Search PubMed⌕ Search

Biomedical subjects

P Smits

Publications and source records attributed to P Smits.

At least 163 records · Page 9Linked to original sources
PubMed1991

Dose-dependent inhibition of the hemodynamic response to dipyridamole by caffeine.

We investigated the effects of the adenosine antagonist caffeine on the hemodynamic response to dipyridamole infusion (0.4 mg/kg for 4 minutes). According to a randomized, placebo-controlled double-blind protocol, eight normotensive volunteers each participated in five tests: placebo after placebo, dipyridamole after placebo, and dipyridamole after 1, 2, and 4 mg/kg caffeine. Infusion of caffeine alone (4 mg/kg) induced an increase in mean arterial pressure of 6.1 +/- 0.5 mm Hg versus 1.5 +/- 0.9 mm Hg after placebo (p less than 0.05). Infusion of dipyridamole alone exerted a characteristic hemodynamic response with an increase in systolic blood pressure (+8.4 +/- 2.4 mm Hg), pulse pressure (+7.0 +/- 2.4 mm Hg), heart rate (+25.7 +/- 3.8 beats/min) and calculated rate-pressure product (+3419 mm Hg x beats per minute), all being significantly different from the changes induced by placebo. Caffeine induced a dose-dependent attenuation of the response to dipyridamole, with a significant negative correlation between the dose of caffeine on the one hand (0, 1, 2, and 4 mg/kg) and the dipyridamole-induced increments in systolic blood pressure (r = -0.53), pulse pressure (r = -0.50), heart rate (r = -0.95), and rate-pressure product (r = -0.93) on the other hand. We conclude that caffeine attenuates the hemodynamic response to dipyridamole infusion in humans in a dose-dependent fashion. Because of the wide-spread use of caffeine, this pharmacologic interaction may be of clinical importance, for example, in the diagnostic use of dipyridamole in thallium-201 myocardial imaging.

Adult↗
PubMed1991

Role of the wrist cuff in forearm plethysmography.

1. To determine whether a wrist cuff is necessary to measure the forearm blood flow correctly, we studied the effects of wrist cuff inflation to supra-venous and supra-systolic pressure values over a large range of forearm blood flow values: in the basal state, during post-occlusive hyperaemia of the hand, and during heating of the hand with warm air. Eleven healthy men participated, and the study was carried out at two different ambient temperatures of 20 and 25 degrees C. 2. In the basal state, the measured forearm blood flow was lowest with the wrist cuff at supra-systolic pressure. With the wrist cuff at supra-venous pressure the forearm blood flow was also lower than with an uninflated cuff, but only significantly so when the basal forearm blood flow was higher (at a room temperature of 25 degrees C). 3. During post-occlusive hyperaemia, inflating the wrist cuff to supra-systolic pressure produced the lowest forearm blood flow value at both room temperatures. In addition, with the wrist cuff at supra-venous pressure, forearm blood flow values were lower than with the uninflated cuff, but the supra-venous cuff pressure was clearly less efficient in excluding the hand blood flow than the supra-systolic cuff pressure. 4. During heating of the hand, both supra-systolic and supra-venous cuff pressures were effective in excluding the hand blood flow at both room temperatures. The forearm blood flow measured with the wrist cuff at supra-systolic pressure was lower than that measured with the wrist cuff at supra-venous pressure, but the difference was only significant at a room temperature of 20 degrees C. 5. In conclusion, we have demonstrated that a wrist cuff at supra-systolic pressure is most appropriate for the exclusion of the hand circulation in order to measure the forearm blood flow correctly.

Forearm↗
PubMed1991

The effect of caffeine on renal vein renin concentration in patients with renal arterial disease.

The aim of this study was to investigate whether caffeine stimulates selectively renal vein renin levels at the side of unilateral stenosis in patients with renovascular hypertension. In this study seven of the involved patients had renal arterial stenosis and four had no stenosis. Four of the seven patients with a stenosis had retrospectively-proven renovascular hypertension. Renal vein renin sampling was performed before and after intravenous administration of caffeine. Caffeine did not induce any consistent effect on plasma renin activity in the renal veins, either on the stenotic side or on the contralateral side in patients with renovascular hypertension. There were no consistent caffeine mediated changes in systemic plasma renin activity.

