Avaliação de cardiotoxicidade subclínica tardia em pacientes com diagnóstico prévio de linfoma não Hodgkin tratados com antraciclinas

Pós-graduação em Fisiopatologia em Clínica Médica - FMB

Aspectos estruturais e moleculares do músculo cardíaco durante a transição entre a disfunção e a insuficiência cardiaca

Pós-graduação em Biologia Geral e Aplicada - IBB

Avaliação de cardiotoxicidade subclínica tardia em pacientes com diagnóstico prévio de linfoma não Hodgkin tratados com antraciclinas

Pós-graduação em Fisiopatologia em Clínica Médica - FMB

Aspectos estruturais e moleculares do músculo cardíaco durante a transição entre a disfunção e a insuficiência cardiaca

Pós-graduação em Biologia Geral e Aplicada - IBB

Exercise training prevents diastolic dysfunction induced by metabolic syndrome in rats

OBJECTIVE: High fructose consumption contributes to the incidence of metabolic syndrome and, consequently, to cardiovascular outcomes. We investigated whether exercise training prevents high fructose diet-induced metabolic and cardiac morphofunctional alterations. METHODS: Wistar rats receiving fructose overload (F) in drinking water (100 g/l) were concomitantly trained on a treadmill (FT) for 10 weeks or kept sedentary. These rats were compared with a control group (C). Obesity was evaluated by the Lee index, and glycemia and insulin tolerance tests constituted the metabolic evaluation. Blood pressure was measured directly (Windaq, 2 kHz), and echocardiography was performed to determine left ventricular morphology and function. Statistical significance was determined by one-way ANOVA, with significance set at p<0.05. RESULTS: Fructose overload induced a metabolic syndrome state, as confirmed by insulin resistance (F: 3.6 +/- 0.2 vs. C: 4.5 +/- 0.2 mg/dl/min), hypertension (mean blood pressure, F: 118 +/- 3 vs. C: 104 +/- 4 mmHg) and obesity (F: 0.31 +/- 0.001 vs. C: 0.29 +/- 0.001 g/mm). Interestingly, fructose overload rats also exhibited diastolic dysfunction. Exercise training performed during the period of high fructose intake eliminated all of these derangements. The improvements in metabolic parameters were correlated with the maintenance of diastolic function. CONCLUSION: The role of exercise training in the prevention of metabolic and hemodynamic parameter alterations is of great importance in decreasing the cardiac morbidity and mortality related to metabolic syndrome.

Lovastatin protects mithochondrial and renal function in kidney ischemia-reperfusion in rats

PURPOSE: To investigate the effect of lovastatin on renal ischemia followed by reperfusion. METHODS: Thirty one Wistar rats submitted to left renal ischemia for 60 minutes followed by contralateral nephrectomy were divided into two groups: A (n = 17, control, no treatment), and B (n = 14, lovastatin 15 mg/kg/day p.o. ten days before ischemia). The animals were sacrificed at the end of ischemia, after 24 hours and at seven days after reperfusion. Survival, serum urea and creatinine levels and renal mitochondrial function were evaluated. RESULTS: Mortality was 29.4% in group A and 0.7% in group B. Urea and creatinine levels were increased in both groups, but the values were significantly lower in group B. Mitochondrial function showed decoupling in 83.4% of group A, as opposed to 38.4/% of group B. CONCLUSIONS: The result shows a protective action of renal function by lovastatin administered before ischemia/reperfusion. Since most of the mitochondrial fraction presented membranes with the ability to maintain ATP production in group B, stabilization of the mitochondrial membrane should be considered as part of the protective action of lovastatin on renal function in ischemia/reperfusion.

