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Biomedical subjects

F Boomsma

Publications and source records attributed to F Boomsma.

At least 127 records · Page 7Linked to original sources
PubMed1992

Catecholamines and regional hemodynamics during isovolemic hemodilution in anesthetized pigs.

The effects of stepwise isovolemic hemodilution on systemic and regional hemodynamics, oxygen flux, and circulating catecholamines were studied in six pigs anesthetized with midazolam and fentanyl. Reduction of the hematocrit from 28 to 9% resulted in doubling of the cardiac output, mainly due to an increase in stroke volume. Regional blood flows, measured using the radioactive microsphere technique, showed an increase in blood flow to all organs except liver (hepatic artery fraction) and adrenals, with a redistribution of cardiac output in favor of heart and brain (increase in blood flow 420 and 170%, respectively). Oxygen flux to most organs did not decrease until hematocrit decreased to 9%, while total body oxygen consumption was well maintained. Left ventricular oxygen consumption increased, but because left ventricular blood flow also increased, left ventricular extraction ratio did not increase. Circulating catecholamines did not play any role in these regulatory mechanisms.

Anesthesia↗
PubMed1992

Plasma prorenin as an early marker of microvascular disease in patients with diabetes mellitus.

To test the hypothesis that a high plasma prorenin can be used as an early marker of microvascular complications in patients with diabetes mellitus plasma prorenin was measured in 44 patients with urinary albumin excretion between 30 and 300 mg/24 h (microalbuminuria) and 120 patients with urinary albumin excretion below 30 mg/24 h (normoalbuminuria). A high plasma prorenin was associated with diabetic retinopathy, particularly the proliferative type, serum creatinine and the 24 h urinary albumin excretion rate. Plasma prorenin was not correlated with age, duration of diabetes, glycosylated hemoglobin, blood glucose, and blood pressure. The association between elevated plasma prorenin and retinopathy remained significant after adjustment for serum creatinine and albumin excretion. Independent of the presence or absence of microalbuminuria, the mean plasma level of prorenin was not above normal in patients without retinopathy and was 2 to 3 times normal in patients with proliferative retinopathy. Thus retinopathy appears to be an important determinant of abnormally high plasma prorenin. Angiotensin converting enzyme (ACE) was elevated in the patients with diabetes mellitus as compared to control subjects but the plasma levels of ACE in diabetics with normoalbuminuria was not significantly different from the group with microalbuminuria. Plasma prorenin was not associated with ACE. A plasma level of prorenin of 225 mU/L had a sensitivity of 0.84 and a specificity of 0.82 for detecting the presence of microalbuminuria.

Adult↗
PubMed1992

Partial escape of angiotensin converting enzyme (ACE) inhibition during prolonged ACE inhibitor treatment: does it exist and does it affect the antihypertensive response?

OBJECTIVE: To investigate whether the compensatory rise in renin and plasma angiotensin I in response to repeated angiotensin converting enzyme (ACE) inhibitor treatment results in a partial escape of ACE inhibition over a 24-h dosing interval. DESIGN: A single-blind placebo-controlled study in two parallel groups of eight hypertensive subjects receiving a once-daily dose of the ACE inhibitor, spirapril, of either 12.5 or 25 mg. Detailed 24-h studies were performed at the end of 2 weeks of placebo, and after the first dose and 2 weeks administration of spirapril. METHODS: Twenty-four-hour ambulatory blood pressure was measured invasively. True' angiotensins I and II were measured by radioimmunoassay after high-performance liquid chromatography separation. RESULTS: Both for the lower and higher doses of spirapril, the time-course of changes of spiraprilat, the active metabolite of spirapril, and ACE activity was similar but the maximal rise in angiotensin I was twofold higher after 2 weeks administration than after the first dose. Angiotensin II after the first dose of spirapril fell rapidly, with lowest values 2 to 4 h after dosing. At the end of dosing interval angiotensin II had returned to values seen under placebo with the 12.5-mg dose, but at the end of the 24-h period it was still suppressed with the 25-mg dose. Compared with these first-dose responses the initial maximal degree of angiotensin II suppression after 2 weeks administration of either dose was similar, but during the subsequent hours the degree of angiotensin II suppression tended to be less with the lower and was significantly less with the higher dose of spirapril. With the lower dose of spirapril responses of 24-h ambulatory blood pressure to the first dose and to 2 weeks of administration were almost superimposable, although blood pressures in the second half of the dosing interval tended to be higher during chronic treatment. With the higher dose the response of nocturnal blood pressure after 2 weeks administration was diminished by 8.8 mmHg systolic and 6.8 mmHg diastolic. CONCLUSIONS: Repeated ACE inhibitor treatment with once-daily spirapril leads to a partial escape of ACE inhibition, as reflected by a shorter duration of angiotensin II suppression. This escape also affects the antihypertensive response in the second half of the dosing interval.

