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Biomedical subjects

A J Smit

Publications and source records attributed to A J Smit.

At least 127 records · Page 7Linked to original sources
PubMed1990

Dissociation of renal vasodilator and natriuretic effects of dopamine during sulpiride infusion in normal man.

The effect of sulpiride on dopamine-induced changes in renal function in man has been investigated. Dopamine dose-response studies were performed in 7 healthy volunteers before and after sulpiride 200 mg i.v. The same investigations were performed in 15 healthy volunteers after pretreatment with the selective alpha-1-adrenoceptor antagonist prazosin (n = 7) and the non-selective alpha-adrenoceptor-blocker phentolamine (n = 8). Infusion of dopamine 0.25 to 8 micrograms.kg-1.min-1 resulted in a dose-dependent increase in effective renal plasma flow (ERPF) and glomerular filtration rate (GFR), and a fall in filtration fraction (FF) in 7 normal volunteers. Sulpiride had no effect on base-line ERPF or GFR and did not influence the dopamine-induced renal vasodilatation in those volunteers. It did cause a fall in the fractional sodium excretion (FENa+%) from 1.7 to 1.38, and shifted the dose-response curve of the natriuretic response to a subsequent infusion of dopamine. Sulpiride enhanced the fall in diastolic blood pressure during infusion of dopamine. In 7 other volunteers pretreated with prazosin, sulpiride did not influence base-line ERPF, GFR or FF or their response to dopamine, but the sodium excretion fell markedly (FENa+% changed from 1.13 to 0.63). Administration of sulpiride to 8 volunteers after phentolamine pretreatment 20 mg.h-1 i.v. in the first hour followed by 10 mg.h-1 i.v. resulted in a fall in sodium excretion (FENa+% from 1.09 to 0.53) without affecting ERPF or FF, and it did not affect the dose-response curve in the subsequent DA infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Digoxin infusion versus bolus injection in rapid atrial fibrillation: relation between serum level and response.

Using available data on time-concentration and time-effect relationships in normal persons the results of infusion of digoxin in various time periods were simulated and compared with administration of digoxin by bolus injections, using a three-compartment pharmacokinetic model to which a separate small side-effect compartment was subsequently added. The validity of the simulations was tested in 11 patients with rapid atrial fibrillation. Serum digoxin concentrations, ventricular rate and side effects were monitored in a double-blind study comparing an infusion of 1.5 mg digoxin over 6 h with administration of three bolus injections of 0.5 mg digoxin 8 h apart. In agreement with the predictions of the model, the maximal fall in ventricular rate was reached after 8-9 h in the infusion group and after 19-20 h in the bolus injection group, without any detectable difference in side effects. There were certain discrepancies between the results of the clinical study and the predictions of the model, e.g. in serum digoxin concentrations, perhaps due to impaired clearance in the patients. However, it is concluded that the tested model is valid in elderly patients with rapid atrial fibrillation.

Adult↗
PubMed1990

Dopamine in chronic renal failure.

In patients with renal disease a reduced renal vasodilatory but conserved natriuretic response to dopamine is observed. An inverse relationship exists between baseline renal function and the dopamine-induced changes in effective renal plasma flow and glomerular filtration rate over a wide range of dopamine doses. The renal hemodynamic response to dopamine is also impaired in kidney donors. In studies with dopamine antagonists and in measurements of urinary free dopamine excretion no evidence was found for increased endogenous renal dopamine generation in these patients. The response of effective renal plasma flow and filtration fraction to fenoldopam was also impaired. However, the fractional sodium excretion in patients with renal disease was not impaired in both short-term and long-term studies. Perhaps this conserved natriuretic effect is of clinical value in these patients.

Dopamine↗
PubMed1990

Lack of effect of lithium on the renal response to DA1-dopamine receptor stimulation by fenoldopam in normal man.

1. The effect of oral lithium (300 mg) on the renal response to the selective DA1-dopamine receptor agonist fenoldopam was investigated in seven normal men. Lithium had no influence on sodium excretion and renal haemodynamics during fenoldopam infusion. The fenoldopam-induced rise in PRA was enhanced in the presence of lithium. We conclude that a previously described interaction between lithium and the dopamine agonist gludopa is not mediated by DA1-dopamine receptors or is confined to higher doses of lithium.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1990

Efficacy and safety of ibopamine in congestive heart failure.

