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Biomedical subjects

P Smits

Publications and source records attributed to P Smits.

At least 145 records · Page 8Linked to original sources
PubMed1994

Quantification of Ca(2+)-ATPase in erythrocytes from subjects with essential hypertension or Raynaud's phenomenon.

The increased peripheral vascular resistance in subjects with essential hypertension and in subjects with primary Raynaud's phenomenon is thought to be the consequence of an impaired control of intracellular Ca2+ in vascular smooth muscle cells. Abnormal membrane handling of Ca2+ in human essential hypertension is not limited to vascular smooth muscle cells but has been demonstrated in a number of blood cells, for example, erythrocytes. Ca(2+)-ATPase activity and Ca(2+)-ATPase densities were measured in erythrocyte membranes from healthy volunteers and subjects with essential hypertension or with Raynaud's phenomenon. We found no significant differences between the three groups in the Ca(2+)-ATPase activity and in the number of Ca(2+)-ATPase immunoreactive sites per erythrocyte. Furthermore, we could not demonstrate any influence of sex or age on these two parameters. We conclude that, in essential hypertension and in Raynaud's phenomenon, the Ca2+ extrusion capacity of the erythrocytes is not altered.

Adult↗
PubMed1994

Vascular effects of pentoxifylline in humans.

In this study, we investigated the vasoactive effects of the alkylxanthine pentoxifylline and its interaction with the nucleoside adenosine in the forearm skeletal muscle vascular bed of 18 normotensive healthy volunteers. Pentoxifylline infusion into the brachial artery in dosages of 100, 300, and 1,000 micrograms/100 ml forearm volume (FAV)/min, induced increments of forearm blood flow (FBF) of 41 +/- 6, 125 +/- 22, and 295 +/- 57%, respectively (n = 12). Calculated forearm vascular resistance (FVR) showed a dose-dependent decrease during pentoxifylline infusion. Concomitant administration of caffeine (100 micrograms/100 ml/min), an adenosine antagonist, did not attenuate the vasodilator response to pentoxifylline (n = 6). Intraarterial (i.a.) infusion of adenosine alone (0.75, 1.5, 3.0, and 4.5 micrograms/100 ml/min) induced a dose-dependent forearm vasodilator response. Concomitant infusion of pentoxifylline (100 micrograms/100 ml/min) did not cause a convincing potentiation of the forearm vasodilator effect of adenosine. This study demonstrates that pentoxifylline induces vasodilation in human forearm skeletal muscle vascular bed of healthy young volunteers. This vasodilator response occurred at concentrations that are probably much higher than those achieved with oral treatment with pentoxifylline. Our data further suggest that pentoxifylline-induced vasodilation is not mediated by adenosine receptor stimulation, but may result from inhibition of the enzyme phosphodiesterase (PDE).

Adenosine↗
PubMed1994

Continuous infusion of furosemide in the treatment of patients with congestive heart failure and diuretic resistance.

OBJECTIVES: To assess the value of treatment with continuous intravenous infusion of furosemide (F) in patients with refractory congestive heart failure. DESIGN: Open uncontrolled dose-response study. SUBJECTS: Patients with congestive heart failure (those with New York Heart Association (NYHA) classes III and IV with an assessed amount of oedema of more than 5 kg and diuretic resistance were included [n = 10]). Diuretic resistance was defined as: failure to lose weight and/or inappropriate urinary sodium excretion (50 mmol 24 h-1) despite bed rest for a period of 2-3 days, salt and water restriction, orally and intravenously administered furosemide in a dose of 250 mg day-1, digoxin, and when possible an ACE inhibitor. Included patients were treated with continuous F infusion at a delivery rate of 20 mg-1 over 24 h. The infusion rate was gradually heightened up to a maximum dose of 160 mg h-1. MAIN OUTCOME MEASURES: Daily physical examination, history of side-effects, determination of serum electrolytes and 24-h electrolyte excretion during treatment with furosemide. RESULTS: Weight loss (mean +/- SD; 12.5 +/- 5 kg) and relief of symptoms was achieved in all patients. Mean (+/- SD) 24-h sodium output rose from 19 +/- 16 mmol 24 h-1 (n = 10) on oral therapy with 250 mg F to 137 +/- 85 mmol 24 h-1 (n = 8) during 80 mg h-1 and to 268 +/- 124 mmol 24 h-1 (n = 3) on the maximal dose of 160 mg h-1. CONCLUSION: Continuous infusion of F under careful monitoring of the patient is a safe, controllable and efficient treatment in patients with severe congestive heart failure and diuretic resistance.