Adult↗
PubMed1991

Improved measurement of urinary catecholamines by liquid-liquid extraction, derivatization and high-performance liquid chromatography with fluorimetric detection.

We report a sensitive and reliable assay for the determination of the urinary catecholamines norepinephrine, epinephrine and dopamine, based on selective extraction by a liquid-liquid extraction procedure, followed by selective derivatization with the fluorigenic agent 1,2-diphenylethylenediamine and quantification by high-performance liquid chromatography with fluorimetric detection. Comparison with a method using electrochemical detection shows that interference of an unknown compound, most probably N-methylepinephrine, which is an often-overlooked problem with methods using electrochemical detection and results in falsely high epinephrine concentrations, does not occur with the described fluorimetric method.

Catecholamines↗
PubMed1991

Dose-dependent effects of intravenous lorazepam on cardiovascular activity, plasma catecholamines and psychological function during rest and mental stress.

Dose-dependent effects of intravenously administered lorazepam on psychophysiological activity during rest and mental stress were studied in order to examine differential responses to doses which may induce anxiolysis or sedation. In a double-blind randomized cross-over study, nine male volunteers participated in a placebo and a lorazepam session, during which the subjects repeatedly performed a 10-min version of the Stroop Color Word Test (CWT), with 10 min of rest between the CWTs. Lorazepam was administered before each rest period in increasing doses of 0.0, 0.6, 0.13, 0.25 and 0.5 mg (total cumulative dose: 0.94 mg). Heart rate showed a dose-dependent decrease during rest with an ED50 of 0.13 mg lorazepam, while lorazepam had no effect on the cardiovascular and plasma catecholamine response magnitudes to the CWT. Subjective fatigue and reaction time increased significantly after 0.94 mg lorazepam, while at the same dose vigor decreased; state anxiety after the CWT was not influenced by lorazepam. These data show differential effects of lorazepam on cardiovascular, biochemical and psychological function. While heart rate was suppressed at low doses during rest and reaction time and subjective fatigue increased at doses which induced sedation, state anxiety and physiological response patterns to the CWT were not influenced by lorazepam.

Adult↗
PubMed1991

Differential release of amino acids, neuropeptides, and catecholamines from isolated nerve terminals.

We have investigated transmitter release from small and large dense-core vesicles in nerve terminals isolated from guinea pig hippocampus. Small vesicles are found in clusters near the active zone, and large dense-core vesicles are located at ectopic sites. The abilities of Ca2+ channel activation and uniform elevation of Ca2+ concentration (with ionophores) to evoke secretion of representative amino acids, catecholamines, and neuropeptides were compared. For a given increase in Ca2+ concentration, ionophore was less effective than Ca2+ channel activation in releasing amino acids, but not in releasing cholecystokinin-8. Titration of the average Ca2+ concentration showed that the Ca2+ affinity for cholecystokinin-8 secretion was higher than that for amino acids. Catecholamine release showed intermediate behavior. It is concluded that neuropeptide release is triggered by small elevations in the Ca2+ concentration in the bulk cytoplasm, whereas secretion of amino acids requires higher elevations, as produced in the vicinity of Ca2+ channels.

Amino Acids↗
PubMed1991

Blood pressure maintenance in hypertensive sympathectomized rats. I. Adrenal medullary catecholamines.

To assess the role of the sympathetic nervous system in the development of genetic hypertension, blood pressure (BP) was recorded in conscious adult Lyon hypertensive (LH) and normotensive (LN) rats that had received daily injections of saline or guanethidine at 1-13 wk of age. Guanethidine abolished the pressor response to tyramine, decreased plasma norepinephrine by greater than 70% and plasma 3,4-dihydroxyphenylglycol by approximately 90%, and did not change plasma epinephrine. Bilateral adrenalectomy further reduced plasma norepinephrine to 8 and 5% of control levels in LH and LN rats, respectively. BP was lowered (-7%) in sympathectomized rats, but the mean absolute BP difference between LH and LN rats was unaltered. Despite marked supersensitivity to alpha-adrenoreceptor stimulation, phentolamine induced only a small transient depressor response, which was abolished by adrenalectomy in sympathectomized rats. It is concluded that the sympathetic nervous system is not necessary for the development of hypertension in LH rats. After sympathectomy, circulating catecholamines, which mostly derive from the adrenal medulla, play only a minor role in BP maintenance.