Pilates in Heart Failure Patients: A Randomized Controlled Pilot Trial

Background: Conventional cardiac rehabilitation program consist of 15 min of warm-up, 30 min of aerobic exercise and followed by 15 min calisthenics exercise. The Pilates method has been increasingly applied for its therapeutic benefits, however little scientific evidence supports or rebukes its use as a treatment in patients with heart failure (HF). Purpose: Investigate the effects of Pilates on exercise capacity variables in HF. Methods: Sixteen pts with HF, left ventricular ejection fraction 27 +/- 14%, NYHA class III were randomly assigned to conventional cardiac rehabilitation program (n = 8) or mat Pilates training (n = 8) for 16 weeks of 30 min of aerobic exercise followed by 20 min of the specific program. Results: At 16 weeks, pts in the mat Pilates group and conventional group showed significantly increase on exercise time 11.9 +/- 2.5 to 17.8 +/- 4 and 11.7 +/- 3.9 to 14.2 +/- 4 min, respectively. However, only the Pilates group increased significantly the ventilation (from 56 +/- 20 to 69 +/- 17 L/min, P= 0.02), peak VO2 (from 20.9 +/- 6 to 24.8 +/- 6 mL/kg/min, P= 0.01), and O-2 pulse (from 11.9 +/- 2 to 13.8 +/- 3 mL/bpm, P= 0.003). The Pilates group showed significantly increase in peak VO2 when compared with conventional group (24.8 +/- 6 vs. 18.3 +/- 4, P= 0.02). Conclusions: The result suggests that the Pilates method may be a beneficial adjunctive treatment that enhances functional capacity in patients with HF who are already receiving standard medical therapy.

Pulmonary root translocation in malposition of great arteries repair allows right ventricular outflow tract growth

Objective: Optimal surgical treatment of patients with transposition of the great arteries (TGA), ventricular septal defect (VSD), and pulmonary stenosis (PS) remains a matter of debate. This study evaluated the clinical outcome and right ventricle outflow tract performance in the long-term follow-up of patients subjected to pulmonary root translocation (PRT) as part of their surgical repair. Methods: From April 1994 to December 2010, we operated on 44 consecutive patients (median age, 11 months). All had malposition of the great arteries as follows: TGA with VSD and PS (n = 33); double-outlet right ventricle with subpulmonary VSD (n = 7); double-outlet right ventricle with atrioventricular septal defect (n = 1); and congenitally corrected TGA with VSD and PS (n 3). The surgical technique consisted of PRT from the left ventricle to the right ventricle after construction of an intraventricular tunnel that diverted blood flow from the left ventricle to the aorta. Results: The mean follow-up time was 72 +/- 52.1 months. There were 3 (6.8%) early deaths and 1 (2.3%) late death. Kaplan-Meier survival was 92.8% and reintervention-free survival was 82.9% at 12 years. Repeat echocardiographic data showed nonlinear growth of the pulmonary root and good performance of the valve at 10 years. Only 4 patients required reinterventions owing to right ventricular outflow tract problems. Conclusions: PRT is a good surgical alternative for treatment of patients with TGA complexes, VSD, and PS, with acceptable operative risk, high long-term survivals, and few reinterventions. Most patients had adequate pulmonary root growth and performance. (J Thorac Cardiovasc Surg 2012;143:1292-8)

Left cardiac sympathetic denervation for treatment of symptomatic systolic heart failure patients: a pilot study

To evaluate the feasibility, safety, and potential beneficial effects of left cardiac sympathetic denervation (LCSD) in systolic heart failure (HF) patients. In this prospective, randomized pilot study, inclusion criteria were New York Heart Association (NYHA) functional class II or III, left ventricular ejection fraction (LVEF) 40, sinus rhythm, and resting heart rate 65 b.p.m., despite optimal medical therapy (MT). Fifteen patients were randomly assigned either to MT alone or MT plus LCSD. The primary endpoint was safety, measured by mortality in the first month of follow-up and morbidity according to pre-specified criteria. Secondary endpoints were exercise capacity, quality of life, LVEF, muscle sympathetic nerve activity (MSNA), brain natriuretic peptide (BNP) levels and 24 h Holter mean heart rate before and after 6 months. We studied clinical effects in long-term follow-up. Ten patients underwent LCSD. There were no adverse events attributable to surgery. In the LCSD group, LVEF improved from 25 6.6 to 33 5.2 (P 0.03); 6 min walking distance improved from 167 35 to 198 47 m (P 0.02). Minnesota Living with Heart Failure Questionnaire (MLWHFQ) score physical dimension changed from 21 5 to 15 7 (P 0.06). The remaining analysed variables were unchanged. During 848 549 days of follow-up, in the MT group, three patients either died or underwent cardiac transplantation (CT), while in the LCSD group six were alive without CT. LCSD was feasible and seemed to be safe in systolic HF patients. Its beneficial effects warrant the development of a larger randomized trial. Trail registration: NCT01224899.

