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The aim of this study was to examine and compare the influence of preconditioning, perconditioning, and postconditioning with creatine phosphate (PCr) on functional recovery and production of prooxidants in isolated rat hearts subjected to ex vivo ischemic–reperfusion (I–R) injury on a Langendorff apparatus. Wistar albino rats (male, n = 40) were divided into four groups: control and groups in which PCr (0.5 mmol/L, 5 min) was perfused before (Pre group), after (Post group), or during (Per group) ex vivo induced ischemia. PCr application was associated with the great benefits of preserving cardiac contractility (in Pre group 100.96% for +(d P/d t max) and 97.61% for −(d P/d t max), in Per group 96.72% for +(d P/d t max) and 95.60% for −(d P/d t max), and in Post group 143.84% for +(d P/d t max) and 104.36% for −(d P/d t max) in relation to the stabilization). In addition, PCr application prevented the increase in prooxidative markers during I–R injury in all therapeutic modalities. The most intensive benefits in the current investigation were observed when PCr was applied during the period of ischemia because the lowest fluctuations in the parameters of cardiac function and oxidative stress were observed. Overall, the results of this study highlight PCr-induced cardioprotection with promising prospects for future clinical use.

This study evaluated the effect of sacubtril/valsartan on cardiac remodeling, molecular and cellular adaptations in experimental (rat) model of hypertension-induced hypertrophic cardiomyopathy. Thirty Wistar Kyoto rats; 10 normal (control) and 20 rats with confirmed hypertension-induced hypertrophic cardiomyopathy (HpCM) were used for this study. The HpCM group was further subdivided into untreated, and sacubitril/valsartan treated group. Myocardial structure and function were assessed using echocardiography, Langendorff’s isolated heart experiment, blood sampling and qualitative polymerase chain reaction. Left ventricular internal diameter in systole (0.5 vs 0.22 cm, P

The aim of our study was to investigate the influence of 12 weeks of consumption of chokeberry extract on redox status, body composition, lipid profile, and biochemical parameters in active handball players. The study included 16 handball players aged 16–24 years (20.26 ± 2.86 years). Every morning before training, players received 30 mL of liquid chokeberry extract for 12 weeks during the regular competition season. The research consisted of morphofunctional and biochemical testing, which was performed at three points (at the beginning of the study and at 6 and 12 weeks after extract consumption). After the chokeberry extract treatment, we observed significant changes in three main aspects. The 12 week supplementation with chokeberry extract decreased the levels of prooxidants (TBARS and nitrites) and increased catalase activity. Analyzing the dynamic of body composition showed a decrease in body fat (9.4 ± 0.5 vs. 7.3 ± 0.6 kg) as well as its percent in a body (11.4 ± 0.4% vs. 8.8 ± 0.4%). On the other hand, the analysis showed an increase of high-density lipoprotein (1.3 ± 0.3 vs. 1.6 ± 0.2 mmol/L) and hemoglobin (144.4 ± 11.7 vs. 151.7 ± 9.9 g/L) after 6 weeks of treatment. At the same time, a decrease in leukocytes (7.2 × 109 ± 2.8 vs. 6.5 ± 1.2 × 109/L) and an increase in red blood cells count (4.9 ± 0.4 × 109 vs. 5.5 ± 0.5 × 109/L) were observed. Overall, these results emphatically show that the use of chokeberry extract dietary supplement induced a wide range of beneficial effects in the examined group of athletes.

Background/Aim. Mechanisms responsible for the beneficial effects of aerobic exercise training on cardiovascular function are well known, but detraining effects on myocardial parameters have not been adequately elucidated. Therefore, the study aimed to determine the occurrence and speed of cardiac adaptation reversibility after the cessation 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 following groups: control, trained, and two detrained groups. Hearts were perfused according to the Langendorff technique 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 detraining compred to training, and after 2 weeks of detraining. 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.

