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Biomedical subjects

R Sykulski

Publications and source records attributed to R Sykulski.

At least 19 recordsLinked to original sources

Adaptive changes in the acute haemodynamic effects of cilazapril during chronic treatment. Comparison with long-term clinical effect.

OBJECTIVE: To study the adaptive changes in the acute haemodynamic response to ACE inhibition during chronic treatment in CHF. METHODS: The acute and chronic effects of oral cilazapril (CLZ) treatment, an ACE-inhibitor with prolonged duration on haemodynamic measures (PCWP, PAP, RAP, CI and SVR) and clinical parameters (Quality-of-Life and NYHA class) were investigated in a double-blind, randomised, placebo-controlled trial in CHF. One hundred and thirty five patients (112 completing) in NYHA Classes II-III, on digitalis and diuretic treatment, were randomised after 2 weeks of placebo run-in, to receive either placebo or CLZ 0.5 mg, 1.0 mg or 2.5 mg daily for 12 weeks, followed by 2 week placebo wash-out. Haemodynamic studies, including exercise tests before and 3 h after medication, were performed on the first and last days of treatment. Measurements were performed at rest and at the maximum exercise level. RESULTS: In ACEI-naive patients oral CLZ 0.5 and 1 mg/d caused a dose dependent decrease in PCWP and diastolic PAP, and a significant reduction of SVR mg. A slight increase in CI was observed in all groups. The maximum effect was observed 3-5 h post dose. After 12 weeks of oral treatment, the acute response was similar but was attenuated relative to the first dose. Exercise tolerance improved in a dose dependent manner. The NYHA classification remained unchanged or improved in the majority of patients. Entry into the 2.5 mg group had to be terminated at an early stage due to severe adverse events observed after the first dose. CONCLUSION: During chronic treatment, the haemodynamic response to oral cilazapril was attenuated, indicating that continued clinical improvement in patients with CHF on CLZ is independent of to its acute haemodynamic effects.

Adult↗

Effect of different doses of nasal salmon calcitonin on bone mass.

Forty postmenopausal women with a former Colles' fracture were enrolled in a 1-year study to determine the dose-effect relationship of nasal salmon calcitonin (SCT) on bone mass. They were randomized to receive either placebo, 50, 100, or 200 IU per day of SCT given as a nasal spray. The rate of change in the bone mineral content of the lumbar spine was 0.7, 0.2, 1.1, and 2.0 gHA per year, respectively, and the rate of change in the bone mineral content in the forearm was -0.4, -0.1, 0.0, and -0.1 AU per year, respectively. The rate of change in the bone mineral content of the lumbar spine in patients receiving 200 IU of SCT per day differed significantly from zero (P less than 0.01). Except for one patient, who experienced intolerable nausea, no systemic side effects were observed. Seven patients withdrew, two patients from nasal intolerance to the spray. These preliminary data suggest that SCT given by the nasal route has a positive and dose-dependent effect on spinal bone mass, but affects forearm bone mass only minimally.

Administration, Intranasal↗

Effects of dobutamine and salbutamol on haemodynamics and atrial natriuretic factor in patients with severe congestive heart failure.

The influence of two cardiac inotropic drugs, dobutamine and salbutamol, on plasma atrial natriuretic factor (ANF) was investigated in 20 patients with congestive heart failure. All were in New York Heart Association class-III or IV. The patients underwent right heart catheterization with determination of central pressures, cardiac output, and pulmonary arterial plasma ANF during incremental infusions with dobutamine or salbutamol. Fourteen patients completed the study. Both drugs induced comparable increases in cardiac index and decreases in total systemic vascular resistance (P less than 0.01) without significant changes in central pressures. Heart rate rose after salbutamol (P less than 0.05), but not after dobutamine. No changes in plasma ANF were observed after either of the drug infusions. ANF secretion rate was calculated from simultaneous measurements of ANF in right atrial and pulmonary arterial plasma before and after salbutamol infusion, and median values rose more than seven-fold (P less than 0.05). The results demonstrate that ANF secretion rate is augmented after beta-adrenergic agents, possibly by a direct beta 2-adrenergic stimulation, in patients with severe congestive heart failure, and that changes in plasma ANF are an insufficient measure of ANF release when patient samples are small.

Adult↗

The effect of different doses of nasal salmon calcitonin on plasma cyclic AMP and serum ionized calcium.