Aged↗
PubMed1994

Characterization of ATP-induced vasodilation in the human forearm vascular bed.

BACKGROUND: Animal data indicate that ATP derived from aggregating thrombocytes or endothelium induces an endothelium-dependent vasodilator response that is mediated by P2y-purinergic receptors and is reduced when high dosages are administered. This reduced vasodilator response to high ATP doses has been associated with the concomitant release of endothelium-derived contracting factors. In contrast to the endothelium-dependent vasodilator response, ATP as released from sympathetic nerve endings induces a P2x-purinergic receptor-mediated vasoconstrictor response that may contribute to the attenuated vasodilator response to high dosages of luminally applied ATP. The dual action of ATP might be important in the pathophysiology of disease states characterized by an impaired endothelial function and increased thrombocyte aggregation. This study was performed to characterize the vascular response to ATP in humans. METHODS AND RESULTS: The brachial artery was cannulated in 50 healthy male volunteers (age, 18 to 44 years) for drug infusion and measurement of mean arterial pressure. Forearm blood flow was recorded by venous occlusion strain-gauge plethysmography. ATP induced a dose-dependent vasodilator response that was significantly higher than the effect of equimolar adenosine infusion and that was not reduced by concomitant infusion of the P1-purinergic receptor antagonist theophylline. The infusion of the NO synthase antagonist NG-monomethyl-L-arginine (L-NMMA) reduced the average fall in forearm vascular resistance (FVR) to acetylcholine (-59 +/- 6% [mean +/- SEM] versus -42 +/- 8%; P < .05; N = 10) but did not affect the vasodilator response to ATP (-68 +/- 3% versus -64 +/- 6%; P > .1; N = 10) or sodium nitroprusside (SNP; -53 +/- 3% versus -49 +/- 4%; P > .01; N = 6). The L-NMMA-induced increase in FVR appeared to be related to the type of vasodilator pretreatment, being 94.7 +/- 16.7%, 44.9 +/- 8.7%, and 40.8 +/- 7.3% for acetylcholine, ATP, and SNP pretreatment, respectively (P < .01 for acetylcholine versus ATP and SNP; P > .1 for ATP versus SNP). In contrast to animal data, high dosages of intra-arterially infused ATP (up to 1000 micrograms.100 mL forearm-1.min-1) did not reveal a reduction in the forearm vasodilator response but appeared to be similar to the maximal forearm vasodilation as observed during postocclusive reactive hyperemia. CONCLUSIONS: These observations indicate that ATP induces a potent dose-dependent vasodilator response that is not mediated by P1-purinergic receptor stimulation or by the release of nitric oxide. Moreover, in healthy volunteers, the vasodilator response to high intra-arterial dosages of ATP is not reduced by the release of endothelium-derived contracting factors or by the stimulation of P2x-purinergic receptors on the smooth muscle cells.

Adenosine Triphosphate↗
PubMed1994

Endothelium and the regulation of vascular tone with emphasis on the role of nitric oxide. Physiology, pathophysiology and clinical implications.