Caffeine↗
PubMed1991

Adenosine attenuates the vasoconstrictor response to the cold pressor test in humans.

The forearm vasoconstrictor response to a standardized cold pressor test (CPT) was studied twice in eight healthy subjects, once during local intraarterial infusion of adenosine and once during infusion of equipotent dosages of the control vasodilator sodium nitroprusside (SNP). During local SNP infusion, the forearm vascular resistance (FVR) decreased from 70 +/- 14 to 30 +/- 7 arbitrary units (AU). Adenosine induced a comparable vasodilator response, with a decrease in FVR from 56 +/- 14 to 28 +/- 6 AU. Subsequent cold exposure induced a mean percentage increase in FVR of 62 +/- 17% during SNP, whereas the increase was only 27 +/- 12% during adenosine infusion (p = 0.014). There were no differences in the calculated cold-induced changes in forearm production of norepinephrine (NE) between the SNP and the adenosine tests. We conclude that adenosine attenuates forearm vasoconstrictor response to the CPT, probably by a postjunctional mechanism of action.

Adenosine↗
PubMed1991

Adenosine attenuates the response to sympathetic stimuli in humans.

The effect of adenosine on the forearm vasoconstrictor response to alpha-adrenergic and sympathetic stimulation was studied in healthy volunteers. During a predilated state achieved by infusion of sodium nitroprusside into the branchial artery, subsequent infusion of norepinephrine induced a mean increase in forearm vascular resistance of 571%, whereas this response was only 270% when an equipotent vasodilator dose of adenosine was used instead of sodium nitroprusside (nitroprusside versus adenosine, p less than 0.05, n = 6). A comparable difference was found when the endogenous release of norepinephrine was stimulated by the local infusion of tyramine, with tyramine-induced increments in forearm vascular resistance of 438% during nitroprusside versus 93% during adenosine (n = 6, p less than 0.05). During these tyramine infusions a similar increase in the calculated forearm norepinephrine overflow occurred in the adenosine and the nitroprusside tests. In a third experiment, we demonstrated that adenosine also reduced the vasoconstrictor response to lower body negative pressure, an endogenous stimulus, of the sympathetic nervous system. During nitroprusside, lower body negative pressure induced an increase in forearm vascular resistance of 135%, whereas this was 39% during adenosine (n = 6, p less than 0.05). We conclude that adenosine attenuates the response to sympathetic nervous system-mediated vasoconstriction in humans, and that this effect may at least partly be explained by a postsynaptic inhibition of alpha-adrenergic vasoconstriction. Therefore, we think that adenosine may be an important endogenous modulator of sympathetic nervous system activity in humans.

Adenosine↗
PubMed1991

Boiled coffee and blood pressure. A 14-week controlled trial.

The question of whether long-term elimination of coffee from the diet lowers blood pressure has not been settled. Consumption of Scandinavian-style "boiled coffee" is associated with coronary heart disease. However, little is known about the effect of brewing method on the blood pressure-raising potential of coffee. We have studied the effects on blood pressure and heart rate of total elimination of coffee and tea in comparison with drinking boiled coffee consumed as such, or boiled coffee consumed after filtration through paper filter. Thirty-one women and 33 men first consumed 6 cups/day of boiled and filtered coffee for 17 days. Then they were randomly divided into three groups, which for the next 79 days received either unfiltered boiled coffee (caffeine content 860 mg/l), boiled-and-filtered coffee (887 mg caffeine/l), or no coffee, the latter being replaced by fruit juice and mineral water. Total elimination of coffee did not significantly affect blood pressure or heart rate relative to boiled-and-filtered coffee. In subjects who drank boiled coffee, mean ambulant systolic blood pressure rose significantly relative to those who consumed boiled-and-filtered coffee (mean difference +/- SEM, 3.1 +/- 1.1 mm Hg, p = 0.006). This response showed a tendency to be stronger for women (4.5 +/- 1.8 mm Hg) than for men (1.7 +/- 1.2 mm Hg). We conclude that elimination of filtered coffee has no substantial long-term effect on blood pressure, but consumption of unfiltered boiled coffee may cause a slight but significant rise in systolic blood pressure.

