Assesment of the TEI index of myocardial performance in dogs with doxorubicin-induced cardiomiopathy

The development of a dose-dependent cardiomyopathy is the main limitation for the use of doxorubicin in chemotherapy protocols in both humans and animals. In this setting, the global myocardial function may be compromised resulting in signs of congestive heart failure. In this study, we investigated the ability of the Tei index of myocardial performance to identify myocardial dysfunction in healthy dogs receiving doxorubicin to a cumulative dose of 210 mg/m(2) over 147 days, comparing it with other standard echocardiographic indicators of systolic and diastolic function. Our results indicated that the Tei index, the isovolumic relaxation time, pre-ejection period and the pre-ejection period-to-left ventricular ejection time ratio were able to identify the cardiotoxic effects of doxorubicin on cardiac function when only 60 mg/m(2) had been administered, while the standard systolic and diastolic parameters, including left ventricular diameter at systole, ejection fraction, and fractional shortening needed at least 120 mg/mg(2) to deteriorate. We concluded that prolonged anthracycline therapy compromises both systolic and diastolic functions, which may be documented earlier by including the Tel index evaluation to the standard echocardiographic assessment of animals receiving doxorubicin.

Rutin administration attenuates myocardial dysfunction in diabetic rats

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Low intensity physical exercise attenuates cardiac remodeling and myocardial oxidative stress and dysfunction in diabetic rats

We evaluated the effects of a low intensity aerobic exercise protocol on cardiac remodeling and myocardial function in diabetic rats. Wistar rats were assigned into four groups: sedentary control (C-Sed), exercised control (C-Ex), sedentary diabetes (DM-Sed), and exercised diabetes (DM-Ex). Diabetes was induced by intraperitoneal injection of streptozotocin. Rats exercised for 9 weeks in treadmill at 11 m/min, 18 min/day. Myocardial function was evaluated in left ventricular (LV) papillary muscles and oxidative stress in LV tissue. Statistical analysis was given by ANOVA or Kruskal-Wallis. Echocardiogram showed diabetic groups with higher LV diastolic diameter-to-body weight ratio and lower posterior wall shortening velocity than controls. Left atrium diameter was lower in DM-Ex than DM-Sed (C-Sed: 5.73 ± 0.49; C-Ex: 5.67 ± 0.53; DM-Sed: 6.41 ± 0.54; DM-Ex: 5.81 ± 0.50 mm; P < 0.05 DM-Sed vs C-Sed and DM-Ex). Papillary muscle function was depressed in DM-Sed compared to C-Sed. Exercise attenuated this change in DM-Ex. Lipid hydroperoxide concentration was higher in DM-Sed than C-Sed and DM-Ex. Catalase and superoxide dismutase activities were lower in diabetics than controls and higher in DM-Ex than DM-Sed. Glutathione peroxidase activity was lower in DM-Sed than C-Sed and DM-Ex. Conclusion. Low intensity exercise attenuates left atrium dilation and myocardial oxidative stress and dysfunction in type 1 diabetic rats.

Myocardial performance in conscious streptozotocin diabetic rats

Abstract Background In spite of a large amount of studies in anesthetized animals, isolated hearts, and in vitro cardiomyocytes, to our knowledge, myocardial function was never studied in conscious diabetic rats. Myocardial performance and the response to stress caused by dobutamine were examined in conscious rats, fifteen days after the onset of diabetes caused by streptozotocin (STZ). The protective effect of insulin was also investigated in STZ-diabetic rats. Methods Cardiac contractility and relaxation were evaluated by means of maximum positive (+dP/dtmax) and negative (-dP/dtmax) values of first derivative of left ventricular pressure over time. In addition, it was examined the myocardial response to stress caused by two dosages (1 and 15 μg/kg) of dobutamine. One-way analysis of variance (ANOVA) was used to compare differences among groups, and two-way ANOVA for repeated measure, followed by Tukey post hoc test, to compare the responses to dobutamine. Differences were considered significant if P < 0.05. Results Basal mean arterial pressure, heart rate, +dP/dtmax and -dP/dtmax were found decreased in STZ-diabetic rats, but unaltered in control rats treated with vehicle and STZ-diabetic rats treated with insulin. Therefore, insulin prevented the hemodynamic and myocardial function alterations observed in STZ-diabetic rats. Lower dosage of dobutamine increased heart rate, +dP/dtmax and -dP/dtmax only in STZ-diabetic rats, while the higher dosage promoted greater, but similar, responses in the three groups. In conclusion, the results indicate that myocardial function was remarkably attenuated in conscious STZ-diabetic rats. In addition, the lower dosage of dobutamine uncovered a greater responsiveness of the myocardium of STZ-diabetic rats. Insulin preserved myocardial function and the integrity of the response to dobutamine of STZ-diabetic rats. Conclusion The present study provides new data from conscious rats showing that the cardiomyopathy of this pathophysiological condition was expressed by low indices of contractility and relaxation. In addition, it was also demonstrated that these pathophysiological features were prevented by the treatment with insulin.