After the discovery by Furchgott and colleagues in 1980 that the endothelium plays an obligatory role in acetylcholine-induced vasodilation many investigators have elucidated the role of the endothelium in the regulation of vascular tone. While the sympathetic nervous system serves the organism as a whole, the endothelium appears to act as a local regulator adapting blood flow to local metabolic needs. A variety of endothelium-derived relaxing and contracting factors such as nitric oxide, prostacyclin, endothelium-derived hyperpolarizing factor, endothelin and thromboxane A2 play a role in the endothelium-dependent control of vascular tone. Furthermore, nitric oxide inhibits thrombocyte aggregation and adhesion. Many diseases have been reported to be associated with an impaired endothelium-dependent vasodilation which may contribute to an increased susceptibility to vasospasm, decreased inhibition of thrombus formation and an impaired ability to reduce vascular resistance in ischaemic conditions. In hypertension, hypercholesterolaemia and diabetes mellitus this impairment may be interpreted as an early marker of a process that ultimately will lead to atherosclerosis. The impaired endothelium-dependent vasodilation probably contributes to the increased peripheral vascular resistance in hypertension and heart failure. The role of the endothelium does not seem to be restricted to cardiovascular diseases. Several mediators of inflammation stimulate the endothelium to release nitric oxide, suggesting an important role of the endothelium in the haemodynamic sequelae of sepsis.

Cardiovascular Diseases↗
PubMed1994

Comparison of clinical examination, current and vibratory perception threshold in diabetic polyneuropathy.

The study of diabetic polyneuropathy is complicated by a lack of clear definitions and the absence of a simple reliable test procedure. Recently, a new sensory perception testing device has been introduced for detection of thresholds for electrical stimuli (current perception: CPT) at different frequencies (Neurometer). We compared standardized clinical examination scores with measurements of vibratory perception threshold (VPT) and CPT (foot) and obtained reproducibility figures. Participants in the study were healthy controls (H, n = 33), diabetic patients without clinical signs of neuropathy (DN-, n = 23), diabetics with overt diabetic neuropathy (DN+, n = 22), and patients with a diabetes duration of over 20 years (D20, n = 38). As expected, there were highly significant differences (Wilcoxon) in CPT, VPT and neurological scores between H/DN- and DN+ (p < 0.001), but not between H and DN-. Correlation between CPT and total as well as partial (reflecting small and large fibre functions) neurological examination score were highest at 2000 Hz (r = 0.88); no advantage of lower frequency CPT could be identified. CPT seemed rather insensitive in detecting neuropathy. Correlations between CPT and VPT were only moderate and maximal at 2000 Hz (r = 0.61). Reproducibility of CPT was good at 2000 Hz (coefficient of variation 13.3-20.2%), but moderate to poor at lower frequencies (ranging to 62%). We conclude that CPT and VPT quantitative sensory testing is only of limited value, mainly because of high variability and poor reproducibility.

Adult↗
PubMed1993

The cardiovascular interaction between caffeine and nicotine in humans.

In a placebo-controlled, double-blind randomized design, we investigated the cardiovascular interaction between caffeine (250 mg intravenously) and nicotine (4 mg chewing gum) in 10 healthy volunteers, both under baseline conditions and during physical and mental stress (standing up and mental arithmetic). Caffeine alone induced a significant increase in blood pressure associated with a decrease in heart rate, whereas nicotine alone increased both blood pressure and heart rate. The combination of caffeine and nicotine increased systolic and diastolic blood pressure by 10.8 +/- 2.0 and 12.4 +/- 1.9 mm Hg, respectively. This pressor response did not differ significantly from the calculated additive effects of caffeine and nicotine on blood pressure, measuring 12.9 +/- 2.0 and 14.2 +/- 2.1 mm Hg, respectively. Heart rate and forearm blood flow also showed a similar response when the combination of caffeine and nicotine was compared with the calculated sum. During physical stress (standing up), blood pressure, heart rate, and plasma catecholamines increased in the placebo test. The pressor response to standing up was less pronounced after the combination of caffeine and nicotine compared with the sum of the separate effects (combination versus sum: delta diastolic blood pressure, 24.7 +/- 1.9 versus 35.2 +/- 2.6 mm Hg [p < 0.01]; delta mean arterial pressure, 22.1 +/- 2.0 mm Hg versus 28.6 +/- 1.6 mm Hg [p < 0.05]). The plasma catecholamine response did not differ between the combination and the sum of both drugs. During mental arithmetic, blood pressure, heart rate, and forearm blood flow increased in the placebo test. The forearm vasodilator response to mental stress was attenuated by the combination of caffeine and nicotine compared with the sum of both drugs (combination versus sum: delta forearm blood flow, -0.1 +/- 0.3 versus 1.4 +/- 0.5 ml/100 ml/min [p < 0.05]). We conclude that the combined administration of caffeine and nicotine shows additive effects on cardiovascular parameters during baseline conditions but less than additive effects during sympathoadrenal stimulation.

