Prior exercise training does not prevent acute cardiac alterations after myocardial infarction in female rats

OBJECTIVE: This study aimed to investigate whether previous exercise training could prevent or attenuate acute cardiac alterations after myocardial infarction. METHODS: Female rats were submitted to swim training (1 h/day; 5 days/week) or allowed to remain sedentary for 8 weeks. Afterwards, they were randomly assigned to left coronary artery occlusion or sham surgery. After this procedure, the rats remained sedentary for one week until euthanasia. Cardiac structural and functional analyses were performed using Doppler echocardiography. The rats that had a moderate or large infarct size were included in the evaluations. The data (mean + SEM) were analyzed using a two-way ANOVA model followed byTukey's post-hoc test. RESULTS: After the surgery, no significant difference between the exercise and sedentary groups was observed in the left ventricular infarct sizes (34.58 + 3.04 vs. 37.59 + 3.07). In another group of rats evaluated with Evans blue 1 h after myocardial infarction, no siginificant difference in the area at risk was observed between the exercised and sedentary rats (49.73 + 1.52 vs. 45.48 + 3.49). The changes in the left ventricular fractional areas for the exercised and sedentary myocardial infarction groups (36 + 2% and 39 + 3%, respectively) were smaller than those for the exercise sham surgery (ES, 67+1%) and sedentary sham surgery (SS, 69 + 2%) groups. The E/A was higher in the sedentary myocardial infarction (4.4 + 0.3) and exercised myocardial infarction (5.5 + 0.3) rats than in the SS (2.4 + 0.1) and ES (2.2 + 0.1) rats. CONCLUSION: Previous swim training of female rats does not attenuate systolic and diastolic function alterations after myocardial infarction induced by left coronary artery occlusion, suggesting that cardioprotection cannot be provided by exercise training in this experimental model

Dipeptidyl Peptidase IV Inhibition Exerts Renoprotective Effects in Rats with Established Heart Failure

Circulating dipeptidyl peptidase IV (DPPIV) activity is associated with worse cardiovascular outcomes in humans and experimental heart failure (HF) models, suggesting that DPPIV may play a role in the pathophysiology of this syndrome. Renal dysfunction is one of the key features of HF, but it remains to be determined whether DPPIV inhibitors are capable of improving cardiorenal function after the onset of HF. Therefore, the present study aimed to test the hypothesis that DPPIV inhibition by vildagliptin improves renal water and salt handling and exerts anti-proteinuric effects in rats with established HF. To this end, male Wistar rats were subjected to left ventricle (LV) radiofrequency ablation or sham operation. Six weeks after surgery, radiofrequency-ablated rats who developed HF were randomly divided into two groups and treated for 4 weeks with vildagliptin (120 mg/kg/day) or vehicle by oral gavage. Echocardiography was performed before (pretreatment) and at the end of treatment (post-treatment) to evaluate cardiac function. The fractional area change (FAC) increased (34 +/- 5 vs. 45 +/- 3%, p < 0.05), and the isovolumic relaxation time decreased (33 +/- 2 vs. 27 +/- 1 msp < 0.05) in HF rats treated with vildagliptin (post-treatment vs. pretreatment). On the other hand, cardiac dysfunction deteriorated further in vehicle-treated HF rats. Renal function was impaired in vehicle-treated HF rats as evidenced by fluid retention, low glomerular filtration rate (GFR) and high levels of urinary protein excretion. Vildagliptin treatment restored urinary flow. GFR, urinary sodium and urinary protein excretion to sham levels. Restoration of renal function in HF rats by DPPIV inhibition was associated with increased active glucagon-like peptide-1 (GLP-1) serum concentration, reduced DPPIV activity and increased activity of protein kinase A in the renal cortex. Furthermore, the anti-proteinuric effect of vildagliptin treatment in rats with established HF was associated with upregulation of the apical proximal tubule endocytic receptor megalin and of the podocyte main slit diaphragm proteins nephrin and podocin. Collectively, these findings demonstrate that DPPIV inhibition exerts renoprotective effects and ameliorates cardiorenal function in rats with established HF. Long-term studies with DPPIV inhibitors are needed to ascertain whether these effects ultimately translate into improved clinical outcomes.Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)Univ Sao Paulo, Sch Med, Heart Inst InCor, Sao Paulo, BrazilUniv Fed Sao Paulo, Dept Med, Div Cardiol, Sao Paulo, BrazilUniv Fed Espirito Santo, Dept Physiol Sci, Vitoria, BrazilUniv Fed Sao Paulo, Dept Med, Div Cardiol, Sao Paulo, BrazilFAPESP: 2013/10619-8Web of Scienc