Early Diagnosis of Myocardial Dysfunction in Patients With Hematological Malignancies Submitted to Chemotherapy. Preliminary Results.

Early Diagnosis of Miocardial Dysfunction in Patients with Hematological Malignancies Submitted to Chemotherapy. Preliminary Background: Considering the current diagnostic improvements and tl1erapeutic approaches, patients witl 1 cancer can now be healed or keep the disease under control, still, the chemotherapy may cause heart damage, evolving to Congestive Heart Failure. Recognition of those changes increases the chances of control the endpoints; hence, new parameters of cardiac and fluid mechanics analysis have been used to assess the myocardial function, pursuing an earlier diagnosis of the cardiac alterations. This study aimed to detect early cardiac dysfunction consequently to chemotherapy in patients with hematological malignancies (HM). Methods: Patients with leukemia and lymphoma, submitted to chemotherapy, without knowing heart diseases were studied. Healthy volunteers served as the control group. Conventional 2DE parameters of myocardial function were analyzed. The peak global longitudinal, circumferential and radial left ventricular (LV) strain were deternined by 2D and 3D speckle tracking (STE); peak area strain measured by 3D STE and LV torsionn, twisting rate, recoil / recoil rate assessed by 2D STE. The LV vortex formation time (VFT) during the rapid diastolic filling was estimated by the 2D mitral valve (MV) planimetry and Pulsed Doppler LV inflow by: VFT- 4(1-β) / π x α3 x LVEF Where 1- β is the E wave contribution to the LV stroke volume and α3 is a volumetric variable related to the MV area. The statistical level was settled on 5%. Results: See Table. Conclusion: Despite the differences between the two groups concerning the LVESV, LVEF and E´, those parameters still are in the normal range when considering the patients submitted to chemotherapy; thus, in the clinical setting, they are not so noticeable. The 3D GLS was smaller among the patients, oppositely to the 2D GLS, suggesting that the former variable is more accurate to assess tlhe LV systolic function. The VFT is a dimensionless measure of the optimal vortex development inside the LV chamber; reflecting the efficiency of the diastolic filling and, consequently, blood ejection. This index showed to be diminished in patients with HM submitted to chemotherapy, indicating an impairment of the in1pulse and thrust, hence appearing to be a very early marker of diastolic and systolic dysfunction in this group.

Inhibition of caspase 1 reduces human myocardial ischemic dysfunction via inhibition of IL-18 and IL-1β

The proinflammatory cytokine IL-18 was investigated for its role in human myocardial function. An ischemia/reperfusion (I/R) model of suprafused human atrial myocardium was used to assess myocardial contractile force. Addition of IL-18 binding protein (IL-18BP), the constitutive inhibitor of IL-18 activity, to the perifusate during and after I/R resulted in improved contractile function after I/R from 35% of control to 76% with IL-18BP. IL-18BP treatment also preserved intracellular tissue creatine kinase levels (by 420%). Steady-state mRNA levels for IL-18 were elevated after I/R, and the concentration of IL-18 in myocardial homogenates was increased (control, 5.8 pg/mg vs. I/R, 26 pg/mg; P < 0.01). Active IL-18 requires cleavage of its precursor form by the IL-1β-converting enzyme (caspase 1); inhibition of caspase 1 also attenuated the depression in contractile force after I/R (from 35% of control to 75.8% in treated atrial muscle; P < 0.01). Because caspase 1 also cleaves the precursor IL-1β, IL-1 receptor blockade was accomplished by using the IL-1 receptor antagonist. IL-1 receptor antagonist added to the perifusate also resulted in a reduction of ischemia-induced contractile dysfunction. These studies demonstrate that endogenous IL-18 and IL-1β play a significant role in I/R-induced human myocardial injury and that inhibition of caspase 1 reduces the processing of endogenous precursors of IL-18 and IL-1β and thereby prevents ischemia-induced myocardial dysfunction.

