Involvement of L-Type Calcium Channel and SERCA2a in Myocardial Dysfunction Induced by Obesity

Obesity has been shown to impair myocardial performance. Nevertheless, the mechanisms underlying the participation of calcium (Ca2+) handling on cardiac dysfunction in obesity models remain unknown. L-type Ca2+ channels and sarcoplasmic reticulum (SR) Ca2+-ATPase (SERCA2a), may contribute to the cardiac dysfunction induced by obesity. The purpose of this study was to investigate whether myocardial dysfunction in obese rats is related to decreased activity and/or expression of L-type Ca2+ channels and SERCA2a. Male 30-day-old Wistar rats were fed standard (C) and alternately four palatable high-fat diets (Ob) for 15 weeks. Obesity was determined by adiposity index and comorbidities were evaluated. Myocardial function was evaluated in isolated left ventricle papillary muscles under basal conditions and after inotropic and lusitropic maneuvers. L-type Ca2+ channels and SERCA2a activity were determined using specific blockers, while changes in the amount of channels were evaluated by Western blot analysis. Phospholamban (PLB) protein expression and the SERCA2a/PLB ratio were also determined. Compared with C rats, the Ob rats had increased body fat, adiposity index and several comorbidities. The Ob muscles developed similar baseline data, but myocardial responsiveness to post-rest contraction stimulus and increased extracellular Ca2+ was compromised. The diltiazem promoted higher inhibition on developed tension in obese rats. In addition, there were no changes in the L-type Ca2+ channel protein content and SERCA2a behavior (activity and expression). In conclusion, the myocardial dysfunction caused by obesity is related to L-type Ca2+ channel activity impairment without significant changes in SERCA2a expression and function as well as L-type Ca2+ protein levels. J. Cell. Physiol. 226: 2934-2942, 2011. (C) 2011 Wiley-Liss, Inc.

Cerebral ischemia as initial neurological manifestation of atrial myxoma: case report

Infartos cerebrais de etiologia cardíaca são observados em cerca de 20% dos pacientes com acidente vascular cerebral isquêmico. Infarto cerebral ocorre como manifestação clínica inicial em um terço dos casos de mixoma atrial. Embora quase metade dos pacientes com mixoma atrial apresente alteração ao exame neurológico, infarto cerebral não hemorrágico é visto na tomografia computadorizada em praticamente todos os casos. Os autores apresentam o caso de uma paciente, cuja primeira manifestação clínica do mixoma atrial foi um acidente vascular cerebral isquêmico e chamam a atenção para a possibilidade de infarto cerebral silencioso em pacientes portadores de mixoma atrial.

Myocardial contractility of the isovolumetrically beating isolated rat heart

Several indexes of myocardial contractility have been proposed to assess ventricular function in the isovolumetrically beating isolated heart. However, the conclusions reached on the basis of these indexes may be influenced by ventricular geometry rather than contractility itself. The objective of the present study was to assess the performance of widely used contractility indexes in the isovolumetrically beating isolated heart in two experimental models of hypertrophy, the spontaneously hypertensive rat (SHR) and infrarenal aortocava fistula. Compared to normotensive controls (N = 8), SHRs with concentric hypertrophy (N = 10) presented increased maximum rate of ventricular pressure rise (3875 ± 526 vs 2555 ± 359 mmHg/s, P < 0.05) and peak of isovolumetric pressure (187 ± 11 vs 152 ± 11 mmHg, P < 0.05), and decreased developed stress (123 ± 20 vs 152 ± 26 g/cm², P < 0.05) and slope of stress-strain relationship (4.9 ± 0.42 vs 6.6 ± 0.77 g/cm²/%). Compared with controls (N = 11), rats with volume overload-induced eccentric hypertrophy (N = 16) presented increased developed stress (157 ± 38 vs 124 ± 22 g/cm², P < 0.05) and slope of stress-strain relationship (9 ± 2 vs 7 ± 1 g/cm²/%, P < 0.05), and decreased maximum rate of ventricular pressure rise(2746 ± 382 vs 3319 ± 352 mmHg, P < 0.05) and peak of isovolumetric pressure (115 ± 14 vs 165 ± 13 mmHg/s, P < 0.05). The results suggested that indexes of myocardial contractility used in experimental studies may present opposite results in the same heart and may be influenced by ventricular geometry. We concluded that several indexes should be taken into account for proper evaluation of contractile state, in the isovolumetrically beating isolated heart.

Obesity induces upregulation of genes involved in myocardial Ca2+ handling

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

Effect of felodipine on myocardial and renal injury induced by aldosterone-high salt hypertension in uninephrectomized rats

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Influence of educational level on myocardial hypertrophy of hemodialysis patients

Introduction: Chronic renal disease is associated with a high cardiovascular risk. Data from the general population associate cardiovascular diseases with low educational level, but no study has evaluated this association in patients on hemodialysis. Objective: This study aimed at evaluating the association between educational level, hypertension, and left ventricular hypertrophy in patients on chronic hemodialysis. Methods: A standard socioeconomic questionnaire was applied to 79 hemodialysis patients at the Hospital das Clínicas of Faculdade de Medicina de Botucatu, state of São Paulo. Clinical, laboratory and echocardiographic data were obtained from medical records. The patients were divided into two groups according to the median educational level, as follows: G1, patients with three or less years of schooling; G2, patients with more than three years of schooling. Results: Blood pressure, interdialytic weight gain, and variables statistically different in the two groups (p < 0.2) underwent multiple analysis. Independent associations were stated with p < 0.05 in multiple analysis. The mean age of patients was 57 ± 12.8 years, 46 were males (57%), and 53 white (67%). The variables selected for multiple analysis were: age (p = 0.004); educational level (p < 0.0001); body mass index (p = 0.124); left ventricular diameter (p = 0.048); and left ventricular mass index (p = 0.006). Antihypertensive drugs were similar in both groups. Systolic blood pressure (p = 0.006) and years of schooling (p = 0.047) had a significant and independent correlation with left ventricular mass index. Conclusion: In hemodialysis patients, left ventricular mass associated not only with blood pressure but also with educational level.