Adrenal Medulla↗
PubMed1991

Not norepinephrine but its oxidation products bind specifically to plasma proteins.

Specific binding (up to 50%) of catecholamines to the plasma proteins albumin, transthyretin and alpha-1 acid glycoprotein has been reported repeatedly, but data are conflicting. In binding studies of tritiated norepinephrine (NE) to human serum albumin, we found specific binding to be an artifact, due to the presence of one or more oxidation products of NE which are rapidly formed at pH greater than 6.5. In the presence of large amounts of antioxidants NE is stable, and no specific binding occurs. The decrease in binding of tritiated NE with increasing amounts of nontritiated NE, previously thought to represent displacement, is actually the result of the inherent greater stability of NE at higher concentrations. A similar decrease in binding, this time representing real displacement, was obtained with increasing amounts of oxidation products, obtained by treating NE first with sodium hydroxide. Results with transthyretin, alpha-1 acid glycoprotein and with plasma were in full agreement with these conclusions. These observations emphasize the necessity for careful investigation of the purity and stability of the labeled ligand, not only in binding assays with catecholamines, but in binding assays in general. Our findings may also have bearings on the currently hotly pursued topic of catecholamine release in in vivo and in vitro experiments.

Blood Proteins↗
PubMed1991

[Origin and role of circulating catecholamines in the normotensive sympathectomized rat].

Early chronic treatment with guanethidine destroys peripheral sympathetic nerves while sparing the adrenal medulla, and does not lower blood pressure (BP) in conscious normotensive rats (Julien et al. Am J Physiol 1990; 259: H1337). Therefore, the origin and role of circulating catecholamines (CAs) in BP maintenance were examined in conscious normotensive control, sympathectomized (SNX)--daily s.c. injections of guanethidine from 1 to 13 weeks of age--and sympathectomized-adrenalectomized (SNX-A) rats by measuring i) their plasma CAs (norepinephrine, NE and epinephrine, E) and 3,4-dihydroxyphenylglycol (DHPG) by HPLC-FD, and ii) their mean BP (MBP) responses to phenylephrine and phentolamine (5 mg/kg i.v.). The doses of phenylephrine that produced similar MBP rises were 3 micrograms/kg in controls (44 +/- 4 mmHg) and 1.5 micrograms/kg in SNX (47 +/- 3 mmHg) and SNX-A (48 +/- 2 mmHg) rats. Results are as follows: [table: see text] In conclusion, in conscious normotensive SNX rats: (1) most of the circulating NE is of adrenomedullary origin and plasma DHPG derives from neuronal NE; (2) due to supersensitivity of the cardiovascular system, stimulation of alpha-adrenoreceptors by circulating CAs play a significant role in BP maintenance.

Adrenal Medulla↗
PubMed1990

Sleep patterns in congenital dopamine beta-hydroxylase deficiency.

Sleep patterns of two young female patients with congenital dopamine beta-hydroxylase deficiency are described. In this orthostatic syndrome central and peripheral noradrenergic failure occurs as a result of impaired beta-hydroxylation of dopamine. Consequently, the levels of dopamine and its metabolites are elevated. The relative importance of noradrenaline deficit in the face of dopamine excess for sleep-regulatory mechanisms can be inferred from the sleep pattern of these patients. No subjective sleep complaints were reported. The sleep patterns showed a high percentage of slow-wave sleep in both patients (29% and 34% of sleep period time) and a relatively low to normal percentage of REM sleep (18% and 21%). A normal cyclic REM sleep pattern was observed. Alpha-delta sleep occurred during light sleep (15% and 8%); consequently, the amount of stage 2 sleep was reduced. These results indicate that functional insufficiency of the noradrenergic system in two patients with dopamine beta-hydroxylase deficiency is not associated with profound changes in the (REM) sleep pattern. This supports a modulatory or permissive role for noradrenaline in REM sleep mechanisms.