To investigate the effect of low doses of intranasal salmon calcitonin on plasma cyclic AMP (cAMP) and serum ionized calcium, 40 healthy postmenopausal women were randomized to receive a single dose of either placebo or 50, 100, or 200 IU of salmon calcitonin as a nasal spray. Blood samples were collected throughout an 8-hour period. None of the doses could provoke detectable hypocalcemia, whereas 100 and 200 IU of salmon calcitonin were associated with an increase in plasma cAMP after 15 minutes. Measurable plasma levels of salmon calcitonin were demonstrated in all active treatment groups, and the calculated areas under the curves showed a dose-dependent increase.

Administration, Inhalation↗

Double-blind comparison of tiapamil and atenolol in patients with mild to moderate hypertension: a multicenter trial.

The efficacy and safety of tiapamil, a new calcium-channel blocker, was compared with the cardio-selective beta-blocker atenolol in a 16-week double-blind, multicenter trial with an initial 4-week placebo run-in period. Eighty-one outpatients with WHO stage I or II hypertension, 55 men and 26 women, entered the study. There was a total of nine drop-outs, six in the tiapamil group and three in the atenolol group. Five were due to side effects (four in the tiapamil group and one in the atenolol group). Sixty-one patients performed a graded exercise test sitting on a ergometer bicycle before and after completion of the therapy. Patients eligible for the study after the placebo period received either tiapamil 450 mg b.i.d. or atenolol 100 mg daily. Both drugs lowered systolic and diastolic blood pressure significantly. After 12 weeks of therapy, supine blood pressure in the tiapamil group fell from 167/104 mmHg to 154/91 mmHg (p less than 0.005), and in the atenolol group from 166/102 mmHg to 151/89 mmHg (p less than 0.005). A satisfactory reduction in diastolic blood pressure, defined as a reduction of more than 10 mmHg and/or values below or equal to 90 mmHg at the end of the study, was achieved in 29 of 35 patients in the tiapamil group and in 27 of 37 in the atenolol group. No changes in heart rate were observed in the tiapamil group, whereas there was a significant fall in heart rate in the atenolol group. The maximal exercise workload tolerated increased equally in both groups, from 135 to 147 watts.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Determinants of atrial natriuretic factor levels in coronary heart disease: significance of central pressures, heart chamber volumes and left ventricular mass.

Atrial natriuretic factor (ANF) was determined in pulmonary and systemic arterial plasma during diagnostic left and right heart catheterization in twenty-three patients. In twenty of these patients ANF was subsequently measured in systemic arterial plasma during nuclear magnetic resonance (NMR) imaging of the heart with computation of left heart chamber volumes and left ventricular mass. Left ventricular end-diastolic pressure was the strongest independent predictor of pulmonary arterial plasma ANF, whereas cardiac index best predicted aortic plasma ANF. Both pulmonary and aortic plasma ANF correlated with systolic and diastolic pulmonary arterial pressure, left ventricular end-diastolic pressure and cardiac index. Left atrial volume index and left ventricular mass index did not correlate with systemic arterial plasma ANF whereas a positive linear correlation between left ventricular end-diastolic volume index and ANF could be demonstrated (r = 0.61, P less than 0.01). Left ventricular end-diastolic volume index was the most important independent predictor of systemic arterial plasma ANF. Systemic arterial plasma ANF might be a simple marker of left ventricular dilatation in patients with heart disease.

Adult↗

Atrial natriuretic peptide during exercise in patients with coronary heart disease before and after single dose atenolol and acebutolol.

Plasma atrial natriuretic peptide (ANP) was measured during dynamic exercise in 10 patients with coronary heart disease before and after single dose atenolol 50 mg and acebutolol 200 mg, respectively. Systolic blood pressure, heart rate and the rate-pressure product increased during exercise before and after beta-blockade, but levels were lower after beta-blockade. Plasma ANP levels at rest were unchanged after atenolol, but rose after acebutolol (p less than 0.01). During exercise plasma ANP increased significantly both before and after beta-blockade, but plasma ANP levels were higher after acebutolol at all workloads (p less than 0.05), whereas plasma ANP levels after atenolol were higher at 125 W exclusively (p less than 0.05). The augmented ANP levels during exercise after beta-blockade probably reflect catecholamine-stimulated ANP release, whereas the elevated plasma ANP levels after acebutolol at rest might be a beta-adrenoceptor-mediated ANP release due to the intrinsic sympathomimetic effect of acebutolol.

Acebutolol↗

Changes in atrial natriuretic factor during preload reduction with nitroglycerin in patients with congestive heart failure.

