative stress response induced by training/detraining has still not been clarified and may be influenced by gender, the aim of our investigation was to compare the effects of swimming training and detraining on oxidative and antioxidative parameters in rats, with a special focus on sex differences. Wistar albino rats (n = 64) were divided into 4 groups: control, trained group, groups exposed to 2 and 4 weeks of detraining. Each group included two subgroups: males and females. After sacrificing, hearts were isolated and retrogradely perfused according to Langendorff technique. Levels of superoxide anion radical, hydrogen peroxide, nitrites and thiobarbituric acid reactive substances were measured in plasma and coronary venous effluent, while reduced glutathione, activities of superoxide dismutase and catalase were measured in erythrocytes. Our results indicate that swimming training doesn't promote oxidative damage, nor act protectively within the heart. However, 2 and 4 weeks of detraining led to a partial lost in exercise-induced adaptation. It seems that moderate-intensity physical exercise of sufficient duration leads to beneficial adaptations, which may be partially lost during detraining period. Positive antioxidative effects of training remained longer in males. Findings of present study may help in elucidation of training and detraining effects on modulation of redox homeostasis, especially from aspect of gender differences

The Effects of Potassium Cyanide on the Functional Recovery of Isolated Rat Hearts after Ischemia and Reperfusion: The Role of Oxidative Stress

© 2018 Anica M. Petkovic et al. This investigation is aimed at examining the effects of pharmacological PostC with potassium cyanide (KCN) on functional recovery, gene expression, cytochrome c expression, and redox status of isolated rat hearts. Rats were divided into the control and KCN groups. The hearts of male Wistar albino rats were retrogradely perfused according to the Langendorff technique at a constant perfusion pressure of 70 cmH 2 O. After stabilisation, control hearts were subjected to global ischemia (5 minutes), followed by reperfusion (5 minutes), while experimental hearts underwent global ischemia (5 minutes) followed by 5 minutes of reperfusion with 10 μmol/L KCN. The following parameters of heart function were measured: maximum and minimum rates of pressure development, systolic and diastolic left ventricular pressure, heart rate, and coronary flow. Levels of superoxide anion radical, hydrogen peroxide, nitrites, and index of lipid peroxidation (measured as thiobarbituric acid-reactive substances) were measured in coronary venous effluent, and activity of catalase was determined in heart tissue. Expression of Bax, Bcl-2, SOD-1, SOD-2, and cytochrome c was studied as well. It was shown that expression of Bax, Bcl-2, and SOD-2 genes did not significantly differ between groups, while expression of SOD-1 gene and cytochrome c was lower in the KCN group. Our results demonstrated that KCN improved the recovery of myocardial contractility and systolic and diastolic function, enhanced catalase activity, and diminished generation of prooxidants. However, all possible mechanisms and potential adverse effects of KCN should be further examined in the future

Training/detraining-induced gender specific functional adaptations of isolated rat heart

Background/Aim. Mechanisms responsible for the bene-ficial effects of aerobic exercise training on cardiovascular function are well known, but detraining effects on myo-cardial parameters have not been adequately elucidated. Therefore, the study aimed to determine the occurrence and speed of cardiac adaptation reversibility after the ces-sation of aerobic exercise and to reveal gender differences in achieved effects of training/detraining. Methods. Fe-male and male Wistar albino rats were divided into the fol-lowing groups: Control, trained, and two detrained groups. Hearts were perfused according to the Langendorff tech-nique and the following cardiodynamic parameters were determined: The maximum and minimum rate of pressure development in the left ventricle (dp/dt max and dp/dt min, respectively), systolic and diastolic left ventricular pressure (SLVP and DLVP, respectively), heart rate (HR), and coronary flow. Results. Training significantly reduced values of dp/dt max, dp/dt min, and SLVP in males and females, and coronary flow in males. Detraining caused a reversion of those changes, which was gender-specific. In females, levels of SLVP were higher after 4 weeks of de-training compred to training, and after 2 weeks of detrain-ing. Values of SLVP were lower in both detraining periods compared to training in males. Males had higher coronary flow after 2 weeks of detraining. Simultaneously, coronary flow was reduced in the 4th week of detraining in females. Conclusion. By using a model of the isolated rat heart, the present study confirmed the existence of training-induced changes in cardiac function. Cessation of training was followed by the loss of those adaptations, faster in males than females

Protective effects of Galium verum L. extract against cardiac ischemia/reperfusion injury in spontaneously hypertensive rats

Copyright © 2019 Jovana Bradic et al. Galium verum L. (G. verum, lady’s bedstraw) is a perennial herbaceous plant, belonging to the Rubiaceae family. It has been widely used throughout history due to multiple therapeutic properties. However, the effects of this plant species on functional recovery of the heart after ischemia have still not been fully clarified. Therefore, the aim of our study was to examine the effects of methanol extract of G. verum on myocardial ischemia/reperfusion (I/R) injury in spontaneously hypertensive rats (SHR), with a special emphasis on the role of oxidative stress. Rats involved in the research were divided randomly into two groups: control (spontaneously hypertensive rats (SHR)) and G. verum group, including SHR rats treated with the G. verum extract (500 mg/kg body weight per os) for 4 weeks. At the end of the treatment, in vivo cardiac function was assessed by echocardiography. Rats were sacrificed and blood samples were taken for spectrophotometric determination of systemic redox state. Hearts from all rats were isolated and retrogradely perfused according to the Langendorff technique. After a stabilization period, hearts were subjected to 20-minute ischemia, followed by 30-minute reperfusion. Levels of prooxidants were spectrophotometrically measured in coronary venous effluent, while antioxidant enzymes activity was assessed in heart tissue. Cell morphology was evaluated by hematoxylin and eosin (HE) staining. 4-week treatment with G. verum extract alleviated left ventricular hypertrophy and considerably improved in vivo cardiac function. Furthermore, G. verum extract preserved cardiac contractility, systolic function, and coronary vasodilatory response after ischemia. Moreover, it alleviated I/R-induced structural damage of the heart. Additionally, G. verum extract led to a drop in the generation of most of the measured prooxidants, thus mitigating cardiac oxidative damage. Promising potential of G. verum in the present study may be a basis for further researches which would fully clarify the mechanisms through which this plant species triggers cardioprotection