The aim of our study was to assess and compare the effects of dipeptidyl peptidase 4 (DPP4) inhibitors, saxagliptin and sitagliptin, on metabolic control of disease and cardiac function in rats with diabetes mellitus type 2 (T2DM). This research would provide novel understanding into the potentially protective effects of DPP4 inhibitors in helping salvage of the heart exposed to ischaemia-reperfusion (I-R) injury. Forty-eight Wistar albino rats were randomly divided into four groups: CTRL, Control healthy group; T2DM, rats with T2DM; T2DM + Sit, rats with T2DM treated with 0.6 mg/kg of sitagliptin; T2DM + Sax, rats with T2DM treated with 0.45 mg/kg of saxagliptin for 3 weeks. At the end of the protocol, in vivo cardiac function was assessed by echocardiography, while in the blood samples glucose and insulin were determined. Additionally, ex vivo heart function was estimated on a model of I-R injury using Langendorff apparatus. Immunohistochemical analysis was used to determine the degree of myocardial apoptosis and necrosis, while DPP4 staining was performed to assess the cardiac DPP4 expression. Data were analyzed using a one-way analysis of variance (ANOVA) and the post hoc Bonferroni test for multiple comparisons. Improved glycoregulation was noticed in rats that received DPP4 inhibitors compared to untreated diabetic rats (P < .05). Moreover, better in vivo systolic function was observed in rats treated with both DPP4 inhibitors as evidenced by an increase in fractional shortening when compared to T2DM (P < .05). Most parameters of cardiac function in treated rats remained unaltered during reperfusion, thus suggesting that both drugs protected myocardium during flow restoration. Better effects on coronary circulation were achieved after sitagliptin application. Additionally, both DPP4 inhibitors showed similar potential to attenuate cardiac necrosis and apoptosis. Saxagliptin and sitagliptin might be efficient in preserving myocardial function and morphology in ex vivo induced I-R cardiac injury in rats with T2DM.

The aim of this study was to estimate the effects of natural low mineral water from the source "Sneznik-1/79" in Serbia on glycemia as well as heart function in rats with diabetes mellitus type 2 (T2DM), with the special emphasis on the role of the oxidative stress. Twenty Wistar albino rats (males, 4 weeks old at the beginning of the study, body weight 180 ± 20 g) were included in the study. Rats were divided randomly into 2 groups (10 animals per group): T2DM: rats with diabetes mellitus type 2 with free access to tap water; T2DM + SW: rats with diabetes mellitus type with free access to natural mineral water from "Sneznik-1/79". Glucose level, ex vivo cardiac function as well as systemic and cardiac redox state were assessed. At the end of the study protocol, glucose level was lower in diabetic rats who consumed mineral water. Moreover cardiac function wasn't affected by mineral water intake, however, significant antioxidant effects were observed. Our study suggests that 4-week consumption of low mineral water from the spring "Sneznik-1/79" has important role in regulation of glycemia and altering redox state in favor of elevated antioxidant capacity without affecting heart function. Based on our findings we may assume that low mineral water from the spring "Sneznik-1/79" has the potential to be used either as preventive strategy or as additional therapeutic strategy in management of T2DM.

Melissa officinalis L. (MO), traditionally referred to as lemon balm, is one of the lemon-scent aromatic herbs widely used in traditional medicine due to its calming, sedative, and anti-arrhythmic effects. Furthermore, several studies have linked its therapeutic potential with its antioxidant properties. Here, we aimed to evaluate and compare the content of active components, antioxidant, and anti-inflammatory potential of three different MO extracts (MOEs), ethanolic macerate (E1), aqueous (E2), and ethanolic (E3), obtained under reflux and their effects on systemic redox status after acute per os administration in vivo post-carrageenan application. The HPLC analysis revealed that the most abundant constituent in all the three extracts was rosmarinic acid (RA), with higher content in E1 and E3 than in E2 (P < 0.05). The highest flavonoid content was found in the aqueous extract, especially quercetin (P < 0.05). For the carrageenan-induced paw edema model, dark agouti rats were used and divided into the groups: Control, indomethacin, E1, E2, and E3 subgrouped according to applied doses: 50, 100, and 200 mg/kg. Ethanolic macerate (E1200) and aqueous (E2100) MOE were shown to be anti-inflammatory agents in the carrageenan paw edema model, with the most prominent edema inhibition in the sixth hour post-carrageenan (63.89% and 69.44%, respectively, vs. 76.67% in the indomethacin group). All the three extracts reduced the production of pro-oxidants H2O2 and TBARS post-carrageenan and increased GSH levels compared to control (P < 0.05). These data imply the possible future usage of MOEs to prevent inflammatory and oxidative stress-related diseases.

