Direct effects of colchicine on myocardial function - Studies in hypertrophied and failing spontaneously hypertensive rats

The aging spontaneously hypertensive rat (SHR) is a model in which the transition from chronic stable left ventricular hypertrophy to overt heart failure can be observed. Although the mechanisms for impaired function in hypertrophied and failing cardiac muscle from the SHR have been studied, none accounts fully for the myocardial contractile abnormalities. The cardiac cytoskeleton has been implicated as a possible cause for myocardial dysfunction. If an increase in microtubules contributes to dysfunction, then myocardial microtubule disruption by colchicine should promote an improvement in cardiac performance. We studied the active and passive properties of isolated left ventricular papillary muscles from 18- to 24-month-old SHR with evidence of heart failure (SHR-F, n=6), age-matched SHR without heart failure (SHR-NF, n=6), and age-matched normotensive Wistar-Kyoto rats (WKY, n=5). Mechanical parameters were analyzed before and up to 90 minutes after the addition of colchicine (10(-5), 10(-4), and 10(-3) mol/L). In the baseline state, active tension (AT) developed by papillary muscles from the WKY group was greater than for SHR-NF and SHR-F groups (WKY 5.69+/-1.47 g/mm(2) [mean+/-SD], SHR-NF 3.41+/-1.05, SHR-F 2.87+/-0.26; SHR-NF and SHR-F P<0.05 versus WKY rats). The passive stiffness was greater in SHR-F than in the WKY and SHR-NF groups (central segment exponential stiffness constant, K-cs: SHR-F 70+/-25, SHR-NF 44+/-17, WKY 41+/-13 [mean+/-SD]; SHR-F P<0.05 versus; SHR-NF and WKY rats). AT did not improve after 10, 20, and 30 minutes of exposure to colchicine (10(-5), 10(-4), and 10(-3) mol/L) in any group. In the SHR-F group, AT and passive stiffness did not change after 30 to 90 minutes of colchicine exposure (10(-4) mol/L). In summary, the data in this study fail to demonstrate improvement of intrinsic muscle function in SHR with heart failure after colchicine. Thus, in the SHR there is no evidence that colchicine-induced cardiac microtubular depolymerization affects the active or passive properties of hypertrophied or failing left ventricular myocardium.

Effects of protein-calorie restriction on mechanical function of hypertrophied cardiac muscle

OBJECTIVE: To assess the effect of food restriction (FR) on hypertrophied cardiac muscle in spontaneously hypertensive rats (SHR). METHODS: Isolated papillary muscle preparations of the left ventricle (LV) of 60-day-old SHR and of normotensive Wistar-Kyoto (WKY) rats were studied. The rats were fed either an unrestricted diet or FR diet (50% of the intake of the control diet) for 30 days. The mechanical function of the muscles was evaluated through monitoring isometric and isotonic contractions. RESULTS: FR caused: 1) reduction in the body weight and LV weight of SHR and WKY rats; 2) increase in the time to peak shortening and the time to peak developed tension (DT) in the hypertrophied myocardium of the SHR; 3) diverging changes in the mechanical function of the normal cardiac muscles of WKY rats with reduction in maximum velocity of isotonic shortening and of the time for DT to decrease 50% of its maximum value, and increase of the resting tension and of the rate of tension decline. CONCLUSION: Short-term FR causes prolongation of the contraction time of hypertrophied muscles and paradoxal changes in mechanical performance of normal cardiac fibers, with worsening of the shortening indices and of the resting tension, and improvement of the isometric relaxation.

Insuficiência cardíaca com fração de ejeção normal

A insuficiência cardíaca com fração de ejeção normal (ICFEN) é uma síndrome complexa que vem sendo largamente estudada, desde a última década. É causada por disfunção ventricular diastólica evidenciada por métodos complementares, como estudo hemodinâmico ou ecocardiograma, na presença de fração de ejeção preservada. Acomete preferencialmente indivíduos mais idosos e com comorbidades, como hipertensão arterial sistêmica, insuficiência coronariana e obesidade. Os mecanismos fisiopatológicos são complexos e multifatoriais, envolvendo a rigidez passiva do miocárdio, a geometria ventricular, a força de contenção do pericárdio e a interação entre os ventrículos. Os objetivos principais do tratamento são reduzir a congestão venosa pulmonar, a frequência cardíaca e controlar as comorbidades. Ainda não há evidências fortes de que o uso de medicações específicas, como inibidores de enzima de conversão ou betabloqueadores, interfiram na mortalidade. Os fatores de pior prognóstico incluem a idade avançada, presença de disfunção renal, diabete, classe funcional III e IV (NYHA) e estágio avançado de disfunção diastólica, com padrão restritivo ao enchimento ventricular. Outro aspecto que vem ganhando espaço na literatura é o questionamento do papel da disfunção sistólica nos quadros de ICFEN. Todos esses aspectos são abordados detalhadamente na presente revisão.

