Novel wasp toxin discriminates between neuronal and cardiac sodium channels

Pompilidotoxins (PMTXs), derived from the venom of solitary wasp has been known to facilitate synaptic transmission in the lobster neuromuscular junction, and a recent further study from rat trigeminal neurons revealed that the toxin slows Na+ channel inactivation without modifying activation process. Here we report that beta -PMTX modifies rat brain type II Na+ channel alpha -subunit (rBII) expressed in human embryonic kidney cells but fails to act on the rat heart alpha -subunit (rH1) at similar concentrations. We constructed a series of chimeric mutants of rBII and rH1 Na+ channels and compared modification of the steady-state Na+ currents by beta -PMTX. We found that a difference in a single amino acid between Glu-1616 in rBII and Gln-1615 in rH1 at the extracellular loop of D4S3-S4 is crucial for the action of beta -PMTX. PMTXs, which are small peptides with 13 amino acids, would be a potential tool for exploring a new functional moiety of Na+ channels.

Myosin heavy chain expression and atrophy in rat skeletal muscle during transition from cardiac hypertrophy to heart failure

The purpose of this investigation was to determine whether changes in myosin heavy chain (MHC) expression and atrophy in rat skeletal muscle are observed during transition from cardiac hypertrophy to chronic heart failure (CHF) induced by aortic stenosis (AS). AS and control animals were studied 12 and 18 weeks after surgery and when overt CHF had developed in AS animals, 28 weeks after the surgery. The following parameters were studied in the soleus muscle: muscle atrophy index (soleus weight/body weight), muscle fibre diameter and frequency and MHC expression. AS animals presented decreases in both MHC1 and type I fibres and increases in both MHC2a and type IIa fibres during late cardiac hypertrophy and CHF. Type IIa fibre atrophy occurred during CHF. In conclusion, our data demonstrate that skeletal muscle phenotype changes occur in both late cardiac hypertrophy and heart failure; this suggests that attention should be given to the fact that skeletal muscle phenotype changes occur prior to overt heart failure symptoms.

Combined effects of age and diet-induced obesity on biochemical parameters and cardiac energy metabolism in rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Efeitos do treinamento físico no IGF-I hepático em ratos diabéticos experimentais

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Influência da atividade das mataloproteinases 2 e 9 na diminuiçao o colágeno tipo I miocárdico em ratos obesos

Pós-graduação em Fisiopatologia em Clínica Médica - FMB

Periostin as a modulator of chronic cardiac remodeling after myocardial infarction

OBJECTIVE: After acute myocardial infarction, during the cardiac repair phase, periostin is released into the infarct and activates signaling pathways that are essential for the reparative process. However, the role of periostin in chronic cardiac remodeling after myocardial infarction remains to be elucidated. Therefore, the objective of this study was to investigate the relationship between tissue periostin and cardiac variables in the chronic cardiac remodeling induced by myocardial infarction. METHODS: Male Wistar rats were assigned to 2 groups: a simulated surgery group (SHAM; n = 8) and a myocardial infarction group (myocardial infarction; n = 13). After 3 months, morphological, functional and biochemical analyses were performed. The data are expressed as means±SD or medians (including the lower and upper quartiles). RESULTS: Myocardial infarctions induced increased left ventricular diastolic and systolic areas associated with a decreased fractional area change and a posterior wall shortening velocity. With regard to the extracellular matrix variables, the myocardial infarction group presented with higher values of periostin and types I and III collagen and higher interstitial collagen volume fractions and myocardial hydroxyproline concentrations. In addition, periostin was positively correlated with type III collagen levels (r = 0.673, p = 0.029) and diastolic (r = 0.678, p = 0.036) and systolic (r = 0.795, p = 0.006) left ventricular areas. Considering the relationship between periostin and the cardiac function variables, periostin was inversely correlated with both the fractional area change (r = -0.783, p = 0.008) and the posterior wall shortening velocity (r = -0.767, p = 0.012). CONCLUSIONS: Periostin might be a modulator of deleterious cardiac remodeling in the chronic phase after myocardial infarction in rats.

