Effects of BDF 9198 on left ventricular contractility in advanced spontaneously hypertensive rats with heart failure

In the first part of this study, we characterized 24-month-old Wistar Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs), their heart weights, and the responses of the isolated left ventricles to electrical stimulation. In the main part of the study, we tested whether the positive inotropic effects of BDF 9198, which prevents the closure of the cardiac sodium channel, were present in senescence and heart failure. Thus, we studied the effects of BDF 9198 on the left ventricle strips of 24-month-old WKY rats (senescence) and SHRs using contractility methods. In comparison with WKY rats, the left ventricles of 24-month-old SHRs were hypertrophied and had prolonged times to peak contraction. BDF 9198 (10(-8) to 10(-6) m) was a positive inotrope on the left ventricles of WKY rats, with a maximum augmenting effect of 122% with BDF 9198 at 10(-7) m. The magnitude of the augmenting effects of BDF 9198 were reduced in SHR heart failure, with a maximum augmenting effect of 26% at 10(-7) m. BDF 9198 at 10(-6) m attenuated the responses of the SHR left ventricle to electrical stimulation. In conclusion, the potential of drugs that prevent closure of the sodium channel as positive inotropes in the treatment of heart failure should be further considered.

Left ventricular dyssynchrony predicts benefit of cardiac resynchronization therapy in patients with end-stage heart failure before pacemaker implantation

We evaluated patients with end-stage heart failure who have a high likelihood of response to cardiac resynchronization therapy (biventricular pacing). It appears that 20% of patients do not respond to this expensive therapy despite the use of selection criteria (dilated cardiomyopathy, heart failure, New York Heart Association class II or IV, left ventricular election fraction 120 ms). The presence of left ventricular dys-synchrony is needed to result in improvement after cardiac resynchronization therapy. (C)2003 by Excerpta Medica, Inc.

Usefulness of myocardial tissue Doppler echocardiography to evaluate left ventricular dyssynchrony before and after biventricular pacing in patients with idiopathic dilated cardiomyopathy

Tissue Doppler imaging allows assessment of left ventricular dyssynchrony and resynchronization after biventricular pacing.

Ventricular dysfunction in early diabetic heart disease: detection, mechanisms and significance

The detection of preclinical heart disease is a new direction in diabetes care. This comment describes the study by Vinereanu and co-workers in this issue of Clinical Science in which tissue Doppler echocardiography has been employed to demonstrate subtle systolic and diastolic dysfunction in Type 11 diabetic patients who had normal global systolic function and were free of coronary artery disease. The aetiology of early ventricular dysfunction in diabetes relates to complex intramyocardial and extramyocardial mechanisms. The initiating event may be due to insulin resistance, and involves abnormal myocardial substrate utilization and uncoupling of mitochondrial oxidative phosphorylation. Dysglycaemia plays an important role via the effects of oxidative stress, protein kinase C activation and advanced glycosylation end-products on inflammatory signalling, collagen metabolism and fibrosis. Extramyocardial mechanisms involve peripheral endothelial dysfunction, arterial stiffening and autonomic neuropathy. The clinical significance of the ventricular abnormalities described is unknown. Confirmation of their prognostic importance for cardiac disease in diabetes would justify routine screening for presymptomatic ventricular dysfunction, as well as clinical trials of novel agents for correcting causal mechanisms. These considerations could also have implications for patients with obesity and the metabolic syndrome.

The left ventricular contractility of the rat heart is modulated by changes in flow and a1-adrenoceptor stimulation

Myocardial contractility depends on several mechanisms such as coronary perfusion pressure (CPP) and flow as well as on a1-adrenoceptor stimulation. Both effects occur during the sympathetic stimulation mediated by norepinephrine. Norepinephrine increases force development in the heart and produces vasoconstriction increasing arterial pressure and, in turn, CPP. The contribution of each of these factors to the increase in myocardial performance needs to be clarified. Thus, in the present study we used two protocols: in the first we measured mean arterial pressure, left ventricular pressure and rate of rise of left ventricular pressure development in anesthetized rats (N = 10) submitted to phenylephrine (PE) stimulation before and after propranolol plus atropine treatment. These observations showed that in vivo a1-adrenergic stimulation increases left ventricular-developed pressure (P<0.05) together with arterial blood pressure (P<0.05). In the second protocol, we measured left ventricular isovolumic systolic pressure (ISP) and CPP in Langendorff constant flow-perfused hearts. The hearts (N = 7) were perfused with increasing flow rates under control conditions and PE or PE + nitroprusside (NP). Both CPP and ISP increased (P<0.01) as a function of flow. CPP changes were not affected by drug treatment but ISP increased (P<0.01). The largest ISP increase was obtained with PE + NP treatment (P<0.01). The results suggest that both mechanisms, i.e., direct stimulation of myocardial a1-adrenoceptors and increased flow, increased cardiac performance acting simultaneously and synergistically.