Adult↗
PubMed1991

Attenuated forearm vasodilator response to atrial natriuretic factor in the elderly.

The vasodilator potency of human atrial natriuretic factor-(99-126) was investigated in the forearm vascular bed of 10 young and 10 elderly normotensive volunteers with venous occlusion strain gauge plethysmography. Atrial natriuretic factor was infused at six increasing dose steps into the brachial artery from 0.001 up to 0.3 microgram/min/100 ml of forearm volume. This induced a mean +/- SEM increase in blood flow from 1.4 +/- 0.2 up to 6.0 +/- 1.0 ml/min/100 ml in the young and from 1.4 +/- 0.2 up to 3.9 +/- 0.6 ml/min/100 ml in the elderly. The dose-response curves of forearm blood flow and of forearm vascular resistance after increasing infusion rates of atrial natriuretic factor were shifted to the right in the elderly when compared with the young subjects. The mean percent decrease in forearm vascular resistance, induced by atrial natriuretic factor, during this dose-response curve averaged -31 +/- 3% in the elderly versus -56 +/- 3% in the young subjects (p = 0.0002). The calculated forearm spillover of the second messenger of atrial natriuretic factor, cyclic guanosine monophosphate, significantly increased from baseline values of 1.2 +/- 1.1 and 0.7 +/- 0.5 pmol/min/100 ml in young and elderly subjects, respectively, up to 23.2 +/- 5.0 and 30.5 +/- 7.0 pmol/min/100 ml during the highest dose of atrial natriuretic factor (both p less than 0.01 versus baseline). There were no significant differences in the increments of the forearm spillover of this second messenger between both age groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

False-negative dipyridamole-thallium-201 myocardial imaging after caffeine infusion.

The vasodilator effect of intravenously administered dipyridamole may be caused by an increase in endogenous plasma adenosine levels. We evaluated the effect of caffeine, an adenosine receptor antagonist, on the diagnostic results of dipyridamole-201Tl myocardial imaging in eight patients with coronary artery disease. Caffeine infusion significantly attenuated the dipyridamole-induced fall in blood pressure and the accompanied increase in heart rate. The infusion of dipyridamole alone resulted in chest pain and ST-segment depressions on the electrocardiogram in four patients, whereas none of these problems occurred when the tests were repeated after caffeine. In six of eight patients, caffeine was responsible for false-negative dipyridamole-201Tl tests. Semiquantitive scores of the dipyridamole-induced 201Tl perfusion defects were decreased by caffeine from 9.0 +/- 0.9 to 2.0 +/- 1.1 points (p less than 0.05). Computerized analysis revealed a caffeine-mediated reduction in the percent reversibility of the images from 46% +/- 16% to 6% +/- 10% (p less than 0.05). We conclude that the use of caffeinated products prior to dipyridamole-201Tl testing may be responsible for false-negative findings.

Caffeine↗
PubMed1990

Comparison of the diuretic effect and absorption of a single dose of furosemide and free and the fixed combinations of furosemide and triamterene in healthy male adults.

The absorption and diuretic effect of furosemide 40 mg alone (F), and of the free (F + T) and the fixed (FT) combinations of furosemide 40 mg and triamterene 50 mg have been compared in 12 healthy young men. A slight reduction in the area under the concentration-time curve (AUC) of plasma furosemide was found for the fixed combination (AUC480) F2.58 micrograms.h.ml-1; F + T 2.46 micrograms.h.ml-1; FT 1.97 micrograms.h.ml-1. There was a significant reduction in the AUC480 of plasma triamterene (F + T 204.9 micrograms.h.l-1; FT 130.2 micrograms.h.l-1). Sodium excretion after F + T and FT was more pronounced than after F (F + T 302 mmol; FT 311 mmol; F259 mmol). When compared to F alone, there was a reduction in the 24-hour potassium excretion after F + T as well as after FT (F 121 mmol; F + T 104 mmol; FT 107 mmol). It is concluded that the absorption of triamterene was significantly reduced after ingestion of the fixed combination tablet. However, in healthy male adults this had no influence on its natriuretic and potassium-sparing effect as compared to the free combination.