Adult↗
PubMed1993

Effect of chronic smoking on endothelium-dependent vascular relaxation in humans.

1. Cigarette smoking is one of the major risk factors for the development of atherosclerosis. It is not clear, however, whether chronic cigarette smoking impairs the normal physiological function of the endothelium before the development of morphological vascular lesions. To test this, we investigated endothelium-dependent vascular relaxation in young habitual smoking subjects. 2. In 11 non-smokers and 10 habitual smokers we measured the changes in bilateral forearm blood flow, arterial blood pressure and forearm vascular resistance (ratio between mean arterial blood pressure and forearm blood flow) during three interventions: post-occlusive forearm hyperaemia, intrabrachial infusion of methacholine which causes vasodilatation by stimulating the release of endothelium-dependent relaxing factor, and intrabrachial infusion of sodium nitroprusside which causes vasodilatation independently from the endothelium by a direct effect on the vascular smooth muscle wall. 3. During infusion of the highest dose of methacholine, forearm vascular resistance decreased by 91.7 +/- 1.4% in the smokers and by 89.9 +/- 1.8% in the non-smokers. During infusion of sodium nitroprusside, forearm vascular resistance decreased by 80.0 +/- 3.8% in the smokers as compared with 80.7 +/- 6.1% in the non-smokers. There was no difference in basal forearm vascular resistance or in post-ischaemic reactive hyperaemia between smokers and non-smokers. Thus, vasodilatation induced by both methacholine and sodium nitroprusside was not significantly different between smokers and non-smokers. 4. We conclude that in young habitual cigarette smokers the endothelium-dependent vasodilation in the forearm seems to be preserved, suggesting that habitual smoking does not result in permanent endothelial dysfunction in the human forearm.

Adult↗
PubMed1993

NG-monomethyl-L-ARG reduces the forearm vasodilator response to acetylcholine but not to methacholine in humans.

We compared the contribution of nitric oxide (NO) in methacholine (MCh)- and acetylcholine (ACh)-induced vasodilation using the NO-synthase inhibitor NG-monomethyl-L-arginine acetate (L-NMMA-acetate) in two groups (A and B) of 6 healthy male volunteers. The left brachial artery was cannulated for drug infusion and recording of mean arterial pressure (MAP). Forearm blood flow (FBF) was measured on both sides by venous occlusion mercury-in-silastic strain-gauge plethysmography. All measurements were performed with occluded hand circulation. Forearm vasodilator response to three increasing dosages of MCh (0.03, 0.3, and 1 micrograms/100 ml forearm/min; group A) or ACh (0.5, 2, and 8 micrograms/100 ml forearm/min; group B) was studied first. Forty-five minutes later, these infusions were repeated (after and during local administration of L-NMMA). L-NMMA-acetate infusion alone increased basal forearm vascular resistance (FVR, mean +/- SE) by 86.2 +/- 14.5 and 99.5 +/- 27.4% in groups A and B, respectively (p < 0.05) without significant FVR changes in the control arm. MCh-induced vasodilation was not attenuated by concomitant L-NMMA-acetate infusion. In contrast, L-NMMA-acetate significantly reduced the averaged percentage decrease in FVR during infusion of ACh from 55.7 +/- 9.1 to 35.4 +/- 11.8% (p < 0.05). L-NMMA-acetate increased basal vascular tone and reduced the vasodilator response to ACh. MCh induced vasodilation to a degree similar to that obtained with ACh. Nevertheless, MCh-induced vasodilation could not be attenuated by L-NMMA, suggesting that NO contributes differentially to methacholine- and ACh-induced vasodilation in humans.

