A common oral pathogen Porphyromonas gingivalis induces myocarditis in rats.

AIM: To evaluate whether Porphyromonas gingivalis (P. gingivalis) inoculation could induce cardiac remodelling in rats. MATERIALS AND METHODS: The study was conducted on 33 Wistar rats, which were distributed in the following experimental groups: not inoculated; inoculated with 1 × 108 CFU/ml of bacteria; inoculated with 3 × 108 CFU/ml of bacteria. The animals were inoculated at baseline and on the 15th day of follow-up. Blood collection was performed at baseline and 60 min after each inoculation. At 29 days, the animals were subjected to echocardiography and at 30 days to haemodynamic studies before sacrificing them. RESULTS: Impact of the bacteria was more evident in rats that received higher P. gingivalis concentration. Thus, 3 × 108 CFU/ml of bacteria increased the rectal temperature and water content in the lung as well as myocardial necrosis and fibrosis. P. gingivalis induced the intensification of DNA fragmentation and increased the levels of malondialdehyde, oxidized proteins, and macrophage expression in the myocardium. These findings were associated with lower LV isovolumetric relaxation time, +dP/dt, -dP/dt, and higher end-diastolic pressure. CONCLUSIONS: P. gingivalis bacteraemia is significantly associated with adverse cardiac remodelling and may play a biological role in the genesis of heart failure.

Post-resistance exercise photobiomodulation therapy has a more effective antioxidant effect than pre-application on muscle oxidative stress.

This study evaluated the effect of photobiomodulation therapy (PBMt) before or after a high-intensity resistance exercise (RE) session on muscle oxidative stress. Female Wistar rats were assigned to one of the following groups: Sham (non-exercised, undergoing placebo-PBMt); NLRE (exercised, undergoing placebo-PBMt); PBMt + RE (pre-exercise PBMt); RE + PBMt (post-exercise PBMt). The RE comprised four climbs bearing the maximum load with a 2 min rest between each climb. An 830-nm aluminum gallium arsenide diode laser (100 mW; 0.028 cm2; 3.57 mW/cm2; 142.8 J/cm2; 4 J; Photon Laser III, DMC, São Paulo, Brazil) was applied 60 s before or after RE in gastrocnemius muscles. Analyses were performed at 24 h after RE: lipoperoxidation using malondialdehyde (MDA) and protein oxidation (OP) on Western blot. Superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activity were spectrophotometrically assessed. Nitric oxide (NO) level was determined by the Griess reaction. The MDA and OP levels were significantly higher in the NLRE group. Increased OP was prevented in all PBMt groups; however, increased MDA was prevented only in the RE + PBMT group. The RE + PBMt group had higher SOD activity compared to all other groups. A higher GPx activity was observed only in the PBMT + RE compared to Sham group, and CAT activity was reduced by RE, without PBMt effect. NO levels were unchanged with RE or PBMt. Therefore, PBMt application after a RE section has a more potent antioxidant effect than previous PBMt. Rats submitted to post-RE PBMt illustrated prevention of increased lipoperoxidation and protein oxidation as well as increased SOD activity. The photobiomodulation can attenuate oxidative stress induced by resistance exercise. A more evident benefit shows to be obtained with the application after exercise, in which it has increased the activity of superoxide dismustase.

Photobiomodulation Therapy on Myocardial Infarction in Rats: Transcriptional and Posttranscriptional Implications to Cardiac Remodeling.

