The impact of different diuretics on regression of myocardial reperfusion injury in spontaneously hypertensive rats.

The study's objective was to ascertain the results of sub-chronic therapy of various diuretics on the ischemia/reperfusion dysfunction of the heart in hypertensive rats by a global ischemia in an isolated rat heart model. The research included 40 spontaneously hypertensive male rats (Wistar Kyoto strain, body mass 250 ± 30 g, 8 weeks old) grouped into four groups. The animals were treated for 4 weeks with 10 mg/kg of hydrochlorothiazide, indapamide, or spironolactone per os. After a period of sub-chronic treatment, we analyzed hemodynamic measurements, echocardiography, and myocardial function according to the Langendorff retrograde perfusion method. The hearts were subjected to 20 min of global ischemia and then reperfused for 30 min (I20:R30). Cardiovascular parameters that depict the left ventricle functions were continuously monitored, while flowmetry was used to determine coronary flow values. Markers of oxidative stress were estimated from coronary venous effluent using spectrophotometry. All three examined diuretics (hydrochlorothiazide, spironolactone, indapamide) lowered the production of the majority of the detected prooxidants, reducing myocardial oxidative damage. The cardiological examination of heart function in vivo demonstrated that treatment with indapamide and spironolactone mitigates left ventricular hypertrophy but without significant lowering of blood pressure or increment in ejection fraction. Additionally, monitoring of cardiac function ex vivo indicated the cardiodepressant effect of spironolactone in spontaneously hypertensive rats.

Sacubitril/valsartan reverses cardiac structure and function in experimental model of hypertension-induced hypertrophic cardiomyopathy.

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 healthy (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 groups. Myocardial structure and function were assessed using echocardiography, Langendorff's isolated heart experiment, blood sampling and qualitative polymerase chain reaction. Echocardiographic examinations revealed protective effects of sacubitril/valsartan by improving left ventricular internal diameter in systole and diastole and fractional shortening. Additionally, sacubitril/valsartan treatment decreased systolic and diastolic blood pressures in comparison with untreated hypertensive rats. Moreover, sacubitril/valsartan treatment reduced oxidative stress and apoptosis (reduced expression of Bax and Cas9 genes) compared to untreated rats. There was a regular histomorphology of cardiomyocytes, interstitium, and blood vessels in treated rats compared to untreated HpCM rats which expressed hypertrophic cardiomyocytes, with polymorphic nuclei, prominent nucleoli and moderately dilated interstitium. In experimental model of hypertension-induced hypertrophic cardiomyopathy, sacubitril/valsartan treatment led to improved cardiac structure, haemodynamic performance, and reduced oxidative stress and apoptosis. Sacubitril/valsartan thus presents as a potential therapeutic strategy resulted in hypertension-induced hypertrophic cardiomyopathy.

The Enhanced Effects of Swimming and Running Preconditioning in an Experimental Model of Myocardial Ischemia/Reperfusion Injury.

Background and Objectives: This study was conducted to examine the influence of different swimming and running protocols as forms of physiological preconditioning on an isolated rat heart's ischemia/reperfusion injury. Materials and Methods: This study was conducted on 60 male Wistar albino rats (6 weeks old, bw: 200 ± 20 g), divided into: CTRL group-a sedentary control group; sAeT-a group that underwent aerobic swimming conditioning using a swimming protocol for 8 weeks; sAnT-a group that underwent anaerobic swimming conditioning; rAeT-a group that underwent aerobic running conditioning; and rAnT-a group that underwent anaerobic running conditioning. After the preconditioning protocols, ex vivo estimating of myocardial function according to the Langendorff technique was performed. Results: The anaerobic running training decreased heart rate and the anaerobic swimming training reduced coronary flow, demonstrating the difference in the physiological heart response of aerobic/anaerobic physical training (p < 0.05). Heart rate was significantly reduced in both training swimming groups after a period of ischemia (p < 0.05). On the other hand, the anaerobic running protocol induced a significantly decreased heart rate in comparison with the aerobic running group and the sedentary group (p < 0.05). Conclusions: The data from this experimental study support many protective training effects, i.e., improved contractility, improved resting heart rate, and increased physical work capacity and exercise tolerance. Physical training in the form of anaerobic running induces greater heart preconditioning for reperfusion injury in comparison with anaerobic swimming training.

SGLT2 inhibitors: a focus on cardiac benefits and potential mechanisms.

