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Biomedical subjects

S Sundberg

Publications and source records attributed to S Sundberg.

At least 37 records · Page 2Linked to original sources
PubMed1994

COMT inhibition by high-dose entacapone does not affect hemodynamics but changes catecholamine metabolism in healthy volunteers at rest and during exercise.

We studied the effects of catechol-O-methyltransferase (COMT) inhibition with entacapone on hemodynamics and catecholamine metabolism in healthy volunteers at rest and during a bicycle exercise test. Entacapone was given orally during two periods of seven days each to eleven healthy male volunteers; on the first period 400 mg t.i.d. and on the second 800 mg t.i.d. A submaximal exercise test giving a heart rate of about 163-167 beats/min with the highest predetermined work load was performed on a bicycle ergometer, and blood pressure, heart rate and ECG were recorded. The concentrations of adrenaline, noradrenaline, 3,4-dihydroxyphenylglycol (DHPG), 3-methoxy-4-hydroxyphenylglycol (MHPG) and 3,4-dihydroxyphenylacetic acid (DOPAC) in plasma were determined. Blood pressure, heart rate, ECG, and plasma concentrations of unconjugated adrenaline and noradrenaline were not influenced after single and repeated dosing of entacapone. The plasma concentrations of DHPG (a monoamine oxidase (MAO)-dependent metabolite) increased maximally by 245% compared to the control day. DOPAC (a MAO-dependent metabolite) increased maximally by 144% and MHPG (a COMT-dependent metabolite) decreased by 54%. The increase in DHPG and DOPAC was significantly greater with the 800 mg dose than with the 400 mg dose. The decrease in MHPG was significantly greater with the repeated dosing than with the single dose of entacapone. COMT inhibition by entacapone seems not to affect hemodynamics or plasma concentrations of unconjugated adrenaline and noradrenaline in healthy volunteers either at rest or during exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dihydroxyphenylacetic Acid↗
PubMed1993

The effects of the COMT inhibitor nitecapone for one week on exercise haemodynamics and catecholamine disposition.

We have studied resting and exercise haemodynamics and catecholamine disposition after catechol-O-methyl-transferase (COMT) inhibition with nitecapone 100 mg t.d.s. for 7 days in 15 healthy men (aged 21 to 28 y) in a placebo-controlled, cross-over study. Nitecapone did not alter resting or exercise heart rates, blood pressure, or plasma catecholamine concentrations, but it altered the metabolic profile of endogenous catecholamines, as shown by: (1) a fall in the concentrations of the COMT-dependent metabolite 3-methoxy-4-hydroxy-phenylglycol (MHPG) by 22% (P < 0.01), (2) increases in plasma concentrations of the monoamine oxidase-dependent metabolites 3,4-dihydroxyphenylglycol (DHPG) by up to 90% (P < 0.001) and 3,4-dihydroxyphenylacetic acid (DOPAC) by 67% (P < 0.05), (3) a three-fold increase in the concentration of circulating conjugated adrenaline (P < 0.001).

Adult↗
PubMed1993

The effects of the COMT inhibitor entacapone on haemodynamics and peripheral catecholamine metabolism during exercise.

1. Catechol-O-methyltransferase (COMT) inhibition might be assumed to potentiate the effects of circulating catecholamines, particularly under conditions of enhanced catecholamine release. 2. The purpose of the present study was to establish whether the novel COMT inhibitor, entacapone, changes haemodynamic responses and catecholamine metabolism during exercise. 3. Entacapone was given orally to 12 healthy male subjects (age 23-30 years) in increasing single doses from 0 mg (control day) to 200 mg. A submaximal exercise test was performed on a bicycle ergometer, and blood pressure, heart rate and ECG were recorded. The concentrations of noradrenaline, adrenaline, DHPG (3,4-dihydroxyphenylglycol), MHPG (3-methoxy-4-hydroxyphenyl-glycol) and, DOPAC (3,4-dihydroxyphenylacetic acid) in plasma were determined. 4. Entacapone did not influence haemodynamics or ECG at rest or during exercise. 5. Entacapone did not influence plasma catecholamine levels, either at rest or during exercise. However, it altered the metabolic profile of catecholamines, which was shown by increases in the plasma concentrations of the monoamine oxidase-dependent metabolites DHPG (by up to 100%) and DOPAC (by up to 53%), and by a decrease of the COMT-dependent metabolite MHPG (by up to 29%).