Differential effects of variation in athletes training on myocardial morphophysiological adaptation in men: Focus on I-123-MIBG assessed myocardial sympathetic activity

High intensity systematic physical training leads to myocardial morphophysiological adaptations. The goal of this study was to investigate if differences in training were correlated with differences in cardiac sympathetic activity.58 males (19-47 years), were divided into three groups: strength group (SG), (20 bodybuilders), endurance group (EG), (20 endurance athletes), and a control group (CG) comprising 18 healthy non-athletes. Cardiac sympathetic innervation was assessed by planar myocardial I-123-metaiodobenzylguanidine scintigraphy using the early and late heart to mediastinal (H/M) ratio, and washout rate (WR).Left ventricular mass index was significantly higher both in SG (P < .001) and EG (P = .001) compared to CG without a statistical significant difference between SG and EG (P = .417). The relative wall thickness was significantly higher in SG compared to CG (P < .001). Both left ventricular ejection fraction and the peak filling rate showed no significant difference between the groups. Resting heart rate was significantly lower in EG compared to CG (P = .006) and SG (P = .002). The late H/M ratio in CG was significantly higher compared to the late H/M for SG (P = .003) and EG (P = .004). However, WR showed no difference between the groups. There was no significant correlation between the parameters of myocardial sympathetic innervation and parameters of left ventricular function.Strength training resulted in a significant increase in cardiac dimensions. Both strength and endurance training seem to cause a reduction in myocardial sympathetic drive. However, myocardial morphological and functional adaptations to training were not correlated with myocardial sympathetic activity.

Diabetes mellitus activates fetal gene program and intensifies cardiac remodeling and oxidative stress in aged spontaneously hypertensive rats

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Pediatric Perioperative Cardiac Arrest and Mortality: A Study From a Tertiary Teaching Hospital

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Cardiac Energy Metabolism and Oxidative Stress Biomarkers in Diabetic Rat Treated with Resveratrol

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Intraoperative and Anesthesia-Related Cardiac Arrest and Its Mortality in Older Patients: A 15-Year Survey in a Tertiary Teaching Hospital

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Myosin heavy chain expression and atrophy in rat skeletal muscle during transition from cardiac hypertrophy to heart failure

The purpose of this investigation was to determine whether changes in myosin heavy chain (MHC) expression and atrophy in rat skeletal muscle are observed during transition from cardiac hypertrophy to chronic heart failure (CHF) induced by aortic stenosis (AS). AS and control animals were studied 12 and 18 weeks after surgery and when overt CHF had developed in AS animals, 28 weeks after the surgery. The following parameters were studied in the soleus muscle: muscle atrophy index (soleus weight/body weight), muscle fibre diameter and frequency and MHC expression. AS animals presented decreases in both MHC1 and type I fibres and increases in both MHC2a and type IIa fibres during late cardiac hypertrophy and CHF. Type IIa fibre atrophy occurred during CHF. In conclusion, our data demonstrate that skeletal muscle phenotype changes occur in both late cardiac hypertrophy and heart failure; this suggests that attention should be given to the fact that skeletal muscle phenotype changes occur prior to overt heart failure symptoms.

Absence of Interferon-γ–Inducible Gene IGTP Does Not Significantly Alter the Development of Chagasic Cardiomyopathy in Mice Infected with Trypanosoma cruzi (Brazil Strain)

Interferon-γ (IFN-γ) contributes to host resistance during acute infection with Trypanosoma cruzi, the causative agent of Chagas’ disease. Inducibly expressed guanosine triphosphatase (IGTP), a 48-kDa guanosine triphosphatase (GTPase), is a member of a family of GTPase proteins inducibly expressed by IFN-γ. The expression pattern of IGTP suggests that it may mediate IFN-γ–induced responses in a variety of cell types. IGTP has been demonstrated to be important for control of Toxoplasma gondii infection but not for resistance against Listeria monocytogenes. We evaluated the role of IGTP in development of chronic chagasic cardiomyopathy in IGTP null mice and C57X129sv (wild type [WT]) mice infected with the Brazil strain for 6 mo. There was no significant difference in parasitemia or cardiac histopathology between null and WT mice. Right ventricular remodeling was observed in infected IGTP null mice, suggesting that IGTP does not significantly alter the course of T. cruzi infection.