This paper highlights the cardioprotective potential of sodium-glucose cotransporter 2 inhibitors (SLGT2i), as well as several most discussed mechanisms responsible for their cardioprotection. Cardiovascular diseases are considered a primary cause of death in nearly 80% of type 2 diabetes mellitus (T2DM) patients, with a 2-4-fold greater incidence of heart failure (HF) among diabetics. As novel hypoglycemics, SGLT2i showed exceptional cardiovascular benefits, reflected through robust reductions of cardiovascular mortality and hospitalization for HF in T2DM patients. Recently, those effects have been reported even in patients with HF and reduced ejection fraction irrespectively of diabetic status, suggesting that cardioprotective effects of SGLT2i are driven independently of their hypoglycemic actions. SGLT2i exerted hemodynamic and metabolic effects, partially driven by natriuresis and osmotic diuresis. However, those systemic effects are modest, and therefore cannot be completely related to the cardiac benefits of these agents in T2DM patients. Hence, increased circulating ketone levels during SGLT2i administration have brought out another hypothesis of a cardiac metabolic switch. Moreover, SGLT2i influence ion homeostasis and exert anti-inflammatory and antifibrotic effects. Their enviable influence on oxidative stress markers, as well as anti- and pro-apoptotic factors, have also been reported. However, since the main mechanistical contributor of their cardioprotection has not been elucidated yet, a joint action of systemic and molecular mechanisms has been suggested. In the light of ongoing trials evaluating the effects of SGLT2i in patients with HF and preserved ejection fraction, a new chapter of beneficial SGLT2i mechanisms is expected, which might resolve their main underlying action.

Dose-dependent effects of perfluorocarbon-based blood substitute on cardiac function in myocardial ischemia-reperfusion injury.

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.

Creatine phosphate administration in cardiac ischemia-reperfusion injury in rats: focus on differences between preconditioning, perconditioning, and postconditioning protocols.

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 +(dP/dt max) and 97.61% for -(dP/dt max), in Per group 96.72% for +(dP/dt max) and 95.60% for -(dP/dt max), and in Post group 143.84% for +(dP/dt max) and 104.36% for -(dP/dt 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.

Guanidinoacetic acid provides superior cardioprotection to its combined use with betaine and (or) creatine in HIIT-trained rats.

This study aimed to determine how guanidinoacetic acid (GAA) or its combined administration with betaine (B) or creatine (C) influences the cardiac function, morphometric parameters, and redox status of rats subjected to high-intensity interval training (HIIT). This research was conducted on male Wistar albino rats exposed to HIIT for 4 weeks. The animals were randomly divided into five groups: HIIT, HIIT + GAA, HIIT + GAA + C, HIIT + GAA + B, and HIIT + GAA + C + B. After completing the training protocol, GAA (300 mg/kg), C (280 mg/kg), and B (300 mg/kg) were applied daily per os for 4 weeks. GAA supplementation in combination with HIIT significantly decreased the level of both systemic and cardiac prooxidants ( O 2 - , H2O2, NO 2 - , and thiobarbituric acid reactive substances) compared with nontreated HIIT (p < 0.05). Also, GAA treatment led to an increase in glutathione and superoxide dismutase levels. None of the treatment regimens altered cardiac function. A larger degree of cardiomyocyte hypertrophy was observed in the HIIT + GAA group, which was reflected through an increase of the cross-sectional area of 27% (p < 0.05) and that of the left ventricle wall thickness of 27% (p < 0.05). Since we showed that GAA in combination with HIIT may ameliorate oxidative stress and does not alter cardiac function, the present study is a basis for future research exploring the mechanisms of cardioprotection induced by this supplement in an HIIT scenario.

Effects of Combined Allogenic Adipose Stem Cells and Hyperbaric Oxygenation Treatment on Pathogenesis of Osteoarthritis in Knee Joint Induced by Monoiodoacetate.