Administration, Oral↗
PubMed1992

Efficacy of conventional and sustained-release verapamil in stable angina pectoris.

The efficacy of sustained-release (s.r.) verapamil and conventional verapamil were compared in a double blind, crossover study in 20 patients (age 53 +/- SD6 years) who had stable effort angina and had used betablockers and long acting nitrates for at least two weeks. All patients received s.r. verapamil 200 mg b.i.d. and conventional verapamil 120 mg t.i.d. in a randomised order for two weeks. A symptom limited bicycle exercise test was performed at the end of the patients' previous medication period with betablocker plus long acting nitrate and at the end of both verapamil treatments in the morning before drug administration and three hours thereafter. All the patients improved subjectively during both verapamil regimens according to NYHA classification and they had fewer anginal attacks. The time to onset of ST-segment depression during exercise remained shorter during beta-blockade and long acting nitrates than during both verapamil regimens (P less than 0.05). During the peak action three hours after drug administration conventional verapamil was most effective at comparable workloads (P less than 0.05), whereas the exercise time was slightly prolonged with s.r. verapamil before drug administration.

Adrenergic beta-Antagonists↗
PubMed1991

COMT inhibition with nitecapone does not affect the tyramine pressor response.

Nitecapone (OR-462) is a new selective COMT inhibitor with gastroprotective properties. The aim of the present study was to determine whether nitecapone potentiates the haemodynamic effects of a tyramine-induced increase in catecholamine release. The systolic blood pressure response to tyramine was studied in 11 healthy male volunteers (age 20-32 years). Tyramine was given i.v. as rapid bolus injections in increasing doses without drug intake and after oral intake of single doses of 25 mg and 100 mg of nitecapone. The tyramine dose required to increase systolic blood pressure by 30 mm Hg ('pressor dose') was 4.98 mg, 5.04 mg and 4.88 mg after no medication, and with 25 mg and 100 mg of nitecapone, respectively. There were also no differences in the systolic blood pressure response vs time curves between the three regimens. COMT inhibition with nitecapone did not potentiate the haemodynamic responses to tyramine-induced catecholamine release.

Adult↗
PubMed1990

Exercise hemodynamics and catecholamine metabolism after catechol-O-methyltransferase inhibition with nitecapone.

The effect of catechol-O-methyltransferase inhibition with nitecapone (OR-462) on the hemodynamic responses to exercise and catecholamine metabolism was studied in 10 healthy male volunteers (aged 19 to 26 years). Nitecapone, a new specific and selective catechol-O-methyltransferase inhibitor, was given at increasing single oral doses up to 100 mg. Nitecapone did not influence resting or exercise heart rate, blood pressure, systolic time intervals, or plasma catecholamine levels. It altered the metabolic profile of catecholamines as shown by (1) an increase of 140% in the plasma concentration of the monoamine oxidase-dependent metabolite 3,4-dihydroxyphenylethyleneglycol (p less than 0.001), (2) a decrease of 27% in the plasma concentration of its methylation product 3-methoxy-4-hydroxyphenylethyleneglycol (p less than 0.05), and (3) a 25% reduction in the urinary excretion of the methylated metabolites 3-methoxy-4-hydroxymandelic acid and homovanillic acid (p less than 0.05). Nitecapone was well tolerated and seemed to be hemodynamically safe in humans.

Adult↗
PubMed1990

Effects of captopril on blood pressure and respiratory function compared to verapamil in patients with hypertension and asthma.

