Hiroshi Sunagawa

Elevated levels of plasma endothelin-1 in young patients with pulmonary hypertension caused by congenital heart disease are decreased after successful surgical repair.

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Influence of pulmonary blood pressure and flow on endothelin-1 production in humans

Summary: To investigate the regulation of endothelin-1 (ET-1) production, cardiac catheterization was performed in young patients with congenital heart disease (27 ± 5 months old, mean ± SEM), and plasma levels of ET-1 in the inferior vena cava were measured by a sandwich-enzyme immunoassay. Plasma ET-1 levels of age-matched healthy controls were 1.55 ± 0.07 pg/ml (n = 6). In patients with atrial septal defect [without pulmonary hypertension (PH)] who had volume but not pressure overload to the pulmonary circulation (PC), plasma ET-1 levels were significantly lower than in controls. In patients with PH due to ventricular septal defect (VSD) who had both volume and pressure overload to PC, the levels were significantly higher than in controls. In patients with PH and severe pulmonary congestion due to pulmonary venous stenosis (PVS), plasma ET-1 levels were significantly higher than in those with VSD, suggesting that ET-1 production is also augmented by pulmonary congestion. The present findings suggest that ET-1 production is increased by pressure overload to PC but decreased by volume overload to PC.

Abnormal neurohumoral responses to exercise in patients with heart disease : Inhibition of an increase in endothelin-1 production during exercise

We have reported that the plasma endothelin-1 (ET-1) level is significantly increased by exercise in healthy athletes and that it is elevated in the circulation of the non-working leg but not the working leg, suggesting that ET-1 plays an important role in redistribution of blood during exercise. This study was designed to compare alterations of neurohumoral substances by exercise in normal subjects and patients with heart disease. Study patients comprised three groups: eight patients with congestive heart failure (CHF) due to Ebsteins anomaly or single-ventricle heart after Fontan operation; six patients with complete transposition of the great arteries (TGA) after an anatomic surgical correction who may be candidates for ischemic heart disease; and five age-matched normal subjects. All patients were in New York Heart Association functional class I. All subjects performed symptom-limited treadmill exercise. It is suggested that patients with CHF or TGA have a manifest or latent exercise intolerance, respectively. In failed to increase plasma ET-1 level, although it caused a greater increase in norepinephrine, angiotensin II, and arginine vasopressin than in the controls. Exercise also caused a delay in the increased response of plasma ET-1 levels in patients with TGA after an anatomic surgical repair. On the other hand, plasma brain natriuretic peptide (BNP) level was augmented by exercise in patients with CHF and patients with TGA but not in the controls. The present results suggest that an increase in ET-1 production during exercise is absent in patients with heart disease. The mechanisms of inhibition of ET-1 production during exercise in patients with heart disease remain to be elucidated. However, the present study suggests that ET-1 plays an important role in redistribution of blood during exercise, and proposes the possibility that failure of an increase in ET-1 production results in exercise intolerance in patients with heart disease.

Cardiodynamic effects of experimental right bundle branch block in canine hearts with normal and hypertrophied right ventricles

Cardiodynamic effects of acute experimental right bundle branch block (RBBB) were studied in canine hearts: group A included 15 normal hearts; group B-1 had seven hearts with mild right ventricular hypertrophy (RVH), and group B-2 had 11 hearts with marked RVH. The main sequential changes following RBBB were marked prolongation of the Q upstroke interval of the right ventricle and striking shortening of right ventricular systolic time that affected right and left ventricular interaction, particularly in the hearts with RVH. Hemodynamic changes were: the right ventricular end-diastolic pressure was elevated markedly (4.4 +/- 2.2----9.8 +/- 2.6 mm Hg, p less than 0.001) in group B-2, moderately (p less than 0.01) in group B-1, and not at all in group A. The right ventricular positive peak dp/dt decreased remarkably (1036 +/- 151----827 +/- 152 mm Hg/sec, p less than 0.001) in group B-2 and negligibly in the other groups. A significant correlation existed between the percentage of decrease in right ventricular peak dp/dt and the QRS duration of RBBB in each group (p less than 0.01). The left ventricular peak negative dp/dt decreased distinctly (2570 +/- 326----+/- 2055 +/- 362 mm Hg/sec, p less than 0.01) in group B-2 and not at all in the other groups. The stroke volume showed 12% decrease in group B-2 (p less than 0.001), 8% decrease in group B-1 (NS), and no decrease in group A. In the presence of RVH, acute RBBB causes significant impairment of right and left ventricular function. The magnitude of the impairment invariably depends upon both the prior degree of RVH and the width of the QRS complex.

Plasma endothelin-1 levels after exercise in patients with congenital heart disease

Summary: We have previously reported that plasma endothelin-1 (ET-1) levels were significantly increased after exercise in healthy athletes. In the present study, venous plasma ET-1 levels were measured to investigate whether the role of ET-1 during exercise differs between healthy athletes and patients with congenital heart disease. Seven patients (mean age 13 years) performed symptom-limited treadmill exercise (Bruce protocol). All patients were in class I of the NYHA functional classification. The mean end-exercise 02 utilization was 32 ml/min/kg (166% of ventilatory threshold). Blood sampling was carried out in the seated position. The plasma ET-1 level was 1.21 pg/ml before exercise and did not alter immediately after or 30 min after exercise. The plasma level of norepinephrine was markedly elevated immediately after exercise and returned to the basal level 30 min after exercise. The present study demonstrated that exercise failed to alter plasma ET-1 levels in patients with congenital heart disease.