Adult↗
PubMed1990

Epinephrine-induced enhancement of sympathetic activity in humans: inhibition by nonselective as well as beta 1-selective beta-adrenoceptor blockade.

To collect further evidence that epinephrine (EPI) facilitates norepinephrine (NE) release in humans, the effect of a low-dose intravenous (i.v.) infusion of EPI (20 ng kg-1/min) on arterial levels of NE and on local production of NE in the forearm was studied both before and during isometric exercise, cold provocation, head-up tilting, and mental stress in 10 subjects with borderline to mild hypertension. Studies were performed during placebo, during beta 1-selective beta-adrenoceptor blockade with atenolol, 50 mg once daily, and during nonselective beta-blockade with bopindolol, 1 mg once daily. Atenolol and bopindolol were administered for 1 week, 2 weeks apart, in a randomized double-blind cross-over design. During infusion of EPI, which increased plasma EPI levels to within the high physiologic range, resting levels of NE increased from 214 +/- 20 to 263 +/- 26 pg/ml (p less than 0.01) and resting NE forearm production increased from 296 +/- 48 to 529 +/- 98 pg 100 ml/min-1 (p less than 0.01). The enhancement of these two indices of sympathetic activity by EPI, observed during placebo, was abolished by bopindolol as well as by atenolol. The response of arterial NE, but not the response of forearm NE production, to three of the four stress tests was also enhanced (p less than 0.05) by EPI. This enhancement was also abolished by both beta-adrenoceptor antagonists. Our findings support the hypothesis that physiologic levels of EPI are capable of enhancing sympathetic activity in humans. This effect is mediated by beta-adrenoceptors and can be blocked not only by a nonselective but also by a beta 1-selective beta-adrenoceptor antagonist.

Adrenergic beta-Antagonists↗
PubMed1990

Haemodynamic and neurohumoral effects of xenon anaesthesia. A comparison with nitrous oxide.

Thirty-two patients were randomly allocated to be anaesthetised either with nitrous oxide or xenon. Those who received nitrous oxide required significantly more fentanyl peroperatively. Arterial blood pressure and heart rate were adequately controlled during surgery in both groups. Plasma noradrenaline and prolactin increased peroperatively in both groups, but plasma adrenaline and cortisol, which increased in the nitrous oxide group, did not change in the xenon group. Growth hormone was below control in those given xenon, but not in the nitrous oxide group, while dopamine remained unchanged in both groups. Postoperative plasma concentrations of noradrenaline, adrenaline, cortisol and prolactin (in both groups) and dopamine (in the nitrous oxide group) were elevated, and slowly returned to control. No differences were seen between the two gases in effects on plasma sodium and potassium. Xenon, because of its favourable haemodynamic, neurohumoral and antinociceptive properties, deserves a more prominent place in anaesthetic practice than it has so far occupied.

Adult↗
PubMed1990

Agonist-induced desensitization of beta-adrenoceptor function in humans. Subtype-selective reduction in beta 1- or beta 2-adrenoceptor-mediated physiological effects by xamoterol or procaterol.

We investigated the effects of beta 2- (procaterol 2 x 50 micrograms/day for 9 days) and beta 1- (xamoterol 2 x 200 mg/day for 14 days) adrenoceptor agonists on lymphocyte beta 2-adrenoceptor density and beta 1- and beta 2-adrenoceptor in vivo function (assessed as isoprenaline-infusion-evoked hemodynamic effects and exercise-induced tachycardia) in healthy volunteers. Procaterol decreased lymphocyte beta 2-adrenoceptor density and all beta 2-adrenoceptor-mediated in vivo effects but did not affect beta 1-adrenoceptor-mediated in vivo effects. In contrast, xamoterol neither affected lymphocyte beta 2-adrenoceptors nor beta 2-adrenoceptor-mediated in vivo effects but decreased beta 1-adrenoceptor-mediated in vivo effects. It is concluded that in humans, generally long-term application of beta 1- or beta 2-adrenoceptor agonists causes desensitization of beta-adrenoceptor function but in a beta-adrenoceptor subtype-selective fashion.

Adrenergic beta-Agonists↗
PubMed1989

Determination of catecholamines in human plasma by high-performance liquid chromatography: comparison between a new method with fluorescence detection and an established method with electrochemical detection.