The beneficial effects of HBO in inflammatory processes make it an attractive type of treatment for chronic arthritis. In addition, the effects of combination therapy based on adipose stem cells and HBO on OA progression have not been fully investigated. The current study explored the efficacy of intra-articular injection of allogeneic adipose-derived mesenchymal stem cells (ADMSCs) combined with hyperbaric oxygenation treatment (HBO) in a rat osteoarthritis (OA) model. The rat OA model was induced by intra-articular injection of monoiodoacetate (MIA) and 7 days after application of MIA rats were divided into five groups: healthy control (CTRL), osteoarthritis (OA), ADMSCs (ADS), the HBO+ADS21day and HBO+ADS28day groups. A single dose of 1 × 106 allogeneic ADMSCs suspended in sterile saline was injected into the knee joint alone or in combination with HBO treatment. Rats were sacrificed at 3 or 4 weeks after MIA injection. Treatment outcomes were evaluated by radiographic, morphological and histological analysis and by specific staining of articular cartilage. We also measured the level of inflammatory and pro/antioxidative markers. We confirmed that combined treatment of ADMSCs and HBO significantly improved the regeneration of cartilage in the knee joint. Rtg score of knee joint damage was significantly decreased in the HBO+ADS21day and HBO+ADS28day groups compared to the OA. However, the positive effect in the HBO+ADS28day group was greater than the HBO+ADS21day group. The articular cartilage was relatively normal in the HBO+ADS28day group, but moderate degeneration was observed in the HBO+ADS21day compared to the OA group. These findings are in line with the histopathological results. A significantly lower level of O2-. was observed in the HBO+ADS28day group but a higher NO level compared to the HBO+ADS21day group. Moreover, in the HBO+ADS28day group significantly higher concentrations of IL-10 were observed but there was no significant difference in proinflammatory cytokine in serum samples. These results indicate that a single intra-articular injection of allogeneic ADMSCs combined with HBO efficiently attenuated OA progression after 28 days with greater therapeutic effect compared to alone ADMSCs or after 3 weeks of combined treatment. Combined treatment might be an effective treatment for OA in humans.

The Evaluation of Healing Properties of Galium verum-Based Oral Gel in Aphthous Stomatitis in Rats.

Although oral ulcers represent one of the most frequent oral mucosal diseases, the available treatment is not sufficient to provide complete ulcer recovery without side-effects. Therefore, the aim of our study was to prepare a mucoadhesive oral gel based on Galium verum ethanol extract (GVL gel) and reveal its healing effects in the model of aphthous stomatitis in rats. Rats with oral ulcers were divided into the following groups: control (untreated), gel base (ulcer was treated with the gel base, three times per day for 10 days), and GVL gel group (the ulcer was treated with GVL gel in the same way as the gel base). Animals from each group were sacrificed on days 0, 3, 6, and 10 for collecting blood and ulcer tissue samples. Healing properties of oral gel were determined by clinical evaluation, as well as biochemical and histopathological examinations. Our findings suggest a significant decrease in the ulcer size in GVL gel group, with healing effects achieved through the alleviation of oxidative stress, reduction in COX-2 immunopositivity, and increase in collagen content in buccal tissue. Significant ulcer repairing potential of GVL gel highlights this oral mucoadhesive gel as a promising tool for prevention and treatment of RAS.

Dipeptidyl peptidase-4 inhibitors as new tools for cardioprotection.

Previous studies have demonstrated that individuals with type 2 diabetes mellitus (T2DM) have a two- to fourfold propensity to develop cardiovascular disease (CVD) than nondiabetic population, making CVD a major cause of death and disability among people with T2DM. The present treatment options for management of diabetes propose the earlier and more frequent use of new antidiabetic drugs that could control hyperglycaemia and reduce the risk of cardiovascular events. Findings from basic and clinical studies pointed out DPP-4 inhibitors as potentially novel pharmacological tools for cardioprotection. There is a growing body of evidence suggesting that these drugs have ability to protect the heart against acute ischaemia-reperfusion injury as well as reduce the size of infarction. Consequently, the prevention of degradation of the incretin hormones by the use of DPP-4 inhibitors represents a new strategy in the treatment of patients with T2DM and reduction of CV events in these patients. Here, we discuss the cardioprotective effects of DPP-4 inhibitors as well as proposed pathways that these hypoglycaemic agents target in the cardiovascular system.

The influence of acclimatization on stress hormone concentration in serum during heat stress.