BACKGROUND AND OBJECTIVES: Induction of myocardial infarction (MI) in rats by occlusion of the left anterior descending coronary artery is an experimental model used in research to elucidate functional, structural, and molecular modifications associated with ischemic heart disease. Photobiomodulation therapy (PBMT) has become a therapeutic alternative by modulating various biological processes eliciting several effects, including anti-inflammatory and pro-proliferative actions. The main objective of this work was to evaluate the effect of PBMT in the modulation of transcriptional and post-transcriptional changes that occurred in myocardium signal transduction pathways after MI. STUDY DESIGN/MATERIALS AND METHODS: Continuous wave (CW) non-thermal laser parameters were: 660 nm wavelength, power 15 mW, with a total energy of 0.9 J, fluence of 1.15 J/cm2 , spot size of 0.785 cm2 , and time of 60 seconds. Using in silico analysis, we selected and then, quantified the expression of messenger RNA (mRNA) of 47 genes of 9 signaling pathways associated with MI (angiogenesis, cell survival, hypertrophy, oxidative stress, apoptosis, extracellular matrix, calcium kinetics, cell metabolism, and inflammation). Messenger RNA expression quantification was performed in myocardial samples by polymerase chain reaction real-time array using TaqMan customized plates. RESULTS: Our results evidenced that MI modified mRNA expression of several well-known biomarkers related to detrimental cardiac activity in almost all signaling pathways analyzed. However, PBMT reverted most of these transcriptional changes. More expressively, PBMT provoked a robust decrease in mRNA expression of molecules that participate in post-MI inflammation and ECM composition, such as IL-6, TNF receptor, TGFb1, and collagen I and III. Global microRNA (miRNA) expression analysis revealed that PBMT decreased miR-221, miR-34c, and miR-93 expressions post-MI, which are related to deleterious effects in cardiac remodeling. CONCLUSION: Thus, the identification of transcriptional and post-transcriptional changes induced by PBMT may be used to interfere in the molecular dynamics of cardiac remodeling post-MI.

Low-level laser therapy prevents muscle oxidative stress in rats subjected to high-intensity resistance exercise in a dose-dependent manner.

High-intensity resistance exercise (RE) increases oxidative stress leading to deleterious effects on muscle performance and recovery. The aim of this study was to assess the effect of applying low-level laser therapy (LLLT) prior to a RE session on muscle oxidative stress and to determine the possible influence of the dosimetric parameters. Female Wistar rats were assigned to non-LLLT (Ctr: non-exercised control; RNI: RE) or LLLT groups subjected to RE (radiant energy: 4 J, 8 J, and 12 J, respectively). RE consisted of four maximum load climbs. An 830-nm DMC Lase Photon III was used to irradiate three points in gastrocnemius muscles (two limbs) before exercise. Animals were euthanized after 60 min after the end of the exercise, and muscle tissue was removed for analysis of oxidative stress markers. All doses resulted in the prevention of increased lipoperoxidation; however, LLLT prevented protein oxidation only in rats that were pretreated with 8 J and 12 J of energy by LLLT. RE and LLLT did not change catalase activity. However, RE resulted in lower superoxide dismutase activity, and the opposite was observed in the LLLT group. These data indicate that LLLT prior to RE can prevent muscle oxidative stress. This study is the first to evaluate the impact of dosimetric LLLT parameters on the oxidative stress induced by RE, wherein both 8 J and 12 J of energy afforded significant protection.

Exercise Training Potentiates The Cardioprotective Effects of Stem Cells Post-infarction.

BACKGROUND: Preconditioning of cell recipients may exert a significant role in attenuating the hostility of the infarction milieu, thereby enhancing the efficacy of cell therapy. This study was conducted to examine whether exercise training potentiates the cardioprotective effects of adipose-derived stem cell (ADSC) transplantation following myocardial infarction (MI) in rats. METHODS: Four groups of female Fisher-344 rats were studied: Sham; non-trained rats with MI (sMI); non-trained rats with MI submitted to ADSCs transplantation (sADSC); trained rats with MI submitted to ADSCs (tADSC). Rats were trained 9 weeks prior to MI and ADSCs transplantation. Echocardiography was applied to assess cardiac function. Myocardial performance was evaluated in vitro. Protein expression analyses were carried out by immunoblotting. Periodic acid-Schiff staining was used to analyse capillary density and apoptosis was evaluated with terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay. RESULTS: Echocardiography performed 4 weeks after the infarction revealed attenuated scar size in the both sADSC and tADSC groups compared to the sMI group. However, fractional shortening was improved only in the tADSC group. In vitro myocardial performance was similar between the tADSC and Sham groups. The expression of phosphoSer473Akt1 and VEGF were found to be higher in the hearts of the tADSC group compared to both the sADSC and sMI groups. Histologic analysis demonstrated that tADSC rats had higher capillary density in the remote and border zones of the infarcted sites compared to the sMI rats. CONCLUSIONS: Preconditioning with exercise induces a pro-angiogenic milieu that may potentiate the therapeutic effects of ADSCs on cardiac remodelling following MI.