Taken into consideration that oxidative stress response after preconditioning with phosphodiesterase inhibitors (PDEIs) and moderate physical activity has still not been clarified, the aim of this study was to assess the effects of PDEIs alone or in combination with physical activity, on systemic redox status. The study was carried out on 96 maleWistar albinorats classified into two groups. The first group included animals exposed only to pharmacological preconditioning (PreC) maneuver (sedentary control (CTRL, 1 ml/day saline,n=12), nicardipine (6 mg/kg/day of NIC,n=12), vinpocetine (10 mg/kg/day of VIN,n=12), and nimodipine (NIM 10 mg/kg/day of,n=12). The second included animals exposed to preconditioning with moderate-intensity training (MIT) on treadmill for 8 weeks. After 5 weeks from the start of training, the animals were divided into four subgroups depending on the medication to be used for pharmacological PreC: moderate-intensity training (MIT+ 1 ml/day saline,n=12), nicardipine (MIT+ 6 mg/kg/day of NIC,n=12), vinpocetine (MIT+ 10 mg/kg/day of VIN,n=12), and nimodipine (MIT+ 10 mg/kg/day of NIM,n=12). After three weeks of pharmacological preconditioning, the animals were sacrificed. The following oxidative stress parameters were measured spectrophotometrically: nitrites (NO2−), superoxide anion radical (O2−), hydrogen peroxide (H2O2), index of lipid peroxidation (TBARS), superoxide dismutase (SOD), catalase (CAT), and reduced glutathione (GSH). Our results showed that PDE1 and MIT preconditioning decreased the release of prooxidants and improved the activity of antioxidant enzymes thus preventing systemic oxidative stress.

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.

Type 2 diabetes (T2DM) is characterized by well-preserved insulin secretion; however, the surrounding tissue is insensitive to insulin, resulting in increased blood glucose level due to the inability of tissues to convert glucose into energy. As a result of chronic non-regulation of glucose levels and high daily fluctuations in the blood, the micro- and macrovascular complications occur in these patients. Complications develop through two main mechanisms: induction of oxidative stress and innate immunity. In this regard, the aim of this study was to examine the effect of four week administration of DPP4 inhibitors (saxagliptin, sitagliptin and vildagliptin) to the parameters of oxidative stress and antioxidant defense in the group of rats with diabetes type 2 (T2DM). Sixty Wistar albino rats were divided randomly into 5 groups: group I: control healthy group; group II: rats with diabetes type 2; group III: rats with diabetes type 2 treated with 0.6 mg/kg of sitagliptin; group IV: rats with diabetes type 2 treated with 0.45 mg/kg of saxagliptin, group V: rats with diabetes type 2 treated with 9 mg/kg vildagliptin. The rats from experimental groups were fed with a high-fat diet for 4 weeks and after 6–8 h of starvation received one dose of streptozotocin (STZ) intraperitoneally (25 mg/kg body weight) to induce T2DM. Animals with fasting glucose above 7 mmol / L and insulin over 6 mmol / L were included in the study as rats with T2DM. Upon completion of the experiments, the blood was collected from the anesthetized animals and used for sphectrophotometrical determination of parameters of oxidative stress, and antioxidative defense. T2DM induced significant increase in production of reacitve oxygen species (ROS) (superoxide anion radical and hydrogen peroxide), but additional four-week administration of gliptins induced decrease in ROS values. On the other hand, T2DM induced decrease of nitric oxide, superoxide dismutase, catalaze, and reduced gluthation and concomitant therapy with gliptins induced increase of these parametars, suggesting significant antioxidant potential of this group of drugs.