Effect of aldosterone antagonism on myocardial dysfunction in hypertensive patients with diastolic heart failure

Background - Specific treatments targeting the pathophysiology of hypertensive heart disease are lacking. As aldosterone has been implicated in the genesis of myocardial fibrosis, hypertrophy, and dysfunction, we sought to determine the effects of aldosterone antagonism on myocardial function in hypertensive patients with suspected diastolic heart failure by using sensitive quantitative echocardiographic techniques in a randomized, double-blinded, placebo-controlled study. Methods and Results - Thirty medically treated ambulatory hypertensive patients (19 women, age 62 +/- 6 years) with exertional dyspnea, ejection fraction >50%, and diastolic dysfunction (E/A 250m/sec) and without ischemia were randomized to spironolactone 25 mg/d or placebo for 6 months. Patients were overweight (31 +/- 5 kg/m(2)) with reduced treadmill exercise capacity (6.7 +/- 2.1 METS). Long-axis strain rate (SR), peak systolic strain, and cyclic variation of integrated backscatter (CVIB) were averaged from 6 walls in 3 standard apical views. Mean 24-hour ambulatory blood pressure at baseline (133 +/- 17/80 +/- 7mm Hg) did not change in either group. Values for SR, peak systolic strain, and CVIB were similar between groups at baseline and remained unchanged with placebo. Spironolactone therapy was associated with increases in SR (baseline: -1.57 +/- 0.46 s(-1) versus 6-months: -1.91 +/- 0.36 s(-1), P < 0.01), peak systolic strain (-20.3 &PLUSMN; 5.0% versus -26.9 &PLUSMN; 4.3%, P < 0.001), and CVIB (7.4 +/- 1.7dB versus 8.6 +/- 1.7 dB, P = 0.08). Each parameter was significantly greater in the spironolactone group compared with placebo at 6 months (P = 0.05, P = 0.02, and P = 0.02, respectively), and the increases remained significant after adjusting for baseline differences. The increase in strain was independent of changes in blood pressure with intervention. The spironolactone group also exhibited reduction in posterior wall thickness (P = 0.04) and a trend to reduced left atrial area (P = 0.09). Conclusions - Aldosterone antagonism improves myocardial function in hypertensive heart disease.

Myocardial and vascular dysfunction and exercise capacity in the metabolic syndrome

The metabolic syndrome (MS) is associated with cardiovascular risk exceeding that expected from atherosclerotic risk factors, but the mechanism of this association is unclear. We sought to determine the effects of the MS on myocardial and vascular function and cardiorespiratory fitness in 393 subjects with significant risk factors but no cardiovascular disease and negative stress echocardiographic findings. Myocardial function was assessed by global strain rate, strain, and regional systolic velocity (s(m)) and diastolic velocity (e(m)) using tissue Doppler imaging. Arterial compliance was assessed using the pulse pressure method, involving simultaneous radial applanation tonometry and echocardiographic measurement of stroke volume. Exercise capacity was measured by expired gas analysis. Significant and incremental variations in left ventricular systolic (s(m), global strain, and strain rate) and diastolic (e(m)) function were found according to the number of components of MS (p <0.001). MS contributed to reduced systolic and diastolic function even in those without left ventricular hypertrophy (p <0.01). A similar dose-response association was present between the number of components of the MS and exercise capacity (p <0.001) and arterial compliance. The global strain rate and em were independent predictors of exercise capacity. In conclusion, subclinical left ventricular dysfunction corresponded to the degree of metabolic burden, and these myocardial changes were associated with reduced cardiorespiratory fitness.' Subjects with MS who also have subclinical myocardial abnormalities and reduced cardiorespiratory fitness may have a higher risk of cardiovascular disease events and heart failure. (C) 2005 Elsevier Inc. All rights reserved.

Insulin resistance is a determinant of myocardial dysfunction in apparently healthy obese subjects

Background. Obese pts have subclinical myocardial dysfunction that may account for their risk of heart failure. We sought the contribution of insulin resistance (IR) to myocardial dysfunction in obesity. Methods. Asymptomatic obese subjects without known cardiac disease underwent clinical evaluation, homeostasis model assessment (HOMA score) as a measure of insulin sensitivity and echocardiographic assessment. After exclusion of DM, overt myocardial dysfunction or ischemia, subclinical myocardial function was assessed by myocardial systolic (Sm) and diastolic velocity (Em) in 79 pts. Association was sought between myocardial function with clinical and biochemical characteristics. Results HOMA score categorized 36 pts as non-IR (HOMA