Predicted Equation for VO2 Based on a 20-Meter Multistage Shuttle Run Test for Children.

This study compared maximum oxygen consumption (VO2max) on a 20-meter multistage shuttle run test (20-Srt) with a cardiopulmonary exercise test (CPET) to determine a VO2max prediction equation for a 20-Srt in children aged 6-10 years. Eighty healthy children performed the CPET on a treadmill, while the 20-Srt took place on a sports court. Heart rate (HR) was measured and the expired gases were continuously measured breath-by-breath using a portable gas analyzer. The VO2max was lower (p<0.05) in CPET than 20-Srt for all, female, and male participants, respectively (46.3±7.9 vs. 48.7±4.6; 42.7±7.8 vs. 46.7±4.8; 49.3±6.8 vs. 50.4±3.9, mL·kg-1·min-1). The standard error estimates were between 3.0 and 3.6 and considered as not clinically relevant if less than 5 mL·kg-1·min-1. The intraclass correlation coefficient between the VO2 in CPET and in 20-Srt was 0.74 (CI95% 0.55-0.84) and considered moderately reliable. The linear multiple regression excluded sex, body mass index and fat-free mass and retained the maximum speed and age in the predictive equation. The 20-Srt estimates the VO2max with moderate reliability and the predictive equation was VO2maxpred=4.302+(maximum speed*5.613)-(age*1.523) for children aged 6-10 years.

Protective effects of photobiomodulation against resistance exercise-induced muscle damage and inflammation in rats.

We investigated whether low-level laser therapy (LLLT) prior to or post resistance exercise could attenuate muscle damage and inflammation. Female Wistar rats were assigned to non-LLLT or LLLT groups. An 830-nm DMC Laser Photon III was used to irradiate their hind legs with 2J, 4J, and 8J doses. Irradiations were performed prior to or post (4J) resistance exercise bouts. Resistance exercise consisted of four maximum load climbs. The load work during a resistance exercise bout was similar between Control (non-LLLT, 225 ± 10 g), 2J (215 ± 8 g), 4J (210 ± 9 g), and 8J (226 ± 9 g) groups. Prior LLLT did not induce climbing performance improvement, but exposure to 4J irradiation resulted in lower blood lactate levels post-exercise. The 4J dose decreased creatine kinase and lactic dehydrogenase levels post-exercise regardless of the time of application. Moreover, 4-J irradiation exposure significantly attenuated tumor necrosis factor alpha, interleukin-6, interleukin-1ß, cytokine-induced neutrophil chemoattractant-1, and monocyte chemoattractant protein-1. There was minor macrophage muscle infiltration in 4J-exposed rats. These data indicate that LLLT prior to or post resistance exercise can reduce muscle damage and inflammation, resulting in muscle recovery improvement. We attempted to determine an ideal LLLT dose for suitable results, wherein 4J irradiation exposure showed a significant protective role.

Dexamethasone-induced cardiac deterioration is associated with both calcium handling abnormalities and calcineurin signaling pathway activation.

Dexamethasone is a potent and widely used anti-inflammatory and immunosuppressive drug. However, recent evidences suggest that dexamethasone cause pathologic cardiac remodeling, which later impairs cardiac function. The mechanism behind the cardiotoxic effect of dexamethasone is elusive. The present study aimed to verify if dexamethasone-induced cardiotoxicity would be associated with changes in the cardiac net balance of calcium handling protein and calcineurin signaling pathway activation. Wistar rats (~400 g) were treated with dexamethasone (35 µg/g) in drinking water for 15 days. After dexamethasone treatment, we analyzed cardiac function, cardiomyocyte diameter, cardiac fibrosis, and the expression of proteins involved in calcium handling and calcineurin signaling pathway. Dexamethasone-treated rats showed several cardiovascular abnormalities, including elevated blood pressure, diastolic dysfunction, cardiac fibrosis, and cardiomyocyte apoptosis. Regarding the expression of proteins involved in calcium handling, dexamethasone increased phosphorylation of phospholamban at threonine 17, reduced protein levels of Na+/Ca2+ exchanger, and had no effect on protein expression of Serca2a. Protein levels of NFAT and GATA-4 were increased in both cytoplasmic and nuclear faction. In addition, dexamethasone increased nuclear protein levels of calcineurin. Altogether our findings suggest that dexamethasone causes pathologic cardiac remodeling and diastolic dysfunction, which is associated with impaired calcium handling and calcineurin signaling pathway activation.