This study investigated different dietary strategies, high-fat (HFd), or standard diet (Sd) alone or in combination with standardized Aronia melanocarpa extract (SAE), as a polyphenol-rich diet, and their effects on lipids and fatty acids (FA) in rats with metabolic syndrome (MetS). Wistar albino rats were randomly divided into two groups: healthy and rats with MetS, and then depending on dietary patterns on six groups: healthy rats fed with Sd, healthy rats fed with Sd and SAE, rats with MetS fed with HFd, rats with MetS fed with HFd and SAE, rats with MetS fed with Sd, and rats with MetS fed with Sd and SAE. 4 weeks later, after an overnight fast (12-14 h), blood for determination of total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), index of lipid peroxidation (measured as TBARS), and FA was collected. Increased FA and lipid concentration found in MetS rats were reduced when changing dietary habits from HFd to Sd with or without SAE consumption. Consumption of SAE slightly affects the FA profiles, mostly palmitoleic acid in healthy rats and PUFA in MetS + HFd rats. Nevertheless, in a high-fat diet, SAE supplementation significantly decreases n-6/n-3 ratio, thereby decreasing systemic inflammation. Further researches are warranted to confirm these effects in humans.

The main goal of this study was to investigate the cardioprotective properties in terms of effects on cardiodynamics of perfluorocarbon emulsion in ex vivo-induced ischemic-reperfusion injury of an isolated rat heart. The first part of the study aims to determine the dose of 10% perfluoroemulsion (PFT) that will show the best cardioprotective effect in rats on ex vivo-induced ischemic / reperfusion injury of an isolated rat heart. Depending on whether the animals received saline or PFT, the animals were divided into a control or experimental group, and depending on the application of a dose (8, 12, 16 ml / kg body weight) of saline or PFT. At a dose of 8 ml / kg, the results indicate statistically significantly lower values ​​of the maximum pressure growth rate in the group treated with 10% PFT compared to the control group treated with saline at R5 and R25 points. At a dose of 12 ml / kg, the maximum left ventricular pressure growth rate differed statistically significantly in the PFT group, ie there was an increase in this parameter at points R25 and R30, and the minimum left ventricular pressure growth rate in R15-R30 compared to saline-treated group. At a dose of 16 ml / kg, PFT also had a statistically significant effect on the change in cardiodynamic parameters in an isolated rat heart organ. Based on all the above, we can conclude that Peftoran administered immediately before ischemia (1 hour) has less positive effects on myocardial function in a model of an isolated rat heart compared to earlier administration (10 and 20 hours). Also, the effects of 10% peftoran solution are more pronounced if there is a longer period of time from application to ischemia, ie immediate application of peftoran before ischemia (1 hour) gave the weakest effects on the change of cardiodynamics of isolated rat heart.

The main goal of this study was to investigate the cardioprotective properties in terms of effects on cardiodynamics of perfluorocarbon emulsion (PFE) in ex vivo-induced ischemia-reperfusion injury of an isolated rat heart. The first part of the study aimed to determine the dose of 10% perfluoroemulsion (PFE) that would show the best cardioprotective effect in rats on ex vivo-induced ischemia-reperfusion injury of an isolated rat heart. Depending on whether the animals received saline or PFE, the animals were divided into a control or experimental group. They were also grouped depending on the applied dose (8, 12, 16 ml/kg body weight) of saline or PFE. We observed the huge changes in almost all parameters in the PFE groups in comparison with IR group without any pre-treatment. Calculated in percent, dp/dt max was the most changed parameter in group treated with 8 mg/kg, while the dp/dt min, SLVP, DLVP, HR, and CF were the most changed in group treated with 16 mg/kg 10 h before ischemia. The effects of 10% PFE are more pronounced if there is a longer period of time from application to ischemia, i.e., immediate application of PFE before ischemia (1 h) gave the weakest effects on the change of cardiodynamics of isolated rat heart. Therefore, the future of PFE use is in new indications and application methods, and PFE can also be referred to as antihypoxic and antiischemic blood substitute with mild membranotropic effects.

The aim of our study was to investigate the effects of one-month consumption of polyphenol-rich standardized Aronia melanocarpa extract (SAE) on redox status in anemic hemodialysis patients. The study included 30 patients (Hb 3 months; > 3 times week). Patients were treated with commercially available SAE in a dose of 30 ml/day, for 30 days. After finishing the treatment blood samples were taken in order to evaluate the effects of SAE on redox status. Several parameters of anemia and inflammation were also followed. After the completion of the treatment, the levels of superoxide anion radical and nitrites significantly dropped, while the antioxidant capacity improved via elevation of catalase and reduced glutathione. Proven antioxidant effect was followed by beneficial effects on anemia parameters (increased hemoglobin and haptoglobin concentration, decreased ferritin and lactate dehydrogenase concentration), but SAE consumption didn`t improve inflammatory status, except for minor decrease in C-reactive protein. The consumption of SAE regulates redox status (reduce the productions of pro-oxidative molecules and increase antioxidant defense) and has beneficial effects on anemia parameters. SAE could be considered as supportive therapy in patients receiving hemodialysis which are prone to oxidative stress caused by both chronic kidney disease and hemodialysis procedure. Additionally, it could potentially be a good choice for supplementation of anemic hemodialysis patients. TRN: NCT04208451 December 23, 2019 “retrospectively registered”