Nine patients with congestive heart failure, New York Heart Association class II-III, were evaluated with right heart catheterization. Plasma atrial natriuretic factor (ANF) was determined in blood samples from the pulmonary artery simultaneously with recordings of right atrial, pulmonary arterial, pulmonary capillary wedge and systemic arterial pressures and heart rate during preload reduction with 0.5 mg nitroglycerin sublingually. Basal plasma ANF levels were higher in patients with congestive heart failure compared to normal controls, and correlated to right atrial, pulmonary arterial, and pulmonary capillary wedge pressures. After nitroglycerin all patients had reductions in right atrial, pulmonary arterial, and pulmonary capillary wedge pressures and a simultaneous decrease in plasma ANF concentrations, reaching lowest values after 10 min. Central pressures and plasma ANF rose to baseline values within 30 min. After nitroglycerin plasma ANF concentrations correlated to pulmonary arterial and pulmonary capillary wedge pressures, while changes in plasma ANF correlated to changes in right atrial and pulmonary arterial pressures. These results provide further evidence that ANF is released by a pressure-sensitive mechanism and demonstrates that ANF secretion in relation to central pressure variations is preserved in patients with congestive heart failure and that the response is rapid.

Adult↗

Atrial natriuretic factor during exercise in patients with congestive heart failure.

In order to evaluate the potential relationship between atrial pressure development and release of atrial natriuretic factor (ANF), 33 patients with congestive heart failure were investigated with right-sided heart catheterization during supine graded bicycle exercise. Resting plasma ANF levels were higher in patients with heart failure as compared with normal controls, 75.1 +/- 45.6 pmol/l vs 12.3 +/- 6.2 pmol/l (mean +/- SD, N = 33 and N = 42, respectively) and correlated with right atrial, pulmonary arterial and pulmonary capillary wedge pressures. During exercise, central pressures rose steeply with a simultaneous increase in plasma ANF in all patients. Plasma ANF levels correlated with heart rate at a workload of 25 w, to pulmonary arterial and pulmonary capillary wedge pressure at 50 w, and to pulmonary capillary wedge pressure at 75 w. The increments in ANF levels between the different workloads during exercise did not correlate with the corresponding increments in pressure values. In congestive heart failure, the capability of ANF secretion in consequence to pressure stimuli is preserved, and left atrial pressure seems to be the major stimulus for ANF release during exercise.

Adult↗

Changes in plasma atrial natriuretic peptide during exercise in healthy volunteers.

Graded exercise was performed in three healthy volunteers. Plasma levels of immunoreactive atrial natriuretic peptide (iANP) were determined at different workloads. Unchanged or slightly decreased plasma levels of iANP were observed during light exercise, whereas at medium to high workloads a considerable increase in plasma levels of iANP was found. Factors responsible for the increase in plasma levels of iANP might include elevated right atrial pressure and increased plasma levels of epinephrine and norepinephrine.

Adult↗

Electrocardiographic changes in spontaneous left pneumothorax.

A 25-year-old man was admitted with severe chest pain and an electrocardiogram suggestive of anterior myocardial infarction. Echocardiogram was normal, but chest X-ray showed left-sided pneumothorax. The electrocardiogram showed increasing R-wave amplitude in the days after correction of pneumothorax. Taken in the supine position the electrocardiogram can be misleading in case of pneumothorax or mediastinal emphysema, but the electrocardiogram should be normal if taken in the erect position.

Adult↗

Effect of beta 1-adrenoceptor blockade on plasma levels of atrial natriuretic peptide during exercise in normal man.

Increased plasma levels of atrial natriuretic peptide (ANP) during exercise have been reported. To investigate the role of tachycardia as a stimulus for release of ANP during exercise the following study was undertaken. Graded exercise was performed in six healthy volunteers before and after beta 1-adrenoceptor blockade. Plasma levels of ANP were determined at different workloads in both cases. At rest and at all workloads during exercise plasma levels of ANP were higher after beta 1-adrenoceptor blockade than without. Therefore, it is unlikely that tachycardia is a major stimulus for secretion of ANP during exercise. It is suggested that increased right atrial pressure and/or pulmonary arterial blood pressure and increased plasma levels of catecholamines are important secretory stimuli for ANP during exercise.

Adrenergic beta-Antagonists↗

Radio-immunoassay of atrial natriuretic peptide in human plasma.

A highly sensitive and accurate radio-immunoassay for measurement of atrial natriuretic peptide in human plasma has been established. All reagents are commercially available. The sensitivity of the method is 1 pmol/l. The 50% intercept of the standard curve was at 22 fmol/tube and inter- and intra-assay precision were 10.9 and 5.3%, respectively. Plasma immunoreactive atrial natriuretic peptide levels measured in healthy subjects, during pregnancy, and in congestive cardiac failure were within the limits reported in the literature.

Adult↗