Early initiation of dialysis: mortality and renal function recovery in acute kidney injury patients

INTRODUÇÃO: A decisão de quando iniciar a diálise em pacientes com lesão renal aguda (LRA) que apresentam síndrome urêmica está bem estabelecida, entretanto, com ureia < 200 mg/dl o melhor momento para iniciar a diálise torna-se incerto. OBJETIVO: Este estudo teve como objetivo avaliar a mortalidade e a recuperação da função renal em pacientes com LRA, cujo início da diálise ocorreu em diferentes níveis de ureia. MÉTODOS: Estudo retrospectivo desenvolvido em hospital escola, no estado de São Paulo, Brasil, envolvendo 86 pacientes submetidos à diálise. RESULTADOS: A diálise foi iniciada com uréia > 150 mg/dl em 23 pacientes (grupo I) e uréia > 150 mg/dl em 63 pacientes (grupo II). Hipervolemia e mortalidade foram mais frequentes no grupo I que no grupo II (65,2 x 14,2% - p < 0,05; 39,1 x 68,9% - p < 0,05, respectivamente). Entre os sobreviventes, a recuperação renal foi maior no grupo I (71,4 e 36,8%, respectivamente, p < 0,05). A análise multivariada mostrou risco independente de mortalidade relacionado à sepse, idade > 60 anos, diálise peritoneal e uréia > 150 mg/dl no início da diálise. CONCLUSÃO: Menor mortalidade e maior recuperação renal estão associadas com o diálise iniciada precocemente, conforme baixos níveis de ureia, em pacientes com LRA.

Prevalence and predictors of ventricular remodeling after anterior myocardial infarction in the era of modern medical therapy

Background: The consequences of aggressive therapy following a myocardial infarction (MI) on ventricular remodeling are not well established. Thus, the objective of this study was to analyze the prevalence, clinical characteristics, and predictors of left ventricular remodeling in the era of modern medical therapy.Material/Methods: Clinical characteristics and echocardiographic data were analyzed in 66 consecutive patients with anterior infarction at admission and at 6-month follow-up. Ventricular remodeling was defined as an increase of 10% in ventricular end-systolic or end-diastolic diameter.Results: In our study, 58% of patients presented with ventricular remodeling. Patients with remodeling possessed higher total plasma creatine kinase (CPK), MB-fraction (CPK-MB), heart rate, heart failure, shortness of breath, and reperfusion therapy than patients without remodeling. In contrast, patients with remodeling had a smaller ejection fraction, E-Wave deceleration time (EDT), and early (E' Wave) and late (A' Wave) diastolic mitral annulus velocity (average of septal and lateral walls), but a higher E/E' than patients without remodeling. Patients with remodeling used more diuretics, digoxin, oral anticoagulants and aldosterone antagonists than patients without remodeling. In the multivariate analyses, only E' Wave was an independent predictor of ventricular remodeling. Each 1 unit increase in the E' Wave was associated with a 59% increased odds of ventricular remodeling.Conclusions: In patients with anterior MI, despite contemporary treatment, ventricular remodeling is still a common event. In addition, diastolic function can have an important role as a predictor of remodeling in this scenario.

Continuous peritoneal dialysis compared with daily hemodialysis in patients with acute kidney injury