This study aimed to examine the effects of diallyl trisulfide (DATS), the most potent polysulfide derived from garlic, on metabolic syndrome and myocardial function in rats with metabolic syndrome (MetS). For that purpose, we used 36 male Wistar albino rats divided into control rats, rats with MetS and MetS rats treated with 40 mg/kg of DATS every second day for 3 weeks. In the first part, we studied the impact of DATS on MetS control and found that DATS significantly raised H2S, decreased homocysteine and glucose levels and enhanced lipid and antioxidative, while reducing prooxidative parameters. Additionally, this polysulfide improved cardiac function. In the second part, we investigated the impact of DATS on ex vivo induced ischemia/reperfusion (I/R) heart injury and found that DATS consumption significantly improved cardiodynamic parameters and prevented oxidative and histo-architectural variation in the heart. In addition, DATS significantly increased relative gene expression of eNOS, SOD-1 and -2, Bcl-2 and decreased relative gene expression of NF-κB, IL-17A, Bax, and caspases-3 and -9. Taken together, the data show that DATS can effectively mitigate MetS and have protective effects against ex vivo induced myocardial I/R injury in MetS rat.

Ruthenium(II) complexes offer the potential for lower toxicity compared with platinum(II) complexes. Our study aimed to compare cardiotoxicity of [Ru(Cl-tpy)(en)Cl][Cl], [Ru(Cl-tpy)(dach)Cl][Cl], [Ru(Cl-tpy)(bpy)Cl][Cl], cisplatin, and saline through assessment of redox status and relative expression of apoptosis-related genes. A total of 40 Wistar albino rats were divided into five groups. Ruthenium groups received a single dose of complexes intraperitoneally (4 mg/kg/week) for a 4-week period; cisplatin group received cisplatin (4 mg/kg/week) and control group received saline (4 mL/kg/week) in the same manner as ruthenium groups. In collected blood and heart tissue samples, spectrophotometric determination of oxidative stress biomarkers was performed. The relative expression of apoptosis-related genes (Bcl-2, Bax, and caspase-3) in hearts was examined by real-time polymerase chain reaction. Our results showed that systemic and cardiac pro-oxidative markers (thiobarbituric acid reactive substances and nitrite) were significantly lower in ruthenium groups compared with cisplatin group, while concentrations of antioxidative parameters (catalase, superoxide dismutase, and oxidized glutathione) were significantly higher. Ruthenium administration led to significantly lower gene expression of Bax and caspase-3 compared with cisplatin-treated rats, while Bcl-2 remained unchanged. Applied ruthenium complexes have less pronounced potential for induction of oxidative stress-mediated cardiotoxicity compared with cisplatin. These findings may help for future studies that should clarify the mechanisms of cardiotoxicity of ruthenium-based metallodrugs.

As well as the most known role of N-methyl-D-aspartate receptors (NMDARs) in the nervous system, there is a plethora of evidence that NMDARs are also present in the cardiovascular system where they participate in various physiological processes, as well as pathological conditions. The aim of this study was to assess the effects of preconditioning and postconditioning of isolated rat heart with NMDAR agonists and antagonists on heart function and release of oxidative stress biomarkers. The hearts of male Wistar albino rats were subjected to global ischemia for 20 min, followed by 30 min of reperfusion, using the Langendorff technique, and cardiodynamic parameters were determined during the subsequent preconditioning with the NMDAR agonists glutamate (100 &micro, mol/L) and (RS)-(Tetrazol-5-yl)glycine (5 &mu, mol/L) and the NMDAR antagonists memantine (100 &mu, mol/L) and MK-801 (30 &mu, mol/L). In the postconditioning group, the hearts were perfused with the same dose of drugs during the first 3 min of reperfusion. The oxidative stress biomarkers were determined spectrophotometrically in samples of coronary venous effluent. The NMDAR antagonists, especially MK-801, applied in postconditioning had a marked antioxidative effect with a most pronounced protective effect. The results from this study suggest that NMDARs could be a potential therapeutic target in the prevention and treatment of ischemic and reperfusion injury of the heart.