This study was aimed to examine the influence of acclimatization on the change of concentration of stress hormones in men's serum exposed to heat stress during physical training. The study included a total of 40 men, aged 19-21 years, divided randomly into four groups: CTRL group: control, exposed to the Exercise Tolerance Testing in comfortable conditions; O group: exposed to Exercise Tolerance Testing in a warm environment; P group: exposed to passive acclimation to heat for 10 days, followed by Exercise Tolerance Testing in a warm environment; A group: exposed to active acclimation to heat for 10 days, followed by Exercise Tolerance Testing in a warm environment. All participants were tested for thermoregulation and acclimatization, skin and tympanic temperature, heart rate (HR), hormonal status and sweating. The mean skin temperature was the lowest in the control group of subjects exposed to physical exertion under comfortable conditions, and at each point of measurement it was statistically significantly different from that of the other study groups (p < 0.001). Sweating intensity was statistically significantly the lowest in the CTRL group (0.32 ± 0.04 l/m2/h; p < 0.001), compared to all other groups. Cortisol was significantly altered in O group (632.2 ± 92.3; 467.2 ± 89.7), testosterone levels were significantly altered in P (19.2 ± 9.3; 16.4 ± 7.3) and in A groups (22.1 ± 12.4; 14.9 ± 9.9), while prolactin was changed in O (392.1 ± 51.3; 181.4 ± 42.3), P (595.1 ± 191.1; 191.2 ± 52.5), and A group (407.4 ± 189.3; 173.4 ± 43.9) after the experimental period. The impact of acclimatization on hormonal indicators emphasizes its importance in the response of the endocrine system of soldiers to perform military activities in warm climates.

Standardized Aronia melanocarpa extract regulates redox status in patients receiving hemodialysis with anemia.

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 < 110 g/l, hemodialysis or hemodiafiltration > 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 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".

Black chokeberry Aronia melanocarpa extract reduces blood pressure, glycemia and lipid profile in patients with metabolic syndrome: a prospective controlled trial.

The aim of the study was to examine the effect of 4-week supplementation of Alixir 400 PROTECT® (Standardized Aronia L. Melanocarpa Extract Extract-SAE) on clinical and biochemical parameters in patients with confirmed metabolic syndrome (MetS). This study was designed as a prospective open-label clinical case-series study with 28 days of follow-up with cases selected and followed during the period from February 1, 2018 to November 2019. The study included 143 male and female patients with MetS who were subjected to SAE. SAE supplementation significantly altered SP, BP as well as HR values. After 2 weeks, CHOL levels significantly decreased in the fMetS-DM group compared to the baseline values in this group, while the LDL levels significantly decreased in the fMetS group. Triglycerides significantly decreased only after 4 weeks of SAE treatment in diabetic groups of patients (fMetS-DM and mMetS-DM) compared to the baseline, while in non-diabetic groups this marker was not significantly altered. Increased polyphenols or SAE consumption is correlated with a positive effect on body weight, total cholesterol, low and high-density lipoproteins, blood pressure and glycemia. Increasing consumption of polyphenol-rich foods could be a promising strategy to reduce cardiovascular risk.

Early predictive blood markers of hemorrhagic stroke - influence of cytoflavin therapy.

Examination of the patterns of free-radical processes (FRP) and changes of the early screening markers to predict the course of hemorrhagic stroke (HS) and applied pathophysiologically based therapy can be of great practical importance. This study aimed to determine early changes in the parameters of oxidative stress and routine biochemistry blood tests in patients with HS and to assess their relationship with clinical outcome. The effects of early applied cytoflavin were also investigated. The prospective study included 151 patients with HS. Forty-eight percent of patients in the standard conservative therapy were given cytoflavin antioxidant energy therapy from the first day of hospitalization. The neurological status, neuroimaging, biochemical blood tests and FRP were assessed on days 1, 5, 10, and 20 of hospitalization. In patients with HS, an imbalance of all stages of FRP was detected proportionately to the severity of HS. The malondialdehyde concentration above 5.3 µmol/L, the number of leukocytes above 15 800, glucose above 11.9 mmol/L, lactate dehydrogenase above 574 IU/L, and lactate above 2.5 mmol/L, detected on the first day, predetermined a high risk of death. Additional cytoflavin treatment allowed stabilizing the clinical laboratory picture of HS, improved the treatment results, and reduced hospital mortality rate.

The role of aldosterone inhibitors in cardiac ischemia-reperfusion injury.

Myocardial ischaemia-reperfusion (I/R) injury is a well-known term for exacerbation of cellular destruction and dysfunction after the restoration of blood flow to a previously ischaemic heart. A vast number of studies that have demonstrated that the role of mineralocorticoids in cardiovascular diseases is based on the use of pharmacological mineralocorticoid receptor (MR) antagonists. This review paper aimed to summarize current knowledge on the effects of MR antagonists on myocardial I/R injury as well as postinfarction remodeling. Animal models, predominantly the Langendorff technique and left anterior descending coronary artery occlusion, have confirmed the potency of MR antagonists as preconditioning and postconditioning agents in limiting infarct size and postinfarction remodeling. Several preclinical studies in rodents have established and proved possible mechanisms of cardioprotection by MR antagonists, such as reduction of oxidative stress, reduction of inflammation, and apoptosis, therefore limiting the infarct zone. However, the results of some clinical trials are inconsistent, since they reported no benefit of MR antagonists in acute myocardial infarction. Due to this, further studies and the results of ongoing clinical trials regarding MR antagonist administration in patients with acute myocardial infarction are being awaited with great interest.