1. Ibopamine is a new orally active inodilator, which is developed for the treatment of congestive heart failure (CHF). We treated 13 patients with moderate to severe CHF already on maximal conventional medication with ibopamine and studied its effects on haemodynamic parameters, exercise capacity, plasma norepinephrine (NE) and ventricular arrhythmias on ambulatory ECG monitoring. 2. Both cardiac and stroke volume index increased significantly after ibopamine (33% and 35% resp.). These changes were accompanied by a fall in systemic vascular resistance without changes in heart rate or blood pressure. During cardiopulmonary exercise testing, both maximal oxygen consumption and exercise time increased. Plasma NE levels were not significantly changed after ibopamine. Using the Morganroth criteria for proarrhythmia on ambulatory ECG monitoring, two patients showed proarrhythmia from ibopamine, which was not clinically relevant, but four patients had a decrease in ventricular arrhythmias. 3. This study suggests that ibopamine elicits favourable effects on haemodynamics and exercise tolerance in patients with CHF. During ibopamine treatment, there appears to be no increase in ventricular arrhythmias.

Adult↗
PubMed1990

Renal and endocrine effects of fenoldopam and metoclopramide in normal man.

The effects of fenoldopam (FD), a selective dopamine-1 (DA1) agonist in doses from 0.05 to 0.50 micrograms/kg/min and of the aselective dopamine antagonist metoclopramide (MCP) on blood pressure (BP), sodium excretion and renal hemodynamics were investigated in 10 healthy volunteers. During FD infusion the diastolic BP fell 9 mm Hg with a rise in heart rate. During combined infusion of FD and MCP no changes in BP occurred. Effective renal plasma flow rose for all doses of FD with a maximal increase of 36% and was not influenced by MCP infusion. Glomerular filtration rate remained unchanged. FD induced an increase in sodium and calcium excretion compared to placebo study, which was abolished by MCP. A marked rise of plasma renin activity during FD infusion was noted, blunted by MCP. MCP induced a marked increase of aldosterone, sustained, but blunted, during subsequent FD infusion, suggesting a DA1-mediated influence on aldosterone secretion. During infusion of FD alone, an increased urinary dopamine excretion was observed. We conclude that FD induces: (1) systemic and renal vasodilation and (2) natriuresis by direct stimulation of DA1 receptors in the proximal tubule, which is (partially) counteracted by a rise of plasma renin activity and subsequently of aldosterone.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1990

The effect of fenoldopam on renal haemodynamics and natriuresis in chronic renal failure.

The effect of oral administration of fenoldopam, a dopamine-1 receptor agonist, on blood pressure, renal haemodynamics and natriuresis was studied in 12 patients with chronic renal insufficiency. In addition, the effect of administering a low intravenous dose of fenoldopam on top of the oral dose was compared with the effect of the same intravenous dose given immediately before oral fenoldopam. Oral administration of fenoldopam (50 mg t.i.d. for 3 +/- 1 days followed by 100 mg t.i.d. for 8 +/- 1 days) induced a significant fall in blood pressure (median MAP from 107 to 101 mm Hg). Compared to baseline values, body weight, effective renal plasma flow (ERPF), glomerular filtration rate (GFR) and fractional sodium excretion remained unchanged. Infusion of fenoldopam (0.05-0.1 micrograms/kg/min) on day 1 led to a significant fall in blood pressure (median mean arterial pressure from 107.0 to 98.5 mm Hg), and a significant rise in effective renal plasma flow (median ERPF from 132 to 146 ml/min/1.73 m2). Median fractional sodium excretion increased significantly from 2.1 to 3.3%. GFR, filtration fraction and plasma aldosterone concentration did not change. No relationship was found between the fenoldopam-induced changes in ERPF and natriuresis, nor between baseline GFR or ERPF and fenoldopam-induced urinary sodium loss. Infusion of fenoldopam while patients were on oral fenoldopam had no effect on blood pressure, ERPF or GFR. However, again natriuresis was induced, which did not differ significantly from the fenoldopam-induced natriuresis on day 1. We conclude that oral fenoldopam has a moderate blood pressure lowering effect in patients with chronic renal insufficiency, but exerts no effect on ERPF or GFR. Secondly, a fenoldopam-induced natriuresis does not appear to be related to changes in ERPF or aldosterone secretion.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1989

Impaired renal hemodynamic but conserved natriuretic response to dopamine in patients with renal disease.

Renal hemodynamics and sodium excretion were determined before and during infusion of dopamine in doses ranging from 0.25 to 8 micrograms/kg/min in healthy volunteers (n = 15) and in patients with renal disease and moderately impaired renal function (n = 21, baseline glomerular filtration rate 34-85 ml/min). While in normal volunteers dopamine resulted in marked renal vasodilation (maximal fall in filtration fraction 24%), in patients with moderately impaired renal function, the renal vasodilatory response to dopamine was impaired (maximal fall in FF 13%) and was found to depend on baseline glomerular filtration rate. Infusion of dopamine in doses of 2 micrograms/kg/min and higher resulted in an increase in urinary sodium excretion, which was comparable for healthy volunteers and patients with renal disease. We conclude that dopamine results in a predominantly efferent glomerular vasodilation and, therefore, may be salutary in lowering intraglomerular hypertension. However, in patients with renal disease the renal hemodynamic response to dopamine infusion is impaired compared to healthy volunteers, while the natriuretic response is maintained.