Seventeen adult patients with moderate and stable bronchial asthma and established essential hypertension (WHO I or II) were evaluated in a randomized, double-blind, crossover study of the effects of captopril (50-100 mg/day) and verapamil (160-240 mg/day) on blood pressure, orthostatic reactions, respiratory function, and asthmatic symptoms. The effect of both drugs on blood pressure was significant. Blood pressure (mean of 161/98 mm Hg initially) decreased to a mean of 147/90 and 160/91 mm Hg on captopril and verapamil, respectively, with normal orthostatic changes. There were no significant differences in forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), maximal expiratory flow at 50% of FVC (MEF50), or peak expiratory flow (PEF) measurements at the end of each treatment period. The subjective severity of asthma did not change significantly during the trial. No significant cough symptoms were reported on captopril.

Aged↗
PubMed1989

Comparison of potassium alone and potassium-magnesium supplementation in patients with heart failure using hydrochlorothiazide.

Supplementation of potassium alone and in combination with magnesium was compared in 10 patients with chronic compensated heart failure receiving hydrochlorothiazide 50 mg twice daily for the whole trial. After a 3-week run-in period, the patients were randomized to receive active supplementation for 6 weeks in a double-blind cross-over manner. A 3-week wash-out period was kept in between. Addition of 2 g potassium chloride daily (27 mmol K+) did not efficiently correct the serum potassium concentration. After the combined supplementation of 2 g potassium and 1 g magnesium (27 mmol K+ and 17 mmol Mg2+ daily), both serum potassium and magnesium concentrations increased statistically significantly during the first 2 weeks of treatment. After a longer treatment of 6 weeks, the effect of combined supplementation was less clear, even though a trend toward a better maintenance of serum potassium was still evident.

Aged↗
PubMed1988

Rapid reversal of circadian blood pressure rhythm in shift workers.

The blood pressure and heart rates of seven normotensive shift workers were monitored automatically for 24 h with a non-invasive ambulatory method on 3 different days. The first monitoring session took place at the end of an ordinary work period of morning shifts, the second on the first day of a period of night shifts, and the third on the last day of a period of night shifts. The circadian blood pressure rhythm, which showed a normal pattern during the daytime work shift, was totally reversed from the first day of the night shift. The blood pressure rhythm closely followed the sleep-wakefulness cycle. The changes in circadian heart rate rhythm were not as pronounced as those in blood pressure but showed a similar trend.

Adult↗
PubMed1987

Exercise capacity and hemodynamics in persons aged 20 to 50 years with systemic hypertension treated with diltiazem and atenolol.

Hemodynamic responses and exercise capacity were studied during maximal exercise in 25 young hypertensive persons (mean age 40 years) taking placebo, diltiazem (mean 216 mg/day) and atenolol (mean 80 mg/day). The study was a crossover, double-blind, randomized trial, each medication period lasting 2 months. Sitting blood pressure (BP) was 160 +/- 19/109 +/- 8 mm Hg after run-in. Both drugs decreased BP significantly, diltiazem by 10/ 11 mm Hg and atenolol by 16/14 mm Hg (difference not significant between drugs). During exercise there were no differences among patients taking placebo, diltiazem and atenolol in peak workload and rating of perceived exertion. Atenolol significantly attenuated the increase in heart rate, BP and heart rate-BP product at each workload. Diastolic BP during exercise was significantly lower (6 to 10 mm Hg) during diltiazem therapy than during placebo at each workload. Thus, both diltiazem and atenolol decrease rest BP significantly without impairing exercise capacity.

Adult↗
PubMed1987

Noninvasive, automatic 24-h ambulatory blood pressure monitoring in normotensive subjects.

The reliability of noninvasive, automatic blood pressure monitoring is not yet clearly established. A 24-h ambulatory blood pressure profile was obtained in 9 healthy, normotensive subjects with an automatic, noninvasive device. The blood pressure profile showed the typical circadian pattern with lower systolic and diastolic values during sleep, although pulse pressure was fairly constant (about 40 mm Hg). The systolic blood pressure rose steeply in the early morning hours--before waking up. The results were compared with simultaneous hourly readings using the auscultatory method. There were no statistically significant differences between the automatic and auscultatory readings, 13 of the 18 mean values at different time points being within 2 mm Hg of each other. All the auscultatory means fell within the 95% confidence limits of those measured hourly by the automatic method. Although the automatic method seemed to be reliable compared with the auscultatory method, its sensitivity to motion artifacts is a disadvantage in a truly ambulatory setting.