B-type natriuretic peptide concentrations and myocardial dysfunction in critical illness

B-type natriuretic peptide (BNP) is the first biomarker of proven value in screening for left ventricular dysfunction. The availability of point-of-care testing has escalated clinical interest and the resultant research is defining a role for BNP in the investigation and treatment of critically ill patients. This review was undertaken with the aim of collecting and assimilating current evidence regarding the use of BNP assay in the evaluation of myocardial dysfunction in critically ill humans. The information is presented in a format based upon organ system and disease category. BNP assay has been studied in a spectrum of clinical conditions ranging from acute dyspnoea to subarachnoid haemorrhage. Its role in diagnosis, assessment of disease severity, risk stratification and prognostic evaluation of cardiac dysfunction appears promising, but requires further elaboration. The heterogeneity of the critically ill population appears to warrant a range of cut-off values. Research addressing progressive changes in BNP concentration is hindered by infrequent assay and appears unlikely to reflect the critically ill patient's rapidly changing haemodynamics. Multi-marker strategies may prove valuable in prognostication and evaluation of therapy in a greater variety of illnesses. Scant data exist regarding the use of BNP assay to alter therapy or outcome. It appears that BNP assay offers complementary information to conventional approaches for the evaluation of cardiac dysfunction. Continued research should augment the validity of BNP assay in the evaluation of myocardial function in patients with life-threatening illness.

Noninvasive Evaluation of Myocardial Systolic Dysfunction in the Early Stage of Kawasaki Disease: A Speckle-Tracking Echocardiography Study

Background: Evaluation of myocardial function by speckle-tracking echocardiography is a new method for the early diagnosis of systolic dysfunction. Objectives: We aimed to determine myocardial speckle-tracking echocardiography indices in Kawasaki Disease (KD) patients and compare them with the same indices in control subjects. Patients and Methods: Thirty-two patients (65.5% males) with KD and 19 control subjects with normal echocardiography participated in this study. After their demographic characteristics and clinical findings were recorded, all the participants underwent transthoracic echocardiography. Strain (S), Strain Rate (SR), Time to Peak Strain (TPS), and Strain Rate (TPSR), longitudinal velocity and view point velocity images in the two, three, and four-chamber views were semi-automatically obtained via speckle-tracking echocardiography. Results: Among the patients, Twenty-four cases (75%) were younger than 4 years. Mean global S and SR was significantly reduced in the KD patients compared to controls (17.03 ± 1.28 vs. 20.22 ± 2.14% and 1.66 ± 0.16 vs. 1.97 ± 0.25 1/second, respectively), while there were no significant differences regarding mean TPS, TPSR, longitudinal velocity and view point velocity. Using repeated measure of analysis of variances, we observed that S and SR decreased from base to apical level in both groups. The change in the pattern of age adjusted mean S and SR across levels was significantly different between the groups (P < 0.001 for both parameters). Conclusions: We showed changes in S and SR assessed in KD patients versus control subjects in the acute phase of KD. However, we suggest that further studies be undertaken to compare S and SR in the acute phase and thereafter in KD patients.

Quantification of Regional Left and Right Ventricular Deformation Indices in Healthy Neonates by Using Strain Rate and Strain Imaging

Background: Color Doppler myocardial imaging (CDMI) allows the calculation of local longitudinal or radial strain rate (SR) and strain (epsilon). The aims of this study were to determine the feasibility and reproducibility of longitudinal and radial SR and epsilon in neonates during the first hours of life and to establish reference values. Methods: Data were obtained from 55 healthy neonates (29 male; mean age, 20 +/- 14 hours; mean birth weight, 3,174 +/- 374 g). Apical and parasternal views quantified regional longitudinal and radial SR and epsilon in differing ventricular wall segments. Values at peak systole, early diastole, and late diastole were calculated from the extracted curves. CDMI data acquired at 300 +/- 50 frames/s were analyzed offline. Three consecutive cardiac cycles were measured during normal respiration. The timing of specific systolic or diastolic regional events was determined. Multiple comparisons between walls and segments were made. Results: Left ventricular (LV) longitudinal deformation showed basal differences compared with apical segments within one specific wall. Right ventricular (RV) longitudinal deformation was not homogeneous, with significant differences between basal and apical segments. Longitudinal 3 values were higher in the RV free basal and middle wall segments compared with the left ventricle. In the RV free wall apical segment, longitudinal SR and 3 were maximal. LV systolic SR and epsilon values were higher radially compared with longitudinally (radial peak systolic SR midportion, 2.9 +/- 0.6 s(-1); radial peak systolic epsilon 53.8 +/- 19%; longitudinal peak systolic SR midportion, -1.8 +/- 0.5 s(-1); longitudinal peak systolic epsilon, -24.8 +/- 3%; P < .01). Longitudinal systolic epsilon and SR interobserver variability values were 1.2% and 0.7%, respectively. Conclusion: Ultrasound-based SR and 3 imaging is a practical and reproducible clinical technique in neonates, allowing the calculation of regional longitudinal and radial deformation in RV and LV segments. These regional SR and epsilon indices represent new, noninvasive parameters that can quantify normal neonate regional cardiac function. Independent from visual interpretation, they can be used as reference values for diagnosis in ill neonates. (J Am Soc Echocardiogr 2009;22:369-375.)