Background: In some parts of the world, peritoneal dialysis is widely used for renal replacement therapy (RRT) in acute kidney injury (AKI), despite concerns about its inadequacy. It has been replaced in recent years by hemodialysis and, most recently, by continuous venovenous therapies. We performed a prospective study to determine the effect of continuous peritoneal dialysis (CPD), as compared with daily hemodialysis (dHD), on survival among patients with AKI.Methods: A total of 120 patients with acute tubular necrosis (ATN) were assigned to receive CPD or dHD in a tertiary-care university hospital. The primary endpoint was hospital survival rate; renal function recovery and metabolic, acid-base, and fluid controls were secondary endpoints.Results: of the 120 patients, 60 were treated with CPD (G1) and 60 with dHD (G2). The two groups were similar at the start of RRT with respect to age (64.2 +/- 19.8 years vs 62.5 +/- 21.2 years), sex (men: 72% vs 66%), sepsis (42% vs 47%), shock (61% vs 63%), severity of AKI [Acute Tubular Necrosis Individual Severity Score (ATNISS): 0.68 +/- 0.2 vs 0.66 +/- 0.22; Acute Physiology and Chronic Health Evaluation (APACHE) II: 26.9 +/- 8.9 vs 24.1 +/- 8.2], pre-dialysis blood urea nitrogen [BUN (116.4 +/- 33.6 mg/dL vs 112.6 +/- 36.8 mg/dL)], and creatinine (5.85 +/- 1.9 mg/dL vs 5.95 +/- 1.4 mg/dL). In G1, weekly delivered Kt/V was 3.59 +/- 0.61, and in G2, it was 4.76 +/- 0.65 (p < 0.01). The two groups were similar in metabolic and acid-base control (after 4 sessions, BUN < 55 mg/dL: 46 +/- 18.7 mg/dL vs 52 +/- 18.2 mg/dL; pH: 7.41 vs 7.38; bicarbonate: 22.8 +/- 8.9 mEq/L vs 22.2 +/- 7.1 mEq/L). Duration of therapy was longer in G2 (5.5 days vs 7.5 days; p = 0.02). Despite the delivery of different dialysis methods and doses, the survival rate did not differ between the groups (58% in G1 vs 52% in G2), and recovery of renal function was similar (28% vs 26%).Conclusion: High doses of CPD provided appropriate metabolic and pH control, with a rate of survival and recovery of renal function similar to that seen with dHD. Therefore, CPD can be considered an alternative to other forms of RRT in AKI.

A function to predict the risk for death in the neonatal sepsis

This was a prospective study of 43 septic neonates at the NICU of the School of Medicine of Botucatu, São Paulo State University. Clinical and laboratory data of sepsis were analyzed based on outcome divided into two groups, survival and death. We calculated the discriminatory power of the relevant variables for the diagnosis of sepsis in each group, and using software for Discriminant Analysis, a function was proposed. There were 43 septic cases with 31 survivals and 12 deaths. The variables that had the highest discriminatory power were: n(o) of compromised systems, the SNAP, FiO2, and (A-a)O2. The study of these and others variables, such as birth weight, n(o) of risk factors, and pH using a Linear Discriminant Function(LDF) allowed us to identify the high-risk neonates for death with a low error rate (8.33%). The LDF was: F = 0.00043 (birth weight) + 0.30367 (n(o) of risk factors) - 0.1171 (n(o) of compromised systems) + 0.33223 (SNAP) + 2.27972 (pH) - 14.96511 (FiO2) + 0.01814 ((A-a)O2). If F > 22.77 there was high risk of death. This study suggests that the LDF at the onset of sepsis is useful for the early identification of the high-risk neonates that need special clinical and laboratory surveillance.

Stability of cp-Ti and Ti-6Al-4V alloy for dental implants as a function of saliva pH - an electrochemical study

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Higher salt preference in heart failure patients

Heart failure (HF) is a complex syndrome that involves changes in behavioral, neural and endocrine regulatory systems. Dietary salt restriction along with pharmacotherapy is considered an essential component in the effective management of symptomatic HF patients. However, it is well recognized that HF patients typically have great difficulty in restricting sodium intake. We hypothesized that under HF altered activity in systems that normally function to regulate body fluid and cardiovascular homeostasis could produce an increased preference for the taste of salt. Therefore, this study was conducted to evaluate the perceived palatability (defined as salt preference) of food with different concentrations of added salt in compensated chronically medicated HF patients and comparable control subjects. Healthy volunteers (n = 25) and medicated, clinically stable HF patients (n = 38, NYHA functional class II or III) were interviewed and given an evaluation to assess their preferences for different amounts of saltiness. Three salt concentrations (0.58, 0.82, and 1.16 g/100 g) of bean soup were presented to the subjects. Salt preference for each concentration was quantified using an adjective scale (unpleasant, fair or delicious). Healthy volunteers preferred the soup with medium salt concentration (p = 0.042), HF patients disliked the low concentration (p < 0.001) and preferred the high concentration of salted bean soup (p < 0.001). When compared to healthy volunteers, HF patients demonstrated a significantly greater preference for the soup with a high salt concentration (p = 0.038). It is concluded that medicated, compensated patients under chronic treatment for HF have an increased preference for salt. (C) 2011 Elsevier Ltd. All rights reserved,

Survival rate, body size and food abundance in pure and mixed blowfly cultures

The influence of food abundance, larval density and interspecific interactions on the survival and body size of Chrysomya albiceps, Chrysomya megacephala and Cochliomyia macellaria was investigated in pure and mixed cultures, to determine the impact of competition and/or facultative predation on native and introduced blowfly species in South America. In mixed cultures there was complete elimination of C. megacephala and C. macellaria. Chrysomya albiceps exhibited higher survival in mixed compared to pure cultures, suggesting that predation offers more advantages than competition for food. Body size of C. albiceps was significantly affected by food scarcity in pure cultures. However, tibia size in males of all species suffered no significant variation as a function of food scarcity. The implications of these results for population dynamics of introduced and native blowfly species are discussed.