This research is designed to test the hypothesis that elevated homocysteine (Hcy) levels in vivo, caused by a deficit in vitamin B complex, promote changes in cardiac function and redox status that lead to heart failure. In order to conduct the study, we used adult male Wistar albino rats (n = 30; 4 weeks old; 100 ± 15 g body weight). Hyperhomocysteinaemia (HHcy) in these animals was achieved by dietary manipulation. For 4 weeks, the animals were fed with a standard rodent chow (control, CF), a diet enriched in methionine with no deficiency in B vitamins (i.e., folic acid, B6 and B12) (HMNV) or a diet enriched in methionine and deficient in B vitamins (HMLV). After 28 days of dietary manipulation, all animals were killed. The rat hearts were isolated and retrogradely perfused according to the Langendorff technique at a gradually increasing perfusion pressure. We found a negative correlation between elevated serum Hcy and total body and heart weight. The maximum rate of left ventricular pressure development was significantly increased in the HMNV group compared with in the other groups. Systolic left ventricular pressure was significantly changed in all groups. HHcy induces remodelling of the cardiac tissues, as moderate HHcy is associated with more prominent interstitial and perivascular fibrosis. Our results suggest that a high methionine diet without vitamin B complex causes profound negative effects associated with HHcy.

It has been assumed that the cardioprotective effects of propofol are due to its non-anesthetic pleiotropic cardiac and vasodilator effects, in which gasotransmitters (NO, H2S, and CO) as well as calcium influx could be involved. The study on isolated rat heart was performed using 4 experimental groups (n = 7 in each): (1) bolus injection of propofol (100 mg/kg body mass, i.p.); (2) L-NAME (NO synthase inhibitor, 60 mg/kg body mass, i.p.) + propofol; (3) DL-PAG (H2S synthase inhibitor, 50 mg/kg body mass, i.p.) + propofol; (4) ZnPPIX (CO synthase inhibitor, 50 μmol/kg body mass, i.p.) + propofol. Before and after the verapamil (3 μmol/L) administration, cardiodynamic parameters were recorded (dp/dtmax, dp/dtmin, systolic left ventricular pressure, diastolic left ventricular pressure, heart rate, coronary flow), as well as coronary and cardiac oxidative stress parameters. The results showed significant increases of diastolic left ventricular pressure following NO and CO inhibition, but also increases of coronary flow following H2S and CO inhibition. Following verapamil administration, significant decreases of dp/dtmaxwere noted after NO and CO inhibition, then increase of diastolic left ventricular pressure following CO inhibition, and increase of coronary flow following NO, H2S, or CO inhibition. Oxidative stress markers were increased but catalase activity was significantly decreased in cardiac tissue. Gasotransmitters and calcium influx are involved in pleiotropic cardiovascular effects of propofol in male Wistar rats.

The aim of the present study was to compare the cardiodynamic parameters in the isolated rat heart in animals chronically treated with cisplatin, platinum(IV) complex and its diamine ligand. Sixty Wistar albino rats (8 weeks old) were divided into five groups: three experimental and two control groups. Animals in all groups were treated with a dose of 4 mg/kg body weight once a week for 4 weeks with different substances; experimental groups received cisplatin, ligand and octahedral platinum(IV) complex, and control groups received saline and dimethyl sulfoxide. After sacrificing the animals, hearts were isolated and perfused according to the Langendorff technique at gradually increased coronary perfusion pressures (40–120 cmH2O). The following parameters of cardiac function were continuously recorded: maximum and minimum rate of change of pressure in the left ventricle, systolic and diastolic left ventricular pressure, heart rate and coronary flow. The results showed statistically significant differences between all experimental groups in maximum and minimum rate of pressure development as well as in systolic pressure of the left ventricle, whereas cisplatin, ligand and the platinum(IV) complex had effects on heart contractility without significant influences on coronary circulation. The findings of the present study could be important for a better understanding of anticancer drug cardiac side effects. Our results indicate that compared to cisplatin as a “gold standard”, novel platinum complexes and ligands do not possess fewer negative effects on the heart, indicating insufficient safety for their usage in terms of affecting cardiac function, a result that can be of great interest for further investigations.