Adult↗
PubMed1987

Vasodilatory effects of carvedilol and pindolol.

The effects of three different nonselective beta-blockers on central and peripheral hemodynamics as well as on pulmonary function were compared in 13 healthy subjects (19-37 years). The subjects were given carvedilol 50 mg, pindolol 10 mg, propranolol 80 mg, and placebo orally twice daily for 1 week in a double-blind, crossover, randomized manner. Heart rate, blood pressure, arterial calf blood flow (venous occlusion strain gauge plethysmography), and pulmonary function (flow-volume spirometry) were measured at the first and at the last trial day. Heart rate and blood pressure were lower on carvedilol and propranolol than on pindolol and placebo; the maximal bradycardiac effect was 13 and 17 beats/min and hypotensive effect 9/10 mm Hg and 10/7 mm Hg on carvedilol and propranolol, respectively. Both carvedilol and pindolol increased arterial flow by about 40% (p less than 0.05 and p less than 0.01, respectively) and reduced peripheral resistance by about 34% (p less than 0.05 and p less than 0.01, respectively), the effect persisting after 1 week of treatment. None of the medications had any noteworthy effects on pulmonary function. Two subjects complained of tremor on pindolol. We conclude that carvedilol and pindolol possess distinct vasodilatory properties. Carvedilol had a stronger hypotensive effect than pindolol and was well tolerated.

Adrenergic beta-Antagonists↗
PubMed1986

Influence of beta blockade and intrinsic sympathomimetic activity on hemodynamics, inotropy and respiration at rest and during exercise.

The degree of intrinsic sympathomimetic activity (ISA) is reported to influence the effects of beta blockade at rest, but the effects during exercise are not well documented. Heart rate, blood pressure and left ventricular (LV) function (as assessed by systolic time intervals) were measured at rest and during upright bicycle exercise as well as with flow-volume spirometry at rest in 13 healthy volunteers. The measurements were performed before and 4 and 24 hours after a single oral dose of pindolol (10 mg), nadolol (80 mg) and acebutolol (400 mg) in a double-blind, randomized, crossover manner. All drugs reduced heart rate, but nadolol had the most pronounced and longest bradycardic effect at rest. Diastolic blood pressure was only slightly influenced by the drugs, whereas systolic pressure was significantly lower compared with control values, especially during exercise (p less than 0.001). Neither preejection period (PEP) nor LV ejection time (LVETc) was changed at rest after pindolol, but PEP increased and LVETc decreased significantly after nadolol (p less than 0.05 for PEP and p less than 0.01 for LVETc) and acebutolol (p less than 0.05 for both). During exercise, PEP and LVET were significantly longer after all 3 drugs compared with control values. Only nadolol, which lacks ISA, significantly decreased expiratory flow values (p less than 0.05). Thus, unlike the other beta blockers, pindolol (with strong ISA) did not depress LV function at rest, while during exercise all 3 beta blockers had equal adverse effects. The degree of ISA appears to be important in determining the hemodynamic effects of beta-blocking drugs.

Acebutolol↗
PubMed1986

An alternative method for calculating changes in arterial calf blood flow at rest. An initial study.

In 20 patients we studied the changes in calf arterial blood flow (AF) following spinal and epidural blocks, using venous occlusion strain gauge plethysmography (SGP). AF was calculated both in the conventional way by drawing a tangent to the initial upslope of the curve, and by a new method which measures the time to the point when 50% of venous capacity is reached (tVC50). The statistical differences within and between the spinal and epidural groups for AF and tVC50 were determined. In measuring the post-block changes in AF as compared with the control values, a statistically significant correlation (rs = -0.85, p less than 0.01) was observed between the two methods. We conclude that the new variable, tVC50, seems to be potentially useful in calculating changes in arterial blood flow at rest, and could be used, for example, in connection with surgical and pharmacological interventions, especially when the initial upslope of the SGP curve is equivocal.

Adult↗