The influences of chokeberry extract supplementation on redox status and body composition in handball players during competition phase.

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.

Redox and apoptotic potential of novel ruthenium complexes in rat blood and heart.

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.

Dipeptidyl peptidase 4 inhibitors attenuate cardiac ischaemia-reperfusion injury in rats with diabetes mellitus type 2.

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.

Cardiac, biochemical and histopathological analysis reveals impaired heart function in hypertensive rats with apical periodontitis.

AIM: To investigate the association between experimentally induced apical periodontitis (AP) and heart function in hypertensive rats. METHODOLOGY: Forty-eight normotensive Wistar albino and spontaneously hypertensive (SHR) rats were divided into four equal groups: control (C), normotensive with AP (AP), SHR and SHR with AP (SHR + AP). AP was induced on the first right mandibular molars by exposing the pulp chambers to the oral environment for four weeks and confirmed radiographically. Thereafter, the animals were sacrificed by cervical dislocation, whilst hearts were isolated and perfused according to the Langendorff technique gradually increasing coronary perfusion pressures 40-120 cmH2 O. The hemimandibles were analysed radiographically (mm2 and pixels) to verify the presence of AP. Biomarkers of cardiac oxidative stress (OS) were determined in coronary venous effluent and cardiac tissue homogenate. Cardiac tissue was analysed histopathologically for signs of heart damage (oedema, fibrosis and necrosis). All data were analysed by Kruskal-Wallis and one-way anova tests (p < .05). RESULTS: The levels of the maximum left ventricular pressure development rate of the SHR + AP group were significantly increased compared to the AP and C groups, and of the SHR group compared with the C group (p < .05). The levels of the minimum left ventricular pressure development rate of the SHR + AP group were significantly decreased compared to the AP, SHR and C groups, and of the SHR group compared to the C group (p < .05). The radiographic AP area was significantly larger in the SHR + AP group than in the AP group (p < .01). The levels of superoxide anion were significantly higher in the SHR + AP group than in the AP, SHR and C groups (p < .05). The activities of superoxide dismutase in cardiac tissue homogenate were significantly lower in the SHR + AP and AP groups compared with the SHR and C groups (p < .05). CONCLUSIONS: In rats, AP was associated with impaired cardiodynamics, disturbed cardiac OS, antioxidant defence and cardiac pathologic changes in hypertensive conditions. Hypertension was associated with an increase in the AP radiographic area. Further studies should confirm whether root canal treatment can have a cardioprotective effect and reduce cardiac OS in hypertensive conditions.

Flaxseed and evening primrose oil slightly affect systolic and diastolic function of isolated heart in male but not in female rats.

Considering that sex related differences in cardiac response to flaxseed (FSO) and evening primrose oil (EPO) are insufficiently known present investigation assessed the effect of these two oils, on the cardiac function of isolated rat hearts and the possible role of sex in this. The present study was carried out on 60 adult male Wistar albino rats randomly divided into 6 groups: male rats treated with EPO, dose of 10 mg/kg/day; female rats treated with EPO, dose of 10 mg/kg/day; male rats treated with FSO, dose of 300 mg/kg/day; female rats treated with FSO, dose of 300 mg/kg/day; control group of female rats treated with regular laboratory diet for animals; control group of male rats treated with regular laboratory diet for animals. Using the Langendorff technique, markers of the heart function were evaluated: the maximum and minimum rates of pressure development in the left ventricle (LV; dP/dtmax, dP/dtmin), systolic and diastolic left ventricular pressure (SLVP, DLVP, respectively), heart rate (HR) and coronary flow (CF). Male rats treated with EPO had significantly higher (p = 0.016) mean values of dP/dtmax, dP/dtmin, SLVP and DLVP (average increase for all CPPs 20%, 25%, 30% and 110%, respectively), compared to the group of male rats treated with FSO (p = 0.914). Our study results indicate that both types of PUFA oils only slightly changed the function of the isolated rat heart in male but not in female rats. Nevertheless, the difference between oil treatments was found in male rats who had stronger cardiac response after supplementation with EPO.