Swimming Training in Rats Increases Cardiac MicroRNA-126 Expression and Angiogenesis

DA SILVA, N. D. JR, T. FERNANDES, U. P. R. SOCI, A. W. A. MONTEIRO, M. I. PHILLIPS, and E. M. DE OLIVEIRA. Swimming Training in Rats Increases Cardiac MicroRNA-126 Expression and Angiogenesis. Med. Sci. Sports Exerc., Vol. 44, No. 8, pp. 1453-1462, 2012. Purpose: MicroRNA (miRNA)-126 is angiogenic and has two validated targets: Sprouty-related protein 1 (Spred-1) and phosphoinositol-3 kinase regulatory subunit 2 (PI3KR2), negative regulators of angiogenesis by VEGF pathway inhibition. We investigated the role of swimming training on cardiac miRNA-126 expression related to angiogenesis. Methods: Female Wistar rats were assigned to three groups: sedentary (S), training 1 (T1, moderate volume), and training 2 (T2, high volume). T1 consisted of 60 min.d(-1) of swimming, five times per week for 10 wk with 5% body overload. T2 consisted of the same protocol of T1 until the eighth week; in the ninth week, rats trained for two times a day, and in the 10th week, rats trained for three times a day. MiRNA and PI3KR2 gene expression analysis was performed by real-time polymerase chain reaction in heart muscle. We assessed markers of training, the cardiac capillary-fiber ratio, cardiac protein expression of VEGF, Spred-1, Raf-1/ERK 1/2, and PI3K/Akt/eNOS. Results: The cardiac capillary-fiber ratio increased in T1 (58%) and T2 (101%) compared with S. VEGF protein expression was increased 42% in T1 and 108% in T2. Cardiac miRNA-126 expression increased 26% (T1) and 42% (T2) compared with S, correlated with angiogenesis. The miRNA-126 target Spred-1 protein level decreased 41% (T1) and 39% (T2), which consequently favored an increase in angiogenic signaling pathway Raf-1/ERK 1/2. On the other hand, the gene expression of PI3KR2, the other miRNA-126 target, was reduced 39% (T1) and 78% (T2), and there was an increase in protein expression of components of the PI3K/Akt/eNOS signaling pathway in the trained groups. Conclusions: This study showed that aerobic training promotes an increase in the expression of miRNA-126 and that this may be related to exercise-induced cardiac angiogenesis, by indirect regulation of the VEGF pathway and direct regulation of its targets that converged in an increase in angiogenic pathways, such as MAPK and PI3K/Akt/eNOS.

SMALL INTERFERING RNA TARGETING FOCAL ADHESION KINASE PREVENTS CARDIAC DYSFUNCTION IN ENDOTOXEMIA

Sepsis and septic shock are associated with cardiac depression. Cardiovascular instability is a major cause of death in patients with sepsis. Focal adhesion kinase (FAK) is a potential mediator of cardiomyocyte responses to oxidative and mechanical stress. Myocardial collagen deposition can affect cardiac compliance and contractility. The aim of the present study was to determine whether the silencing of FAK is protective against endotoxemia-induced alterations of cardiac structure and function. In male Wistar rats, endotoxemia was induced by intraperitoneal injection of lipopolysaccharide (10 mg/kg). Cardiac morphometry and function were studied in vivo by left ventricular catheterization and histology. Intravenous injection of small interfering RNA targeting FAK was used to silence myocardial expression of the kinase. The hearts of lipopolysaccharide-injected rats showed collagen deposition, increased matrix metalloproteinase 2 activity, and myocyte hypertrophy, as well as reduced 24-h +dP/dt and -dP/dt, together with hypotension, increased left ventricular end-diastolic pressure, and elevated levels of FAK (phosphorylated and unphosphorylated). Focal adhesion kinase silencing reduced the expression and activation of the kinase in cardiac tissue, as well as protecting against the increased collagen deposition, greater matrix metalloproteinase 2 activity, and reduced cardiac contractility that occur during endotoxemia. In conclusion, FAK is activated in endotoxemia, playing a role in cardiac remodeling and in the impairment of cardiac function. This kinase represents a potential therapeutic target for the protection of cardiac function in patients with sepsis.