Echocardiographic detection of congestive heart failure in postinfarction rats

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Respiratory pressures and expiratory peak flow rate of patients undergoing coronary artery bypass graft surgery

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Growth hormone attenuates skeletal muscle changes in experimental chronic heart failure

Objective: This study evaluated the effects of growth hormone (GH) on morphology and myogenic regulatory factors (MRF) gene expression in skeletal muscle of rats with ascending aortic stenosis (AAS) induced chronic heart failure.Design: Male 90-100 g Wistar rats were subjected to thoracotomy. AAS was created by placing a stainless-steel clip on the ascending aorta. Twenty five weeks after surgery, rats were treated with daily subcutaneous injections of recombinant human GH (2 mg/kg/day; AAS-GH group) or saline (AAS group) for 14 days. Sham-operated animals served as controls. Left ventricular (LV) function was assessed before and after treatment. IGF-1 serum levels were measured by ELISA. After anesthesia, soleus muscle was frozen in liquid nitrogen. Histological sections were stained with HE and picrosirius red to calculate muscle fiber cross-sectional area and collagen fractional area, respectively. MRF myogenin and MyoD expression was analyzed by reverse transcription PCR.Results: Body weight was similar between groups. AAS and AAS-GH groups presented dilated left atrium, left ventricular (LV) hypertrophy (LV mass index: Control 1.90 +/- 0.15; AAS 3.11 +/- 0.44; AAS-GH 2.94 +/- 0.47 g/kg; p < 0.05 AAS and AAS-GH vs. Control), and reduced LV posterior wall shortening velocity. Soleus muscle fiber area was significantly lower in AAS than in Control and AAS-GH groups; there was no difference between AAS-GH and Control groups. Collagen fractional area was significantly higher in MS than Control; AAS-GH did not differ from both Control and AAS groups. Serum IGF-1 levels decreased in AAS compared to Control. MyoD mRNA was significantly higher in AAS-GH than AAS; there was no difference between AAS-GH and Control groups. Myogenin mRNA levels were similar between groups.Conclusion: In rats with aortic stenosis-induced heart failure, growth hormone administration increases MyoD gene expression above non-treated animal levels, preserves muscular trophism and attenuates interstitial fibrosis. These results suggest that growth hormone may have a potential role as an adjuvant therapy for chronic heart failure. (C) 2009 Elsevier Ltd. All rights reserved.

Influence of Taurine on Cardiac Remodeling Induced by Tobacco Smoke Exposure

Background/Aims: To investigate the effect of taurine on cardiac remodeling induced by smoking. Methods: In the first step, rats were allocated into two groups: Group C (n=14): control; Group T (n=14): treated with taurine (3% in drinking water), for three months. In the second step, rats were allocated into two groups: Group ETS (n=9): rats exposed to tobacco smoke; Group ETS-T (n=9): rats exposed to tobacco smoke and treated with taurine for two months. Results: After three months, taurine presented no effects on morphological or functional variables of normal rats assessed by echocardiogram. on the other hand, after two months, ETS-T group presented higher LV wall thickness (ETS=1.30 (1.20-1.42); ETS-T=1.50 (1.40-1.50); p=0.029), E/A ratio (ETS=1.13 +/- 0.13; ETS-T=1.37 +/- 0.26; p=0.028), and isovolumetric relaxation time normalized for heart rate (ETS=53.9 +/- 4.33; ETS-T=72.5 +/- 12.0; p<0.001). The cardiac activity of the lactate dehydrogenase was higher in the ETS-T group (ETS=204 +/- 14 nmol/mg protein; ETS-T=232 +/- 12 nmol/mg protein; p<0.001). ETS-T group presented lower levels of phospholamban (ETS=1.00 +/- 0.13; ETS-T=0.82 +/- 0.06; p=0.026), phosphorylated phospholamban at Ser16 (ETS=1.00 +/- 0.14;ETS-T=0.63 +/- 0.10;p=0.003), and phosphorylated phosfolamban/phospholamban ratio (ETS=1.01 +/- 0.17; ETS-T=0.77 +/- 0.11; p=0.050). Conclusion: In normal rats, taurine produces no effects on cardiac morphological or functional variables. on the other hand, in rats exposed to cigarette smoke, taurine supplementation increases wall thickness and worsens diastolic function, associated with alterations in calcium handling protein and cardiac energy metabolism. Copyright (C) 2011 S. Karger AG, Basel

Myostatin and follistatin expression in skeletal muscles of rats with chronic heart failure

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