Acute and long-term haemodynamic and neurohumoral response to nisoldipine vs captopril in patients with heart failure: a randomized double-blind study.

To study the haemodynamic and neurohumoral effects of nisoldipine (2 X 10 mg) vs captopril (3 X 25 mg), 24 patients with heart failure (New York Heart Association class II and III) due to coronary artery disease were treated in a randomized double-blind trial over 3 months. Both drugs were well tolerated. Clinical status was similarly improved in both groups, nisoldipine exerted an additional antiischaemic effect. Nisoldipine lowered the mean arterial pressure and capillary wedge pressure acutely and also after long-term treatment. The increase in cardiac index and stroke volume index, however, which was pronounced after acute administration, was no longer present after 3 months of therapy at rest and was abolished during exercise. Norepinephrine plasma concentration increased after the first dose, plasma renin activity did not change, and aldosterone plasma concentration showed a small insignificant decrease. Urine concentrations of norepinephrine and vasopressin were slightly elevated after the 3-month therapy. After captopril, mean arterial pressure and pulmonary capillary wedge pressure decreased acutely and at follow up. Cardiac index and stroke volume index increased significantly only during exercise at follow-up. Plasma renin activity was significantly elevated and aldosterone plasma concentration only slightly lowered. In contrast to what was seen with nisoldipine, plasma norepinephrine concentration and urine catecholamine and vasopressin concentrations remained unchanged. In conclusion, the pronounced haemodynamic effects seen after the first dose of nisoldipine are mostly abolished after long-term treatment, probably due to neurohumoral counterregulation. The haemodynamic response to captopril is complete only after long-term treatment, without evidence of activation of the neurohumoral systems.

[Morphologic findings in dilated cardiomyopathy and their relation to hemodynamics and catecholamine concentrations in the plasma and myocardium]. / Morphologische Befunde bei der dilatativen Kardiomyopathie und ihre Beziehung zur Hämodynamik und zu den Katecholaminkonzentrationen im Plasma und Myokard.

In 72 patients with dilated cardiomyopathy the degree of morphological alterations were studied by transvenous endomyocardial biopsy. These findings were correlated to the clinical status, left ventricular ejection fraction, and to the catecholamine concentrations in plasma and myocardium. Muscle fiber diameter was negatively correlated to ejection fraction (r = -0.3, p = 0.02) and to the volume fraction of mitochondria (r = -0.32, p = 0.001). Between plasma norepinephrine concentration and ejection fraction a significant negative correlation was found (r = -0.37, p = 0.001). In contrast, myocardial norepinephrine concentration was positively correlated to ejection fraction (r = 0.25, p = 0.04). Between myocardial norepinephrine concentration and muscle fiber diameter a negative correlation was found (r = -0.46, p = 0.004). Patients with an EF of less than 30% and an EF of greater than 45% could be differentiated with an accuracy of 79%, when muscle fiber diameter, plasma norepinephrine concentration, and the density of capillary vessels were entered into a multi-variant analysis. In conclusion, dilated cardiomyopathy is associated with morphological alterations and alterations in plasma and myocardial catecholamine concentrations. Patients with highly reduced ventricular function could be best identified by the combined assessment of plasma catecholamine concentration, muscle fiber diameter, and density of capillary vessels.

[Myocardial noradrenaline content: a factor not considered up to now for the prognosis of patients with dilated cardiomyopathy]. / Myokardialer Noradrenalingehalt: ein bisher nicht berücksichtigter Faktor für die Prognose von Patienten mit dilatativer Kardiomyopathie.

To evaluate the prognosis of patients with idiopathic dilated cardiomyopathy (EF less than 50%) in 55 patients the myocardial catecholamine concentration, plasma catecholamine concentration, and left ventricular ejection fraction were determined. The follow-up time ranged from 7 to 47 months. At the time of follow-up 10 of the 55 patients (group A) had died and three had undergone hearttransplantation. Group A patients had a significant lower EF (27 +/- 10 vs 36 +/- 9%, p less than 0.03), a lower myocardial norepinephrine (254 +/- 168 vs 579 +/- 416 pg/mg, p less than 0.007), higher plasma norepinephrine (640 +/- 333 vs 372 +/- 254 pg/ml, p less than 0.008) and plasma epinephrine (391 +/- 340 vs 116 +/- 81 pg/ml, p less than 0.006) in comparison to patients, who were still alive and not transplanted (group B). Survival was significantly lower in patients with an EF less than 30%, a plasma norepinephrine concentration greater than 350 pg/ml, a plasma epinephrine concentration greater than 125 pg/ml, and a myocardial norepinephrine content less than 400 pg/mg. Cox regression analysis revealed that the ratio of plasma vs myocardial norepinephrine was the best prognostic indicator for patients with an EF less than 30% and this ratio plus the plasma norepinephrine concentration were the best prognostic indicators for the whole group of patients. These data suggest that myocardial norepinephrine content is an important prognostic factor in patients with idiopathic dilated cardiomyopathy.

Relationship between myocardial norepinephrine content and left ventricular function--an endomyocardial biopsy study.

To analyze the relationships between left ventricular function, catecholamine concentrations in plasma and myocardium, and morphological alterations, 20 patients were studied. Fifteen patients had idiopathic dilated cardiomyopathy, and 5 had normal left ventricular function. All patients underwent right ventricular endomyocardial biopsy to determine muscle fibre thickness, percent volume fraction of interstitium, and myocardial catecholamine content. Blood was sampled to measure plasma catecholamine concentrations, and left ventricular cineangiography was performed to determine global ejection fraction. In a simple correlation analysis a significant correlation was found between left ventricular ejection fraction and myocardial norepinephrine content (r = 0.80, P less than 0.001). Left ventricular ejection fraction was negatively correlated with plasma epinephrine concentration (r- = 0.53, P less than 0.02), and with muscle fibre thickness (r = -0.50, P less than 0.03). Myocardial norepinephrine concentration was negatively correlated with plasma epinephrine (r = -0.62, P less than 0.01). Multiple linear regression analysis revealed a strong correlation between myocardial norepinephrine depletion and left ventricular dysfunction, which was independent of all other variables. These data suggest that myocardial norepinephrine depletion determined from right ventricular endomyocardial biopsies strongly correlates with left ventricular dysfunction in idiopathic dilated cardiomyopathy, and seems to be independent of the degree of muscle fibre hypertrophy, volume fraction of interstitium, and of the increased sympathetic tone.

[The clonidine inhibition test: an aid in the diagnosis and postoperative therapeutic control in pheochromocytoma]. / Der Clonidin-Hemmtest: eine Hilfe in der Diagnostik und postoperativen Therapiekontrolle beim Phäochromozytom.

A clonidine-suppression test was carried out in 8 patients with arterial hypertension, raised urinary and plasma catecholamine levels and symptoms suggesting the presence of a pheochromocytoma. In 6 of the patients clonidine reduced the plasma catecholamine concentrations and no pathological findings were seen in the abdominal computed tomogram (CT). In 2 patients noradrenaline levels were excessively high and not lowered by clonidine; in one of these patients the plasma adrenaline concentration was also raised and this too could not be reduced with clonidine. A tumor was detectable in both patients using CT, in one case situated in the left adrenal, in the other extra-medullary. On operation both were found to be a pheochromocytoma. Peritoneal and intra-hepatic metastases were discovered during surgery in the case of the extramedullary localized tumor. The clonidine-suppression test was repeated postoperatively in both patients: it was normal in the case of the completely excised, intramedullary situated tumor but still pathological in the other. Thus the clonidine-suppression test is useful in the diagnosis and post-surgical assessment of pheochromocytoma.