Acetylcholine↗
PubMed1993

Endothelium-dependent vascular relaxation in patients with type I diabetes.

The endothelium plays an important role in the regulation of vascular tone. Although animal data show evidence for an impaired endothelium-dependent vasodilation in diabetes, human in vivo data are scarce. We investigated 11 type I diabetic patients and 11 matched healthy control subjects. The diabetic patients were selected on their relatively poor metabolic regulation (HbA1c > 8.5%), but none showed signs of microvascular complications. In all subjects, we recorded the forearm vasodilator responses to three different stimuli: 1) 5 min of forearm ischemia to obtain a maximal vasodilator response; 2) infusion of MCh into the brachial artery (dosages: 0.03-0.3-1.0 micrograms.min-1.100 ml-1 forearm volume) to evaluate endothelium-dependent vasodilation; and 3) intra-arterial infusion of SNP (dosages: 0.06-0.2-0.6 micrograms.min-1.100 ml-1) to evaluate endothelium-independent vasodilation. The diabetic patients had their usual subcutaneous insulin dose and breakfast 90 min before the start of the test. Baseline levels of BP and FBF were similar in both groups. The PORH response was similar in both groups, with a percentage fall in FVR of 92 +/- 1% in diabetic patients and 94 +/- 1% in control subjects. In the control subjects, MCh infusions exerted a dose-dependent vasodilator response with a maximal fall in the FVR of 90 +/- 2%. The highest dose of SNP induced a fall in FVR of 81 +/- 6% in this group. In diabetic patients, the percentage decrements in FVR during the several dosages of MCh and SNP were similar when compared with the control group. We conclude that chronic hyperglycemia, as occurred in our patients with uncomplicated diabetes mellitus, does not impair endothelium-dependent vasodilation in vivo.

Adult↗
PubMed1993

Impaired vasodilator response to atrial natriuretic factor in IDDM.

Diabetes mellitus has been associated with both elevated plasma concentrations of the natriuretic and vasorelaxant hormone atrial natriuretic factor and with a reduced natriuretic response to this hormone. We now hypothesize that the vasodilator response to atrial natriuretic factor is attenuated in IDDM. Forearm vasodilator responses to the infusion of six increasing dosages of atrial natriuretic factor into the brachial artery were registered by venous occlusion strain gauge plethysmography in 10 patients with uncomplicated IDDM and in 10 age-, sex-, and weight-matched control subjects. Baseline levels of blood pressure, forearm blood flow, and plasma concentrations of atrial natriuretic factor were not different between control subjects and patients with diabetes. In control subjects, atrial natriuretic factor induced a percentage fall in the forearm vascular resistance of -29 +/- 5% at the lowest to -72 +/- 4% at the highest infusion rate. In patients with diabetes this fall was significantly attenuated, measuring -2 +/- 7 and -45 +/- 4%, respectively, (P < 0.001 vs. control subjects). During infusion of atrial natriuretic factor into the brachial artery, the calculated regional production of cGMP (second messenger of atrial natriuretic factor) increased from 1.2 +/- 1.1 to 22.8 +/- 4.8 pmol.min-1 x 100 ml-1 in the control subjects, whereas hardly any change occurred in the patients with diabetes (from -2.1 +/- 1.2 to 2.9 +/- 4.7 pmol.min-1 x 100 ml-1). Furthermore, both control and diabetic subjects demonstrated an equal forearm vasodilator response to increasing infusion rates of the control vasodilator sodium nitroprusside. We conclude that uncomplicated IDDM is associated with a specific reduction in the vascular responsiveness to atrial natriuretic factor.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

The effect of fluoxetine on body weight, body composition and visceral fat accumulation.