The contributions of dipeptidyl peptidase IV to inflammation in heart failure.

Circulating dipeptidyl peptidase IV (DPPIV) activity correlates with cardiac dysfunction in humans and experimental heart failure (HF) models. Similarly, inflammatory markers are associated with poorer outcomes in HF patients. However, the contributions of DPPIV to inflammation in HF remain elusive. Therefore, this study aimed to investigate whether the cardioprotective effects of DPPIV inhibition after myocardial injury are accompanied by reduced cardiac inflammation, whether circulating DPPIV activity correlates with the levels of systemic inflammatory markers in HF patients, and whether leukocytes and/or splenocytes may be one of the sources of circulating DPPIV in HF. Experimental HF was induced in male Wistar rats by left ventricular myocardial injury after radiofrequency catheter ablation. The rats were divided into three groups: sham, HF, and HF + DPPIV inhibitor (sitagliptin). Six weeks after surgery, cardiac function, perfusion and inflammatory status were evaluated. Sitagliptin treatment improved cardiac function and perfusion, reduced macrophage infiltration, and diminished the levels of inflammatory biomarkers including TNF-α, IL-1ß, and CCL2. In HF patients, serum DPPIV activity correlated with CCL2, suggesting that leukocytes may be the source of circulating DPPIV in HF. Unexpectedly, DPPIV release was higher in splenocytes from HF rats and similar in HF circulating mononuclear cells compared with those from sham, suggesting an organ-specific modulation of DPPIV in HF. Collectively, our data provide new evidence that the cardioprotective effects of DPPIV inhibition in HF may be due to suppression of inflammatory cytokines. Moreover, they suggest that a vicious circle between DPPIV and inflammation may contribute to HF development and progression.

Association of Exercise Training with Tobacco Smoking Prevents Fibrosis but has Adverse Impact on Myocardial Mechanics.

INTRODUCTION: There was no data for cardiac repercussion of exercise training associated with tobacco smoking. This issue is interesting because some smoking people can be enrolled in an exercise-training program. Thus, we evaluated swimming training effects on the function and structural myocardial in rats exposed to tobacco smoking. METHODS: Male Wistar rats were assigned to one of four groups: C, untrained rats without exposure to tobacco smoking; E, exercised rats without exposure to tobacco smoking; CS, untrained rats exposed to tobacco smoking; ECS, exercised rats exposed to tobacco smoking. Rats swam five times a week twice daily (60min per session) for 8 weeks. Before each bout exercise, rats breathed smoke from 20 cigarettes for 60min. Twenty-four hours after the last day of the protocol, papillary muscles were isolated for in vitro analysis of myocardial mechanics. The myocardial mass and nuclear cardiomyocyte volume were used as hypertrophy markers, and collagen content was determined by picrosirius red staining. RESULTS: There was a well-pronounced myocardial hypertrophic effect for two interventions. The exercise blunted myocardial collagen increases induced by tobacco smoking. However, exercise and tobacco-smoking association was deleterious to myocardial performance. Thereby, in vitro experiments with papillary muscles contracting in isometric showed impairment myocardial inotropism in exercised rats exposed to tobacco smoking. CONCLUSIONS: This work presents novel findings on the role of exercise training on cardiac remodeling induced by tobacco smoking. Although exercise has mitigated tissue fibrosis, their association with tobacco smoking exacerbated hypertrophy and in vitro myocardial dysfunction. IMPLICATIONS: This is first study to show that the association of an aerobic exercise training with tobacco smoking intensifies the phenotype of pathological cardiac hypertrophy. Therefore, the combination of interventions resulted in exacerbated myocardial hypertrophy and contractility dysfunction. These findings have significant clinical implication because some smoking people can be enrolled in an exercise-training program.