The effect of 6% Hydroxyethyl starch vs. Ringer's lactate on acute kidney injury after renal ischemia in rats

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

Hypoxic-preconditioning induces neuroprotection against hypoxia-ischemia in newborn piglet brain

Preconditioning-induced ischemic tolerance has been documented in the newborn brain, however, the signaling mechanisms of this preconditioning require further elucidation. The aims of this study were to develop a hypoxic-preconditioning (PC) model of ischemic tolerance in the newborn piglet, which emulates important clinical similarities to human situation of birth asphyxia, and to characterize some of the molecular mechanisms shown to be implicated in PC-induced neuroprotection in rodent models. One day old piglets were subjected to PC (8% O(2)/92% N(2)) for 3 h and 24 h later were exposed to hypoxia-ischemia (HI) produced by a combination of hypoxia (5% FiO(2)) for a period of 30 min and ischemia induced by a period of hypotension (10 min of reduced mean arterial blood pressure; 70% of baseline). Neuropathologic analysis and unbiased stereology, conducted at 24 h, 3 and 7 days of recovery following HI, indicated a substantial reduction in the severity of brain damage in PC piglets compared to non-PC piglets (P<0.05). PC significantly increased the mRNA expression of hypoxia-inducible factor-1 alpha (HIF-1 alpha) and its target gene, vascular endothelial growth factor (VEGF) at 0 h, 6 h, 24 h, 3 and 7 days of recovery. Immunoblot analysis demonstrated that PC resulted in HIF-1 alpha protein stabilization and accumulation in nuclear extracts of cerebral cortex of newborn piglet brain compared to normoxic controls. Protein levels of VEGF increased in a time-dependent manner in both cortex and hippocampus following PC. Double-immunolabeling indicated that VEGF is mainly expressed in neurons, endothelial cells and astroglia. Our study demonstrates for the first time the protective efficacy of PC against hypoxic-ischemic injury in newborn piglet model, which recapitulates many pathophysiological features of asphyxiated human neonates. Furthermore, as has been shown in rodent models of preconditioning, our results suggest that PC-induced protection in neonatal piglets may involve upregulation of VEGF. (C) 2011 Elsevier B.V. All rights reserved.

Comparative study between trimetazidine and ice slush hypothermia in protection against renal ischemia/reperfusion injury in a porcine model

Purpose: The aim of the study was to compare the effects of renal ice slush hypothermia and the use of trimetazidine in the protection against ischemia/reperfusion (I/R) injury.Materials and Methods: Fifteen farm pigs were submitted to left kidney ischemia and right nephrectomy during the same procedure. Animals were divided into three groups. Group 1 was submitted to warm ischemia; Group 2 was submitted to cold ischemia with ice slush; and Group 3 received trimetazidine 20 mg one day and 4 hours before surgery. Ischemia time was 120 minutes in all three groups. Serum creatinine (SCr) and plasma iohexol clearance (CLioh) were measured before surgery and on postoperative days (PODs) 1,3,7, and 14. Semi-quantitative analyses of histological alterations were performed by a pathologist. A p value of < 0.05 was considered significant.Results: All groups showed elevation of serum creatinine in the first week. Serum creatinine was higher in Group 3 in the first and third postoperative days (Mean Cr: 5.5 and 8.1 respectively). Group 2 showed a lower increase in creatinine and a lower decrease in iohexol clearance than the others. Renal function stabilized in the fourteenth POD in all three groups. Analyses of histological alterations did not reach statistical significance between groups.Conclusion: Trimetazidine did not show protection against renal I/R injury in comparison to warm ischemia or hypothermia in a porcine model submitted to 120 minutes of renal ischemia.

Cold Renal Ischemia: Comparison of Efficacy Between Two Techniques of Cooling, in a Swine Model

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

Systemic evaluation on ischemia and reperfusion injury of splanchnic organs in rats

OBJETIVO: Avaliar as alterações hemodinâmicas e sistêmicas decorrentes de isquemia e reperfusão (I/R) esplâncnica em ratos. MÉTODOS: Vinte ratos foram divididos em dois grupos: grupo controle: os animais foram submetidos à cirurgia, mas não a I/R e foram tratados com solução fisiológica (5 ml/kg/h) por 150 minutos; grupo I/R: os animais foram submetidos à administração contínua de solução fisiológica e à oclusão do tronco celíaco, artéria mesentérica superior e artéria mesentérica inferior por 30 minutos, seguidos por 120 minutos de reperfusão. Avaliou-se a pressão arterial média, pressão venosa, fluxo sangüíneo na aorta e na artéria mesentérica superior, freqüência cardíaca, temperatura esofágica e hematócrito. RESULTADOS: Durante a reperfusão, no grupo I/R, houve uma diminuição progressiva da pressão arterial média, fluxo sangüíneo na aorta e artéria mesentérica superior, freqüência cardíaca e temperatura esofágica; pressão venosa e hematócrito não sofreram alteração. CONCLUSÃO: O modelo de isquemia provocado por oclusão da artéria mesentérica superior, artéria mesentérica inferior e tronco celíaco por 30 minutos seguidos por 120 minutos de reperfusão provoca alterações sistêmicas evidenciadas por hipotensão, diminuição do fluxo sangüíneo mesentérico, da freqüência cardíaca e da temperatura esofágica.