Blood Pressure↗
PubMed1988

Effect of metoclopramide on dopamine-induced changes in renal function in healthy controls and in patients with renal disease.

1. The effects of intravenous metoclopramide on baseline values and dopamine dose-response curves for renal haemodynamics and natriuresis were investigated in healthy volunteers and patients with renal disease. 2. Dopamine infusion alone, in doses ranging from 0.25 to 8 micrograms min-1 kg-1, resulted in a dose-dependent increase in effective renal plasma flow (ERPF) and glomerular filtration rate (GFR) with a fall in filtration fraction (FF) in eight hydrated healthy volunteers and, to a lesser degree, in 12 patients with renal disease. An increase in natriuresis (urinary excretion of sodium, UNa+V), fractional excretion of sodium (FENa+) and diuresis (urine flow rate, UV) was found in both groups for doses of 2 micrograms min-1 kg-1 and higher. 3. Metoclopramide infusion did not alter baseline values of GFR, ERPF or FF, but shifted the dopamine dose-response curve for ERPF and FF in the healthy volunteers. Metoclopramide induced a fall in UNa+V and FENa+ in both groups (fall in baseline FENa+ from 1.52 to 0.71 during metoclopramide in healthy volunteers and from 1.23 to 0.56 in patients; P less than 0.01) and blunted the natriuretic response to subsequent dopamine infusion. The fall in UNa+V during metoclopramide infusion showed a strong correlation with baseline GFR (r = -0.944). In the patients, the response for the fractional excretions of beta 2-microglobulin and gamma-glutamyltransferase was comparable with that of FENa+. 4. Dopamine infusion induced a fall, and metoclopramide led to rise, in plasma aldosterone concentration. 5. We conclude that metoclopramide acts as a dopamine antagonist at the renal level in man.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Effect of intravenous infusion of low-dose dopamine on renal function in normal individuals and in patients with renal disease.

A low dose of dopamine was infused in 28 normal volunteers and in 137 patients with varying degrees of renal insufficiency during a routine measurement of the glomerular filtration (GFR) and the effective renal plasma flow (ERPF). Dopamine infusion led to an increase in ERPF and GFR and to fall in the filtration fraction. The effect of dopamine on renal function was most pronounced if the baseline GFR was normal. However, healthy individuals showed greater increases in both ERPF and GFR than renal patients with a comparable baseline GFR. In renal patients no effect was observed if the baseline GFR was below 50 ml/min/1.73 m2. Firstly, it is concluded that already early in renal disease there exists a diminished reserve filtration capacity. Secondly, if the GFR is less than 50 ml/min/1.73 m2, the renal reserve filtration capacity seems to be exhausted.

Dopamine↗
PubMed1984

Cutaneous reactions to captopril. Predictive value of skin tests.

Cutaneous reactions associated with captopril treatment occurred in fifteen out of eighty-nine patients (17%). Dose reduction invariably led to improvement of the reaction but later recurrences were frequent (six patients). In four out of the fifteen patients captopril withdrawal ultimately was necessary. Skin tests and in vitro lymphocyte transformation tests with captopril were performed in these fifteen patients and also in nine captopril-treated control patients without adverse reactions. Positive epicutaneous skin tests were observed in five out of the fifteen patients including the four in whom captopril had to be withdrawn, but in none of the controls. Intracutaneous skin tests were positive in ten of the patients with cutaneous reactions and in two control patients. Captopril-induced in vitro lymphocyte transformation occurred in most patients with cutaneous reactions whereas in control patients captopril suppressed the in vitro lymphocyte proliferative response. Skin biopsies revealed histologic changes consistent with lymphocytic vasculitis. We conclude that epicutaneous skin tests with captopril are helpful in predicting the necessity of captopril withdrawal.

Adolescent↗
PubMed1984

Meta-[I-131]iodobenzylguanidine uptake in a nonsecreting paraganglioma.

In a patient with a paraganglioma at the carotid bifurcation, intense uptake of meta-[I-131]iodobenzylguanidine (I-131 MIBG) in the tumor was found. There was no clinical or biochemical evidence for catecholamine secretion by the tumor, although analysis of the tissue revealed that catecholamine biosynthesis took place. We conclude that accumulation of I-131 MIBG may occur in a paraganglioma, but does not necessarily indicate endocrine activity of the tumor.

3-Iodobenzylguanidine↗