Previous exercise training increases levels of PPAR-α in long-term post-myocardial infarction in rats, which is correlated with better inflammatory response

OBJECTIVE: Exercise is a protective factor for cardiovascular morbidity and mortality, with unclear mechanisms. Changing the myocardial metabolism causes harmful consequences for heart function and exercise contributes to metabolic adjustment modulation. Peroxisome proliferator-activated receptors (PPARs) are also myocardium metabolism regulators capable of decreasing the inflammatory response. We hypothesized that PPAR-α is involved in the beneficial effects of previous exercise on myocardial infarction (MI) and cardiac function, changing the expression of metabolic and inflammatory response regulators and reducing myocardial apoptosis, which partially explains the better outcome. METHODS AND RESULTS: Exercised rats engaged in swimming sessions for 60 min/day, 5 days/week, for 8 weeks. Both the exercised rats and sedentary rats were randomized to MI surgery and followed for 1 week (EI1 or SI1) or 4 weeks (EI4 or SI4) of healing or to sham groups. Echocardiography was employed to detect left ventricular function and the infarct size. Additionally, the TUNEL technique was used to assess apoptosis and immunohistochemistry was used to quantitatively analyze the PPAR-α, TNF-α and NF-κB antigens in the infarcted and non-infarcted myocardium. MI-related mortality was higher in SI4 than in EI4 (25% vs 12%), without a difference in MI size. SI4 exhibited a lower shortening fraction than EI4 did (24% vs 35%) and a higher apoptosis/area rate (3.97±0.61 vs 1.90±1.82) in infarcted areas (both p=0.001). Immunohistochemistry also revealed higher TNF-α levels in SI1 than in EI1 (9.59 vs 4.09,

Low-Level Laser Application in the Early Myocardial Infarction Stage Has No Beneficial Role in Heart Failure

Low-level laser therapy (LLLT) has been targeted as a promising approach that can mitigate post infarction cardiac remodeling. There is some interesting evidence showing that the beneficial role of the LLLT could persist long-term even after the end of the application, but it remains to be systematically evaluated. Therefore, the present study aimed to test the hypothesis that LLLT beneficial effects in the early post-infarction cardiac remodeling could remain in overt heart failure even with the disruption of irradiations. Female Wistar rats were subjected to the coronary occlusion to induce myocardial infarction or Sham operation. A single LLLT application was carried out after 60 s and 3 days post-coronary occlusion, respectively. Echocardiography was performed 3 days and at the end of the experiment (5 weeks) to evaluate cardiac function. After the last echocardiographic examination. LV hemodynamic evaluation was performed at baseline and on sudden afterload increases. Compared with the Sham group, infarcted rats showed increased systolic and diastolic internal diameter as well as a depressed shortening fraction of LV. The only benefit of the LLLT was a higher shortening fraction after 3 days of infarction. However, treated-LLLT rats show a lower shortening fraction in the 5th week of study when compared with Sham and non-irradiated rats. A worsening of cardiac function was confirmed in the hemodynamic analysis as evidenced by the higher LV end-diastolic pressure and lower +dP/dt and dP/dt with five weeks of study. Cardiac functional reserve was also impaired by infarction as evidenced by an attenuated response of stroke work index and cardiac output to a sudden afterload stress, without LLLT repercussions. No significant differences were found in the myocardial expression of Akti NEGF pathway. Collectively, these findings illustrate that LLLT improves LV systolic function in the early post-infarction cardiac remodeling. However, this beneficial effect may be dependent on the maintenance of phototherapy. Long-term studies with LLLT application are needed to establish whether these effects ultimately translate into improved cardiac remodeling.Conselho Nacional de Desenvolvimento Cientifico e TecnologicoFAPESPNove de Julho Univ, Lab Biophoton, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Lab Cardiac Physiol, Sao Paulo, SP, BrazilNove de Julho Univ, Program Med, Sao Paulo, BrazilUniv Sao Judas Tadeu, Brazil Phys Educ & Aging Sci Program, Translat Physiol Lab, Sao Paulo, BrazilUniv Fed Sao Paulo, Lab Cardiac Physiol, Sao Paulo, SP, BrazilCNPq: 4400851/2014-8FAPESP: 09-54225/8FAPESP: 15/11028-9Web of Scienc