Relação entre função ventricular esquerda e os índices de captação miocárdio/pulmão em estudos Gated-SPECT

Introdução – A tomografia de emissão de fotão simples sincronizada com o sinal eletrocardiográfico (Gated-SPECT) é essencial para a avaliação conjunta da perfusão e da função ventricular esquerda (VE) do miocárdio. Objetivo – Investigar a relação entre a função VE e o índice de captação (IC) miocárdio/pulmão direito (M/PD) e M/P esquerdo (M/PE) nos estudos Gated-SPECT com 99mTc-Tetrofosmina. Metodologia – Amostra de 32 pacientes que realizaram estudos Gated-SPECT por indicação clínica, sendo subdividida em dois grupos: Grupo I (GI) – pacientes com a informação clínica de enfarte agudo do miocárdio (EAM); Grupo II (GII) – pacientes com a informação clínica de isquemia. Por cada paciente adquiriram-se imagens estáticas torácico-abdominais e dois estudos Gated-SPECT do miocárdio (protocolo de um dia esforço/repouso). Nas imagens estáticas definiram-se regiões de interesse (Regions of interest – ROI) para calcular os IC. Nos estudos Gated-SPECT utilizou-se o software Quantitative Gated SPECT/Quantitative Perfusion SPECT para calcular a Fração de Ejeção do Ventrículo Esquerdo (FEVE). Efetuou-se análise estatística descritiva para caracterização da amostra. Aplicou-se o teste de Spearman para avaliar a correlação entre a FEVE e os IC por grupo de pacientes. O Teste de Willcoxon foi usado para comparar FEVE em repouso e em esforço. Resultados – Nos estudos Gated-SPECT em esforço não se verificou correlação estatisticamente significativa entre a FEVE e os IC, para GI e GII; em repouso existe correlação positiva estatisticamente significativa entre a FEVE e os IC, para GI; para GII não se verificou correlação. Na comparação dos valores de FEVE em esforço e repouso nos dois grupos constatou-se a existência de diferenças estatisticamente significativas, sendo a FEVE em Esforço

Avaliação da função ventricular esquerda por ecocardiografia bidimensional com VVI em indivíduos hipertensos voluntários

Mestrado em Tecnologia de Diagnóstico e Intervenção Cardiovascular - Ramo de especialização: Ultrassonografia Cardiovascular

Beta-adrenergic blocking agents in heart failure

Cardiac dysfunction in heart failure is widely recognized as a progressive process, regardless of the clinical signs and symptoms. An increase in cardiac sympathetic drive is one of the earliest neurohormonal responses occurring in patients with heart failure and may be one of the major causes of the progressive remodeling leading to the decline in myocardial function, and responsible for the poor prognosis of patients with heart failure. Therefore, recent data provided by several appropriately designed clinical trials clearly indicate the benefits of beta-adrenoceptor blocking agents, combined with diuretics, ACE inhibitors, and digoxin in chronic heart failure class II to IV due to systolic ventricular dysfunction. The benefits are related to symptoms, functional capacity, remodeling, and improvement in left ventricular function, reduction in cardiovascular hospitalization, a decrease in the overall and sudden cardiac death rate, and are similar in patients with ischemic or nonischemic cardiomyopathy, independent of age, gender, or functional class. In this review we describe the cardiovascular effects of the increase in sympathetic drive, the pharmacological properties of the beta-blockers most evaluated in heart failure therapy (metoprolol, bisoprolol, and carvedilol), the major clinical trials related to these agents in heart failure, the recommendations for their appropriate use in clinical practice, the precautions to be adopted, and how to handle the more common adverse reactions.