Initial experience with Pomerantzeff's technique for reduction of the size of giant left atrium

Introduction: The most common indication for surgical correction of giant left atrium is associated with mitral valve insufficiency with or without atrial fibrillation. Several techniques for this purpose are already described with varying results. Objective: To present the initial experience with the tangential triangular resection technique (Pomerantzeff). Methods: From 2002 to 2010, four patients underwent mitral valve operation with reduction of left atrial volume by the technique of triangular resection tangential in our service. Three patients were female. The age ranged from 21 to 51 years old. The four patients presented with atrial fibrillation. Ejection fraction of left ventricle preoperatively ranged from 38% to 62%. The left atrial diameter ranged from 78mm to 140mm. After treatment of mitral dysfunction, the left atrium was reduced by resecting triangular tangential posterior wall between the pulmonary veins to avoid anatomic distortion of the mitral valve or pulmonary veins, reducing tension in the suture line. Results: Average hospital stay was 21.5 +/- 6.5 days. The mean cardiopulmonary bypass time was 130 +/- 30 minutes. There was no surgical bleeding or mortality in the postoperative period. All patients had sinus rhythm restored in the output of cardiopulmonary bypass, maintaining this rate postoperatively. The average diameter of the left atrium was reduced by 50.5% +/- 19.5%. The left ventricular ejection fraction improved in all patients. Conclusion: Initial results with this technique have shown effective reduction of the left atrium.

Increased NHE3 abundance and transport activity in renal proximal tubule of rats with heart failure

Inoue BH, dos Santos L, Pessoa TD, Antonio EL, Pacheco BPM, Savignano FA, Carraro-Lacroix LR, Tucci PJF, Malnic G, Girardi ACC. Increased NHE3 abundance and transport activity in renal proximal tubule of rats with heart failure. Am J Physiol Regul Integr Comp Physiol 302: R166-R174, 2012. First published October 26, 2011; doi:10.1152/ajpregu.00127.2011.-Heart failure (HF) is associated with a reduced effective circulating volume that drives sodium and water retention and extracellular volume expansion. We therefore hypothesized that Na(+)/H(+) exchanger isoform 3 (NHE3), the major apical transcellular pathway for sodium reabsorption in the proximal tubule, is upregulated in an experimental model of HF. HF was induced in male rats by left ventricle radiofrequency ablation. Sham-operated rats (sham) were used as controls. At 6 wk after surgery, HF rats exhibited cardiac dysfunction with a dramatic increase in left ventricular end-diastolic pressure. By means of stationary in vivo microperfusion and pH-dependent sodium uptake, we demonstrated that NHE3 transport activity was significantly higher in the proximal tubule of HF compared with sham rats. Increased NHE3 activity was paralleled by increased renal cortical NHE3 expression at both protein and mRNA levels. In addition, the baseline PKA-dependent NHE3 phosphorylation at serine 552 was reduced in renal cortical membranes of rats with HF. Collectively, these results suggest that NHE3 is upregulated in the proximal tubule of HF rats by transcriptional, translational, and posttranslational mechanisms. Enhanced NHE3-mediated sodium reabsorption in the proximal tubule may contribute to extracellular volume expansion and edema, the hallmark feature of HF. Moreover, our study emphasizes the importance of undertaking a cardiorenal approach to contain progression of cardiac disease.

Induction of Psychosis by Delta 9-Tetrahydrocannabinol Reflects Modulation of Prefrontal and Striatal Function During Attentional Salience Processing

Context: The aberrant processing of salience is thought to be a fundamental factor underlying psychosis. Cannabis can induce acute psychotic symptoms, and its chronic use may increase the risk of schizophrenia. We investigated whether its psychotic effects are mediated through an influence on attentional salience processing. Objective: To examine the effects of Delta 9-tetrahydrocannabinol (Delta 9-THC) and cannabidiol (CBD) on regional brain function during salience processing. Design: Volunteers were studied using event-related functional magnetic resonance imaging on 3 occasions after administration of Delta 9-THC, CBD, or placebo while performing a visual oddball detection paradigm that involved allocation of attention to infrequent (oddball) stimuli within a string of frequent (standard) stimuli. Setting: University center. Participants: Fifteen healthy men with minimal previous cannabis use. Main Outcome Measures: Symptom ratings, task performance, and regional brain activation. Results: During the processing of oddball stimuli, relative to placebo, Delta 9-THC attenuated activation in the right caudate but augmented it in the right prefrontal cortex. Delta 9-Tetrahydrocannabinol also reduced the response latency to standard relative to oddball stimuli. The effect of Delta 9-THC in the right caudate was negatively correlated with the severity of the psychotic symptoms it induced and its effect on response latency. The effects of CBD on task-related activation were in the opposite direction of those of Delta 9-THC; relative to placebo, CBD augmented left caudate and hippocampal activation but attenuated right prefrontal activation. Conclusions: Delta 9-Tetrahydrocannabinol and CBD differentially modulate prefrontal, striatal, and hippocampal function during attentional salience processing. These effects may contribute to the effects of cannabis on psychotic symptoms and on the risk of psychotic disorders.