Absorption↗
PubMed1990

Hemodynamic effects of atrial natriuretic factor in young and elderly subjects.

Because levels of plasma atrial natriuretic factor (ANF) increase with advancing age, a diminished hemodynamic responsiveness to ANF in the elderly has been hypothesized in the literature. Therefore hemodynamic effects after two infusion rates (0.25 and 2.0 micrograms/min) of atrial natriuretic factor (99-126) were investigated in young (n = 8) and elderly (n = 9) volunteers in a double-blind, randomized, and placebo-controlled protocol. After low-rate infusion, ANF concentrations increased to the upper normal range, and only minor effects were observed. In contrast, high-rate infusion resulted in a decrease in blood pressure and forearm vascular resistance, whereas an increase in heart rate was observed in both groups. Between young and elderly subjects, a significant difference was observed in the ANF-induced decrease in systolic blood pressure (mean +/- SD, -4% +/- 4% versus -12% +/- 7%, p less than 0.05) and mean arterial pressure (-6% +/- 5% versus -11% +/- 4%, p less than 0.05) during the high rate infusion. When compared with the concentrations of the young subjects, the ANF concentrations reached at both ANF dosages were higher in the elderly subjects; this was the result of a diminished ANF clearance in the elderly subjects. After correction of the changes of systolic blood pressure and mean arterial pressure for the higher ANF levels reached within this elderly group, no difference between young and elderly subjects remained. We conclude that a diminished cardiovascular responsiveness to ANF with advancing age could not be demonstrated. In contrast, the high-rate infusion of ANF induced an increased hemodynamic response in the elderly subjects, but this seems to be the result of the higher ANF levels reached within this group.

Adult↗
PubMed1990

Caffeine and theophylline attenuate adenosine-induced vasodilation in humans.

In this study the local vasoactive effects of adenosine were explored in the human forearm. Adenosine (15 micrograms/100 ml forearm/min) infused into the brachial artery (n = 6) increased forearm blood flow by 572% +/- 140%, versus - 0.5% +/- 5.8% during placebo infusion (p less than 0.01). Lower adenosine infusion rates (5 micrograms/100 ml forearm/min, three times) induced forearm blood flow increments to 330% +/- 94%, 339% +/- 67% and 330% +/- 79%, respectively (n = 8). These forearm blood flow responses were reduced (p = 0.02) during concomitant intra-arterial infusion of two doses of caffeine (30 and 90 micrograms/100 ml forearm/min) to 150% +/- 45% and 98% +/- 28%, respectively. Theophylline (30 micrograms/100 ml forearm/min; n = 6) also significantly attenuated the adenosine-induced increase in forearm blood flow. Enprofylline (30 micrograms/100 ml forearm/min), a related xanthine with a low affinity to adenosine receptors in vitro, did not change the response to adenosine. Nonspecific vasodilation by sodium nitroprusside infusion (50 ng/100 ml forearm/min) was not inhibited by caffeine compared with placebo (forearm blood flow responses were 202% +/- 21% versus 216% +/- 40%; n = 6). This study demonstrated that caffeine and theophylline specifically reduce adenosine-induced vasodilation in humans, supporting the existence of functional human vascular adenosine receptors.

Adenosine↗
PubMed1990

Absence of magnesium sparing effect of a single dose of triamterene in combination with frusemide in healthy male adults.

In a study of cross-over randomized design in 12 healthy volunteers we compared the effect on magnesium excretion after administration of single oral doses of frusemide 40 mg (F) and of frusemide 40 mg in combination with a single dose of triamterene 50 mg (F+T). F as well as F+T induced significant increases in volume, sodium and magnesium mean 24 h output as compared with 24 h renal excretion without medication. Addition of triamterene to frusemide significantly reduced the 24 h potassium excretion, but did not attenuate the excretion of magnesium. The time to reach the maximum magnesium excretion rate after F as well as after F+T administration was similar to that of the sodium excretion rate. We conclude that triamterene does not inhibit the magnesiuric effects of frusemide in healthy male adults.

Administration, Oral↗