We report a sensitive fluorimetric method, in which catecholamines are concentrated from plasma by liquid-liquid extraction and derivatized with the selective fluorescent agent 1,2-diphenylethyl-enediamine prior to chromatography. Optimal conditions for extraction, derivatization and chromatography were investigated. With alpha-methylnorepinephrine as internal standard, the chromatographic separations are complete within 6 min. Limits of detection are 0.3 pg for norepinephrine and epinephrine and 0.5 pg for dopamine. Coefficients of variation are low (3-7%). Comparison of plasma catecholamine values determined with this method and with an established method with electrochemical detection (n = 135) shows good correlation (r = 0.94-1.00), and regression lines are close to lines of identity.

Chromatography, High Pressure Liquid↗
PubMed1989

Induction of aromatic-L-amino acid decarboxylase by decarboxylase inhibitors in idiopathic parkinsonism.

We evaluated the effect of administration of L-dopa, alone or in combination with a peripheral decarboxylase inhibitor, on plasma levels of aromatic-L-amino acid decarboxylase (ALAAD). After single-dose administration of L-dopa plus benserazide (Madopar) in healthy subjects and in chronically treated patients with parkinsonism, plasma ALAAD followed for 2 to 3 hours fell, but returned to predosing levels within 90 minutes. Four groups of patients with idiopathic parkinsonism were studied during chronic treatment: Group I, no L-dopa treatment (n = 31); Group II, L-dopa alone (n = 15); Group III, L-dopa plus benserazide (n = 28); and Group IV, L-dopa plus carbidopa (Sinemet, n = 30). Plasma ALAAD 2 hours after dosing was normal in Groups I and II. ALAAD was increased threefold in Groups III and IV, suggesting induction of ALAAD by the coadministration of a peripheral decarboxylase inhibitor. In a study of 3 patients in whom L-dopa/benserazide was started, plasma ALAAD rose gradually over 3 to 4 weeks. Further detailed pharmacokinetic studies of L-dopa, dopamine, and ALAAD in plasma and cerebrospinal fluid are required to determine if the apparent ALAAD induction by a peripheral decarboxylase inhibitor may be related to the loss of clinical efficacy of combination therapy in some patients and how it is related to end-of-dose deterioration and on-off phenomena.

Aged↗
PubMed1989

Treatment of idiopathic parkinsonism with L-dopa in the absence and presence of decarboxylase inhibitors: effects on plasma levels of L-dopa, dopa decarboxylase, catecholamines and 3-O-methyl-dopa.

The effect of levodopa (L-dopa), alone or in combination with a peripheral decarboxylase inhibitor (PDI), on plasma levels of aromatic-L-amino acid decarboxylase (ALAAD, = dopa decarboxylase), L-dopa, 3-O-methyl-dopa (3-OMD), dopamine (DA), noradrenaline, adrenaline and dopamine beta-hydroxylase has been studied. In healthy subjects and in patients with parkinsonism plasma ALAAD level fell after administration of L-dopa + benserazide, but returned to previous levels within 90 min. In a cross-sectional study blood was obtained, 2 h after dosing, from 104 patients with idiopathic parkinsonism, divided into four groups: no L-dopa treatment (group 1), L-dopa alone (group 2), L-dopa + benserazide (Madopar) (group 3) and L-dopa + carbidopa (Sinemet) (group 4). Plasma ALAAD, which was normal in groups 1 and 2, was increased 3-fold in groups 3 and 4, indicating that there was induction of ALAAD by the co-administration of PDI. Despite this induction of ALAAD, in groups 3 and 4, with half the daily L-dopa dose compared with group 2, plasma L-dopa and 3-OMD levels were 5 times higher, while plasma DA levels were not different. The DA/L-dopa ratio was decreased 5-fold in group 2 and 16-fold in groups 3 and 4 as compared with group 1. Neither 3-OMD levels nor 3-OMD/L-dopa ratios correlated with the occurrence of on-off fluctuations. In a longitudinal study of three patients started on Madopar treatment the induction of plasma ALAAD was found to occur gradually over 3-4 weeks. Further detailed pharmacokinetic studies in plasma and cerebrospinal fluid are required in order to elucidate whether the ALAAD induction by PDI may be related to the loss of clinical efficacy of combination therapy in some patients and how it is related to end-of-dose deterioration and on-off phenomena.

Administration, Oral↗