Regular and moderate exercise before experimental sepsis reduces the risk of lung and distal organ injury

de Araujo CC, Silva JD, Samary CS, Guimaraes IH, Marques PS, Oliveira GP, do Carmo LGRR, Goldenberg RC, Bakker-Abreu I, Diaz BL, Rocha NN, Capelozzi VL, Pelosi P, Rocco PRM. Regular and moderate exercise before experimental sepsis reduces the risk of lung and distal organ injury. J Appl Physiol 112: 1206-1214, 2012. First published January 19, 2012; doi:10.1152/japplphysiol.01061.2011.-Physical activity modulates inflammation and immune response in both normal and pathologic conditions. We investigated whether regular and moderate exercise before the induction of experimental sepsis reduces the risk of lung and distal organ injury and survival. One hundred twenty-four BALB/c mice were randomly assigned to two groups: sedentary (S) and trained (T). Animals in T group ran on a motorized treadmill, at moderate intensity, 5% grade, 30 min/day, 3 times a week for 8 wk. Cardiac adaptation to exercise was evaluated using echocardiography. Systolic volume and left ventricular mass were increased in T compared with S group. Both T and S groups were further randomized either to sepsis induced by cecal ligation and puncture surgery (CLP) or sham operation (control). After 24 h, lung mechanics and histology, the degree of cell apoptosis in lung, heart, kidney, liver, and small intestine villi, and interleukin (IL)-6, KC (IL-8 murine functional homolog), IL-1 beta, IL-10, and number of cells in bronchoalveolar lavage (BALF) and peritoneal lavage (PLF) fluids as well as plasma were measured. In CLP, T compared with S groups showed: 1) improvement in survival; 2) reduced lung static elastance, alveolar collapse, collagen and elastic fiber content, number of neutrophils in BALF, PLF, and plasma, as well as lung and distal organ cell apoptosis; and 3) increased IL-10 in BALF and plasma, with reduced IL-6, KC, and IL-1 beta in PLF. In conclusion, regular and moderate exercise before the induction of sepsis reduced the risk of lung and distal organ damage, thus increasing survival.

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.

Sildenafil vs. Sodium Nitroprusside for the Pulmonary Hypertension Reversibility Test Before Cardiac Transplantation

Background: Pulmonary hypertension is associated with a worse prognosis after cardiac transplantation. The pulmonary hypertension reversibility test with sodium nitroprusside (SNP) is associated with a high rate of systemic arterial hypotension, ventricular dysfunction of the transplanted graft and high rates of disqualification from transplantation. Objective: This study was aimed at comparing the effects of sildenafil (SIL) and SNP on hemodynamic, neurohormonal and echocardiographic variables during the pulmonary reversibility test. Methods: The patients underwent simultaneously right cardiac catheterization, echocardiography, BNP measurement, and venous blood gas analysis before and after receiving either SNP (1 - 2 mu g/kg/min) or SIL (100 mg, single dose). Results: Both drugs reduced pulmonary hypertension, but SNP caused a significant systemic hypotension (mean blood pressure - MBP: 85.2 vs. 69.8 mm Hg; p < 0.001). Both drugs reduced cardiac dimensions and improved left cardiac function (SNP: 23.5 vs. 24.8%, p = 0.02; SIL: 23.8 vs. 26%, p < 0.001) and right cardiac function (SIL: 6.57 +/- 2.08 vs. 8.11 +/- 1.81 cm/s, p = 0.002; SNP: 6.64 +/- 1.51 vs. 7.72 +/- 1.44 cm/s, p = 0.003), measured through left ventricular ejection fraction and tissue Doppler, respectively. Sildenafil, contrary to SNP, improved venous oxygen saturation, measured on venous blood gas analysis. Conclusion: Sildenafil and SNP are vasodilators that significantly reduce pulmonary hypertension and cardiac geometry, in addition to improving biventricular function. Sodium nitroprusside, contrary to SIL, was associated with systemic arterial hypotension and worsening of venous oxygen saturation. (Arq Bras Cardiol 2012;99(3):848-856)