In this study the effect of fluoxetine versus placebo treatment on body weight, body composition and abdominal fat areas, assessed from three magnetic resonance imaging scans at umbilicus level, was investigated. Thirty-eight abdominal overweight men aged 41 +/- 7 years (mean +/- s.d.), BMI 27.9 +/- 1.2 kg/m2 and WHR 0.97 +/- 0.03 were given dietary advice and a placebo (n = 20) or fluoxetine treatment (n = 18, 60 mg/day) for 12 weeks after a placebo run-in of two weeks. Measurements were carried out during run-in and at week 12 of treatment. The treatment groups did not differ at the start of the study. After treatment, weight loss (on average) was observed in both groups: -2.4 +/- 0.6 kg and -5.9 +/- 0.7 kg for the placebo and fluoxetine groups, respectively. Weight loss was significantly larger in the fluoxetine group (P = 0.0004). The reduction of fat mass tended to be larger (P = 0.08), and the reduction of fat-free mass was considerably larger in the fluoxetine group (P = 0.0005). Absolute (and proportional) changes in visceral and subcutaneous fat areas (cm2) were +2 +/- 26 (+1%) and -9 +/- 26 (-4%) in the placebo group, and -9 +/- 30 (-3%) and -30 +/- 27 (-13%) in the fluoxetine group. In both groups the proportional change in subcutaneous fat area was larger than the change in visceral fat (P < 0.02). Only in the fluoxetine group was the decrease in subcutaneous fat area significant, and larger compared to the placebo group (P = 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Abdomen↗
PubMed1992

Diuretic efficiency of furosemide during continuous administration versus bolus injection in healthy volunteers.

Furosemide delivery rate in the nephron has been reported to be one of the major determinants of diuretic response. In a randomized, crossover double-blind study in eight healthy volunteers, we tested this hypothesis by comparing continuous intravenous infusion of furosemide (infusion rate, 4 mg/hr) during 8 hours after administration of an intravenous loading dose of 8 mg (total dose, 40 mg) with an intravenous bolus injection of 40 mg furosemide. During the study days subjects were rehydrated with isovolumetric amounts of fluid. Mean total urinary volume (Vur), sodium (UNa), potassium, and chloride excretion after 8 and 24 hours were significantly greater after treatment with continuous furosemide infusion when compared with bolus injection, whereas total urinary furosemide excretion showed no differences (Vur bolus versus Vur infusion, 5270 versus 6770 ml/8 hours; UNa bolus versus UNa infusion, 314 versus 430 mmol/8 hours; both p less than 0.001). These findings strongly support the concept of the furosemide delivery rate into the nephron as a determinant of diuretic efficiency.

Adult↗
PubMed1992

Absorption of high dose furosemide (frusemide) in congestive heart failure.

To investigate the influence of the presence of oedema on the pharmacokinetics and pharmacodynamics of furosemide (frusemide) we selected 9 hospitalised patients (mean age 70.3 years, range 59 to 84 years) with severe congestive heart failure (NYHA III to IV) and an assessed amount of peripheral oedema of at least 5 kg. In these patients the absorption of a single oral dose of furosemide 250 mg was studied when their heart failure was decompensated and again, after intensive therapy, when it was clinically compensated. The mean (+/- SEM) weight loss after clinical treatment was 12.0 +/- 2.2 kg. Individual furosemide plasma concentration-time curves could be fitted adequately to a 1-compartment model with 1 first-order absorption and elimination process, in which absorption took place in 2 parts with different lag times. Comparing the decompensated state with the compensated state we did not find significant differences in pharmacodynamics, absorption half-life, elimination half-life, time to peak serum concentration, peak serum concentration itself and area under the plasma concentration-time curve. However, the relative amount of furosemide absorbed in the first fraction was significantly increased after compensation. We conclude that the presence of massive oedema in patients with congestive heart failure has a minor influence on the pharmacokinetics and pharmacodynamics of high dose oral furosemide.

Administration, Oral↗