Influence of reconstruction parameters during filtered backprojection and ordered-subset expectation maximization in the measurement of the left-ventricular volumes and function during gated SPECT

A crucial method for investigating patients with coronary artery disease (CAD) is the calculation of the left ventricular ejection fraction (LVEF). It is, consequently, imperative to precisely estimate the value of LVEF--a process that can be done with myocardial perfusion scintigraphy. Therefore, the present study aimed to establish and compare the estimation performance of the quantitative parameters of the reconstruction methods filtered backprojection (FBP) and ordered-subset expectation maximization (OSEM). Methods: A beating-heart phantom with known values of end-diastolic volume, end-systolic volume, and LVEF was used. Quantitative gated SPECT/quantitative perfusion SPECT software was used to obtain these quantitative parameters in a semiautomatic mode. The Butterworth filter was used in FBP, with the cutoff frequencies between 0.2 and 0.8 cycles per pixel combined with the orders of 5, 10, 15, and 20. Sixty-three reconstructions were performed using 2, 4, 6, 8, 10, 12, and 16 OSEM subsets, combined with several iterations: 2, 4, 6, 8, 10, 12, 16, 32, and 64. Results: With FBP, the values of end-diastolic, end-systolic, and the stroke volumes rise as the cutoff frequency increases, whereas the value of LVEF diminishes. This same pattern is verified with the OSEM reconstruction. However, with OSEM there is a more precise estimation of the quantitative parameters, especially with the combinations 2 iterations × 10 subsets and 2 iterations × 12 subsets. Conclusion: The OSEM reconstruction presents better estimations of the quantitative parameters than does FBP. This study recommends the use of 2 iterations with 10 or 12 subsets for OSEM and a cutoff frequency of 0.5 cycles per pixel with the orders 5, 10, or 15 for FBP as the best estimations for the left ventricular volumes and ejection fraction quantification in myocardial perfusion scintigraphy.

Avaliação ecocardiográfica da função sistólica ventricular direita em doentes com disfunção ventricular esquerda: parâmetros convencionais versus strain bidimensional

Mestrado em Tecnologia de Diagnóstico e Intervenção Cardiovascular.

Time to Left Ventricular Reverse Remodeling after Cardiac Resynchronization Therapy: Better Late than Never

INTRODUCTION: Left ventricular reverse remodeling (LVRR), defined as reduction of end-diastolic and end-systolic dimensions and improvement of ejection fraction, is associated with the prognostic implications of cardiac resynchronization therapy (CRT). The time course of LVRR remains poorly characterized. Nevertheless, it has been suggested that it occurs ≤6 months after CRT. OBJECTIVE: To characterize the long-term echocardiographic and clinical evolution of patients with LVRR occurring >6 months after CRT and to identify predictors of a delayed LVRR response. METHODS: A total of 127 consecutive patients after successful CRT implantation were divided into three groups according to LVRR response: Group A, 19 patients (15%) with LVRR after >6 months (late LVRR); Group B, 58 patients (46%) with LVRR before 6 months (early LVRR); and Group C, 50 patients (39%) without LVRR during follow-up (no LVRR). RESULTS: The late LVRR group was older, more often had ischemic etiology and fewer patients were in NYHA class ≤II. Overall, group A presented LVRR between group B and C. This was also the case with the percentage of clinical response (68.4% vs. 94.8% vs. 38.3%, respectively, p<0.001), and hospital readmissions due to decompensated heart failure (31.6% vs. 12.1% vs. 57.1%, respectively, p<0.001). Ischemic etiology (OR 0.044; p=0.013) and NYHA functional class

Protective effect of left ventricular hypertrophy in right coronary artery occlusions

OBJECTIVE: To test the hypothesis that left ventricular hypertrophy (LVH) reduces the electrocardiographic and functional effects of right coronary artery occlusion. METHODS: We analysed 215 patients (166 males and 49 women,age of 58.9±10.6 years), with occlusion of the right coronary artery without other associated lesions. There was no significant difference (p>0.05) in age and gender distribution between the 78 patients with LVH (left ventricular mass >100g/m²) (Group A) when compared with the 137 patients without LVH (left ventricular mass <100g/m²) (Group B). RESULTS: The electrocardiographic finding of transmural necrosis was more often found in group B patients than in group A patients (56.9% and 30.8%, respectively; p<0.05). The left ventricular function parameters of group A were better than those of group B: the ratio end-diastolic pressure/systolic pressure (EDP/SP) (A: 0.108±0.036; B: 0.121±0.050; p<0.05); the end-diastolic volume index (A: 75.9±31.3ml/m²; B: 88.0±31.0ml/m²; p<0.01); the end-systolic volume index (A: 16.0±10.0ml/m²; B: 27.0 ±20.0ml/m²; p<0.001); the ejection fraction (A 78.6±10.8%; B 67.7±17.9%; p<0.001); the anteroinferior shortening (A: 43.9±10.3%; B: 35.1±12.8%; p<0.001). A higher degree of coronary tortuosity was observed in group A than in group B (78.2% and 24.1%; p<0.001) and also a more frequent absent or minimal diaphragmatic hypokinetic area (A: 80.8%; B: 54.0%; p<0.05). CONCLUSION: LVH reduces the effects of myocardial sequela and protects LV function when right coronary occlusion develops.