Rat Adipose Tissue-Derived Stem Cells Transplantation Attenuates Cardiac Dysfunction Post Infarction and Biopolymers Enhance Cell Retention

Background: Cardiac cell transplantation is compromised by low cell retention and poor graft viability. Here, the effects of co-injecting adipose tissue-derived stem cells (ASCs) with biopolymers on cell cardiac retention, ventricular morphometry and performance were evaluated in a rat model of myocardial infarction (MI). Methodology/Principal Findings: (99m)Tc-labeled ASCs (1 x 10(6) cells) isolated from isogenic Lewis rats were injected 24 hours post-MI using fibrin a, collagen (ASC/C), or culture medium (ASC/M) as vehicle, and cell body distribution was assessed 24 hours later by gamma-emission counting of harvested organs. ASC/F and ASC/C groups retained significantly more cells in the myocardium than ASC/M (13.8+/-2.0 and 26.8+/-2.4% vs. 4.8+/-0.7%, respectively). Then, morphometric and direct cardiac functional parameters were evaluated 4 weeks post-MI cell injection. Left ventricle (LV) perimeter and percentage of interstitial collagen in the spare myocardium were significantly attenuated in all ASC-treated groups compared to the non-treated (NT) and control groups (culture medium, fibrin, or collagen alone). Direct hemodynamic assessment under pharmacological stress showed that stroke volume (SV) and left ventricle end-diastolic pressure were preserved in ASC-treated groups regardless of the vehicle used to deliver ASCs. Stroke work (SW), a global index of cardiac function, improved in ASC/M while it normalized when biopolymers were co-injected with ASCs. A positive correlation was observed between cardiac ASCs retention and preservation of SV and improvement in SW post-MI under hemodynamic stress. Conclusions: We provided direct evidence that intramyocardial injection of ASCs mitigates the negative cardiac remodeling and preserves ventricular function post-MI in rats and these beneficial effects can be further enhanced by administrating co-injection of ASCs with biopolymers.Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)[01/0009-0]Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)[05/54695-3]Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)[04/06784-4]Ministerio da Ciencia e Tecnologia/Conselho Nacional de Desenvolvimento Cientifico e Tecnologico/Ministerio da Saude/Departamento Ciencia e Tecnologia (MCT/CNPq/MS/DECIT)[552324/20005-1]Ministerio da Ciencia e Tecnologia/Conselho Nacional de Desenvolvimento Cientifico e Tecnologico/Ministerio da Saude/Departamento Ciencia e Tecnologia (MCT/CNPq/MS/DECIT)[10120104096700]CNPq[141276/2004-5

Use of afterload hemodynamic stress as a practical method for assessing cardiac performance in rats with heart failure

After myocardial infarction, the hemodynamics under basal conditions might appear to be unaltered, which makes it difficult to identify cardiac dysfunction by the usual approaches. Thus, we tested the response to sudden afterload stress in infarcted rats with apparently normal ejection function. Control (CT) and infarcted (MI) Wistar rats with various MI sizes were submitted to echocardiography 30 days after coronary occlusion, followed by assessment of hemodynamics under basal conditions and during a pharmacologically induced sudden pressure overload (phenylephrine 15-25 mg/kg, i.v.). Coronary occlusion resulted in cardiac remodeling proportional to MI size, although several functional parameters such as systolic pressure (SP), stroke volume (SV), and stroke work (SW) of all MI rats were similar to those of CT rats. However, the afterload stress that was produced led to a relative preservation of SV and an increase of SW in CT rats; MI rats exhibited a significant reduction in SV and SW generation, although global cardiac function was normal under basal conditions, as indicated by regular echocardiography and hemodynamics assessment. Thus, we propose the use of sudden pharmacologically induced afterload stress as a practical and efficient procedure for identifying impaired performance of the heart in anesthetized rats, providing an additional physiological variable to be evaluated in experimental therapeutic studies.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Universidade Federal de São Paulo, Div Cardiol, São Paulo, BrazilUniversidade Federal de São Paulo, Cardioresp Physiol Div, São Paulo, BrazilUniversidade Federal de São Paulo, Div Cardiol, São Paulo, BrazilUniversidade Federal de São Paulo, Cardioresp Physiol Div, São Paulo, BrazilWeb of Scienc