Anica Petkovic

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

Objective 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.

Impact of hyperbaric oxygenation on oxidative stress in diabetic patients

Taking into consideration that a high concentration of oxygen can express toxic effects due to production of reactive oxygen species (ROS), the aim of our investigation was to establish the influence of hyperbaric oxygenation on oxidative stress parameters and antioxidant enzymes in patients with diabetes mellitus (DM) type 2. Investigation included 50 patients with DM type 2 divided into two groups. The first group consisted of 25 patients, mean age 70 years, mean duration of illness 12 years and without manifest peripheral vascular complications (Wagner 0). The second group consisted of 25 patients, mean age 74 years, mean duration of illness 17 years and with manifest peripheral vascular complications (Wagner 1-5). All patients underwent the same therapeutic protocol, which included 10 hyperbaric oxygenation therapies, once a day for a duration of 60 minutes, with an average partial oxygen pressure of 1.7 atmospheres absolute (ATA). In blood samples the following parameters of redox balance were determined: levels of nitrites (NO₂-), index of lipid peroxidation (TBARS), superoxide anion radical (O₂-), hydrogen peroxide (H₂O₂) and antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT). Our results clearly show that hyperbaric oxygen (HBO₂) therapy does not have a pro-oxidative effect. Additionally, it seems that this procedure strongly mobilized the antioxidant enzyme system, thus improving defense from oxidative damage. All significant data are marked as P ⟨0.05. Our results have shown that in terms of ROS production, HBO₂ can be safe to use in patients suffering from DM type 2 with or without vascular complications.

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

Abstract 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.

Effects of Ischemic and Proton Pump Inhibitors Preconditioning on Oxidative Stress of Isolated Rat Heart

Abstract 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

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

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 cmH2O. 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.

THE EFFECTS OF DICLOFENAC AND IBUPROFEN ON HEART FUNCTION AND OXIDATIVE STRESS MARKERS IN THE ISOLATED RAT HEART

ABSTRACT Eicosanoids lead to the promotion of inflammation, cause fever and pain and have many other eff ects. NSAIDs block the action of cyclooxygenase (COX) during the process of converting arachidonic acid into inflammatory mediators, thus reducing the symptoms of inflammation. Investigations focusing on nonselective COX inhibitors, used in high doses, revealed harmful eff ects on myocardial function. Th e aim of our study was to assess the eff ects of two nonselective NSAIDs, diclofenac and ibuprofen, on cardiodynamic parameters, coronary flow and oxidative stress biomarkers in isolated rat hearts. Th e hearts of male Wistar albino rats were excised and retrogradely perfused according to the Langendorff technique at gradually increased coronary perfusion pressures (40-120 cm H2O). Th e experiments were performed under controlled conditions (Krebs-Henseleit physiological solution). Th e hearts were perfused with 10 μmol/l diclofenac and 10 μmol/l ibuprofen. Th e heart function parameters, including the maximum rate of pressure development (dp/dt max), minimum rate of pressure development (dp/dt min), systolic left ventricular pressure (SLVP), diastolic left ventricular pressure (DLVP), mean perfusion pressure (MBP) and heart rate (HR), were continuously registered. Coronary flow (CF) was measured flowmetrically. Oxidative stress markers, including the index of lipid peroxidation measured as TBARS, nitric oxide measured through nitrites (NO2 -), superoxide anion radical (O2 -), and hydrogen peroxide (H2O2) in the coronary venous effluent, were assessed spectrophotometrically. Our results showed that diclofenac aff ected cardiodynamic parameters more significantly than did ibuprofen. Furthermore, the present data indicate that both estimated COX inhibitors do not promote the production of reactive oxygen species. SAŽETAK 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.