Mitral valve disease with rheumatic appearance in the presence of left ventricular endomyocardial fibrosis

This is a report of a nine-year-old boy with both mitral stenosis and regurgitation and extensive endomyocardial fibrosis of the left ventricle. Focus is given to the singularity of the fibrotic process, with an emphasis on the etiopathogenic aspects.

Aortic stenosis. Gender influence on left ventricular geometry and function in patients under 70 years of age

OBJECTIVE: To verify if adaptive left ventricle (LV) characteristics are also present in individuals under 70 years of age with severe aortic stenosis (AS). METHODS: The study comprised 40 consecutive patients under 70 years of age with AS and no associated coronary artery disease, referred for valve surgery. Out of the 40 patients, 22 were men and 18 women, and the mean age was 49.8±14.3 years. Cardiac symptoms, presence of systemic hypertension (SH), functional class according to the New York Heart Association (NYHA), and valve lesion etiology were considered. LV cavity dimensions, ejection fraction (EF), fractional shortening (FS), mass (MS), and relative diastolic thickness (RDT) were examined by Doppler echocardiography. RESULTS: Fourteen (63.6%) men and 11 (61.6%) women were classified as NYHA class III/IV (p=0.70). There was no difference in the frequency of angina, syncope or dyspnea between genders. The incidence of SH was greater in women than in men (10 versus 2, p=0.0044). Women had a smaller LV end-diastolic diameter index (32.1±6.5 x 36.5±5.3mm/m², p=0.027), LV end-systolic diameter index (19.9±5.9 x 26.5±6.4mm/m², p=0.0022) and LV mass index (MS) (211.4±71.1 x 270.9±74.9g/m², p=0.017) when compared with men. EF (66.2±13.4 x 52.0±14.6%, p=0.0032), FS (37.6±10.7 x 27.9±9.6%, p=0.0046) and RDT (0.58±0.22 x 0.44±0.09, p=0.0095) were significantly greater in women than in men. CONCLUSION: It is the patient gender rather than age that influences left ventricular adaptive response to AS.

Comparison between right and left ventricular myocardia during the human fetal period. Stereological evaluation

PURPOSE: To develop a stereological comparison between right (RV) and left ventricle (LV) myocardium during the third human gestational trimester. METHODS: Five human fetal hearts of the third trimester provided representative samples of 5 RV myocardium and 4 LV myocardium. The material was fixed in 10% buffered formaldehyde, and processed through routine methods. Fifteen microscopic fields were randomly chosen and counted in each ventricular myocardium using an "M-42" test system. The following stereological parameters were assessed: Vv (%), Lv (µm²), Sv (µm²/µm³), Vp (µm³), Nv (1/mm³) and total N. RESULTS: No significant difference between the stereological parameters of the myocardial structures assessed was evidenced, when comparing RV and LV. CONCLUSION: Right and left human ventricular myocardium are very similar during the fetal period at least in regard to their structural aspects.

Influence of the elevation of the left ventricular diastolic pressure on the values of the first temporal derivative of the ventricular pressure (dP/dt)

PURPOSE: To assess the effects of the elevation of the left ventricular end-diastolic pressure (LVEDP) on the value of the 1st temporal derivative of the ventricular pressure (dP/dt). METHODS: Nineteen anesthetized dogs were studied. The dogs were mechanically ventilated and underwent thoracotomy with parasympathetic nervous system block. The LVEDP was controlled with the use of a perfusion circuit connected to the left atrium and adjusted to the height of a reservoir. The elevation of the LVEDP was achieved by a sudden increase in the height of a reservoir filled with blood. Continuous recordings of the electrocardiogram, the aortic and ventricular pressures and the dP/dt were performed. RESULTS: Elevation of the LVEDP did not result in any variation of the heart rate (167±16.0bpm, before the procedure; 167±15.5bpm, after the procedure). All the other variables assessed, including systolic blood pressure (128±18.3mmHg and 150±21.5mmHg), diastolic blood pressure (98±16.9mmHg and 115±19.8mmHg), LVEDP (5.5±2.49 and 9.3±3.60mmHg), and dP/dt (4,855 ± 1,082 mmHg/s and 5,149±1,242mmHg/s) showed significant increases following the expansion of the ventricular cavity. Although the elevation of the dP/dt was statistically significant, 6 dogs curiously showed a decrease in the values of dP/dt. CONCLUSION: Sudden elevation of the LVEDP resulted in increased values of dP/dt; however, in some dogs, this response was not uniform.