The aim of this study was to examine and compare the effects of the acute administration of verapamil or amlodipine as representatives of the calcium channel blockers or nicorandil as a representative of the mitochondrial ATP-dependent potassium (KATP) channel opener to cardiac contractility, coronary flow, and oxidative stress markers on ischemia/reperfusion injury in the isolated rat heart. The hearts of adult male Wistar albino rats (n = 60 total, 12 per group) were divided into five groups, two controls (preconditioning with Krebs–Henseleit solution) and three experimental depending on acute administrated pharmacological agents (0,63 µmol/L of verapamil, 0,1 µmol/L of amlodipine, and 200 µmol/L of nicorandil). After stabilization and 5 min of preconditioning in experimental groups, hearts from I/R control and all experimental groups underwent global ischemia (20 min) and reperfusion (30 min). Hearts from sham group were continuously followed for 50 min, after stabilization period. Cardiodynamic parameters and coronary flow were recorded at the end of stabilization (S), at the last minute of pharmacological preconditioning (P) and at intervals of 5 min after global ischemia, during reperfusion, or in case of sham group during 20–50 min after stabilization. At the same intervals, we collected coronary venous effluent from which we spectrophotometrically measured the parameters of oxidative stress: the index of lipid peroxidation, superoxide anion radical, hydrogen peroxide, and nitrite. In summary, our findings clearly indicate that the blocking of the calcium channel or the activation of KATP may mediate the protective effect of myocardial preconditioning. The ex vivo results showed that all examined drugs after ischemia and reperfusion have beneficial cardioprotective properties associated with lower values of major pro-oxidative molecules. Obtained effects seem to be the most convincible in case of nicorandil.

The aim of present study was to evaluate the effects of 3- and 6-week swimming exercise on cardiodynamics and coronary flow in high salt-induced hypertensive and normotensive rats. 80 male Wistar albino rats (6 weeks old) were divided into 8 groups: hypertensive animals that swam for 3 weeks; hypertensive animals that swam for 6 weeks and their respective sedentary controls; normotensive animals that swam for 3 weeks; normotensive animals that swam for 6 weeks and their respective sedentary controls. Hypertensive animals were on high sodium (8% NaCl solution) diet for 4 weeks, and these animals did not drink tap water during the experimental protocol. After sacrificing, hearts were isolated and perfused according to Langendorff technique at gradually increased coronary perfusion pressure (40–120 cmH2O). The following parameters of cardiac function were continuously recorded: maximum and minimum rate of pressure development in LV, systolic, and diastolic left ventricular pressure, and heart rate. Coronary flow was measured flowmetrically. Findings of the present study may help in better understanding of short- to medium-term exercise-induced direct effects on cardiac function and perfusion. Generally viewed, swimming of both durations did not change myocardial function and perfusion in hypertensive and normotensive conditions.

The aim of our study was to examine the effects of different dietary strategies, high-fat (HFd) or standard diet (Sd) alone or in combination with standardized oral supplementation (0.45 mL/kg/day) of Aronia melanocarpa extract (SAE) in rats with metabolic syndrome (MetS). SAE is an official product of pharmaceutical company Pharmanova (Belgrade, Serbia), however, the procedure for extraction was done by EU-Chem company (Belgrade, Serbia). Rats were divided randomly into six groups: control with Sd, control with Sd and SAE, MetS with HFd, MetS with HFd and SAE, MetS with Sd and MetS with Sd and SAE during 4 weeks. At the end of the 4-week protocol, cardiac function and liver morphology were assessed, while in the blood samples glucose, insulin, iron levels and systemic redox state were determined. Our results demonstrated that SAE had the ability to lower blood pressure and exert benefits on in vivo and ex vivo heart function. Moreover, SAE improved glucose tolerance, attenuated pathological liver alterations and oxidative stress present in MetS. Obtained beneficial effects of SAE were more prominent in combination with changing dietary habits. Promising potential of SAE supplementation alone or in combination with different dietary protocols in triggering cardioprotection should be further examined in future.