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Biomedical subjects

T Hedner

Publications and source records attributed to T Hedner.

At least 343 records · Page 19Linked to original sources
PubMed1985

Antihypertensive properties of ketanserin in combination with beta-adrenergic blocking agents.

The antihypertensive effect of ketanserin in combination with beta-adrenergic blockade was assessed in a double-blind crossover (4 weeks) manner in 10 patients with essential hypertension. The addition of ketanserin (40 mg b.i.d.) to optimal doses of beta-adrenergic blockers had significant antihypertensive effects compared with treatment with beta-adrenergic blockers alone. When followed for 24 h at steady-state conditions, ketanserin effectively reduced the blood pressure during a major part of the day, with maximal effect occurring at the time of the peak plasma concentration of ketanserin (1-2 h after tablet intake). Six patients initially reported a slight sedation during ketanserin treatment.

Adrenergic beta-Antagonists↗
PubMed1985

A double-blind evaluation of topical levocabastine, a new specific H1 antagonist in patients with allergic conjunctivitis.

Forty patients suffering from allergic conjunctivitis, due to birch pollen, participated in a double-blind parallel group comparison between levocabastine (a potent new specific histamine (H1) antagonist) and placebo, both given as eye drops. Symptom scores were recorded during a 4-week period. A 1-week run-in period was followed by a 3-week treatment period. To enable a fair evaluation of the treatment effect on the ocular symptoms only, all patients were treated with topical nasal glucocorticoids for possible rhinitis symptoms during the whole study period. Plasma levels of levocabastine were determined in all subjects at the end of the 3 weeks' treatment period. Pollen counts for birch pollen were followed simultaneously. The evaluation of the symptom score cards revealed a significant reduction of ocular symptoms following use of the active compound. The resorption of the active substance through the conjunctiva was low. In accordance with the present trend of more topical treatment for allergic rhinitis, levocabastine may constitute a valuable compound for the topical treatment of allergic conjunctivitis.

Adolescent↗
PubMed1985

Cardiovascular effects in the Sprague-Dawley rat of 8-hydroxy-2(di-N-propylamino) tetralin, a selective 5-hydroxytryptamine receptor agonist.

The intravenous administration of 8-hydroxy-2(di-N-propylamino) tetralin, a selective 5-HT receptor agonist, caused a biphasic blood pressure response and bradycardia in Sprague-Dawley rats. The initial pressor response involved peripheral alpha 1-adrenoceptors since it was present in pithed rats and was antagonized by prazosin. Though the intracerebroventricular route of administration was not more effective the hypotension and bradycardia were probably of central origin. The bradycardia was prevented by pretreatment with atropine and propranolol suggesting an involvement of vagal as well as sympathetic activity. These results support the view that central 5-HT receptor activation reduces the blood pressure and heart rate.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1985

Characterization of adenosine-induced respiratory depression in the preterm rabbit.

The respiratory performance was studied after intraperitoneal administration of the adenosine agonists N6-phenyl-isopropyl-adenosine (PIA) and adenosine-5-ethylcarboxamide to preterm (gestational age 29-30 days) newborn halothane-anesthetized rabbits. Both agonists induced marked hypoventilation and irregular breathing by decreases in the breathing frequency as well as the tidal volume. Expiratory time was markedly prolonged, resulting in a decrease in the respiratory duty cycle (inspiratory time/total cycle duration). Analysis using the occluded-breath technique revealed that the adenosine analogues altered the time setting of the expiratory (inspiratory) neuronal circuits and lowered the inspiratory off-switch level, while inspiratory drive and the bulbopontine setting of the inspiratory phase were unaltered. The ventilatory response to CO2 was blunted after both adenosine analogues studied. Theophylline almost completely reversed the hypoventilation and irregular breathing seen after PIA injection. It is concluded that activation of central nervous adenosine receptors induced a marked respiratory depression in the preterm rabbit. Furthermore, our data imply that an overactivity of central adenosine mechanisms may have a pathophysiological significance for the irregular breathing or apnea of prematurity sometimes seen in the human neonate.

Adenosine↗
PubMed1985

Felodipine. A calcium-inhibiting vasodilator in refractory hypertension.

12 patients with primary hypertension not adequately controlled on combined treatment with diuretics, beta-adrenergic blocking drugs and hydralazine were included in the study. The patients were hospitalised and hydralazine discontinued. The diuretic and beta-blocking medication was given about 1 hour prior to the short term experiments and, following baseline measurements, an oral solution of felodipine (0.075-0.1 mg/kg) was ingested. Cardiac output was measured (dye dilution technique) and continuous monitoring of intra-aortic blood pressure (brachial artery) was performed. In 10 patients, changes in renal plasma flow (para-aminohippuric acid clearance) and glomerular filtration rate (51Cr-EDTA-clearance) were followed over a short period, and in 6 patients repeated after 5 to 7 months. Plasma renin activity (radioimmunoassay of angiotensin I) was followed, as was plasma concentration of felodipine. A significant hypotensive response was seen only 15 minutes after intake of felodipine. The maximal response occurred after 30 minutes when mean arterial blood pressure was reduced by 24% (from 132 to 102 mm Hg). There was a linear relationship between the change in mean arterial blood pressure and log plasma concentration of felodipine. Cardiac output increased from 5.1 +/- 1.5 to 6.6 +/- 2.6 L/min (p less than 0.01), partly because of increased heart rate from 56 +/- 7.9 to 65 +/- 9.5 beats/min (p less than 0.01) and partly due to increased stroke volume from 93 +/- 25 to 103 +/- 34 ml/beat (p less than 0.05). Renal plasma flow increased significantly (p less than 0.05) from 343 +/- 138 ml/min to 391 +/- 154 ml/min and 400 +/- 149 ml/min, while glomerular filtration rate did not change.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Antihypertensive effects of felodipine compared with placebo.

The effects of felodipine and placebo on blood pressure, heart rate and tolerability were investigated in 4 different groups of patients. One group had not received previous therapy, whereas the other 3 groups received concomitant antihypertensive compounds (beta-blockers, diuretics or beta-blocker + diuretics). The haemodynamic effects and tolerability were studied after a single dose, as well as during steady-state conditions. After a single dose of felodipine there was a rapid and significant decrease in blood pressure and increase in heart rate with felodipine alone as well as with combination therapy. During long term treatment, blood pressure was significantly decreased after felodipine during the dosing interval (12h), irrespective of concomitant treatment. Heart rate, however, was not increased, even in patients without a beta-blocker. The reduction in blood pressure was correlated with the plasma concentration of felodipine after single-dose administration, but not during long term treatment. Felodipine was generally well tolerated. In the short term, headache was the most common side effect, while swelling of the ankles was the most frequent adverse effect during long term treatment. In conclusion, felodipine is a promising antihypertensive compound, which may be used in the treatment of high blood pressure, either alone or in combination with other agents.

Adrenergic beta-Antagonists↗
PubMed1985

Long term experience of felodipine in combination with beta-blockade and diuretics in refractory hypertension.

Felodipine, a new dihydropyridine, was given to 58 hypertensive patients in combination with an adrenergic beta-receptor antagonist and a diuretic agent. In all but 2 patients the blood pressure was unsatisfactorily controlled on standard triple therapy, i.e. alpha beta-blocker, a diuretic and a vasodilator. A 48-week follow-up was completed by 54 patients. After an initial dose titration period, the maintenance dose of felodipine was 5 mg twice daily in 14 patients and 10 mg twice daily in 34 patients. In the remaining 6 patients, the dose ranged from 5 mg every morning to 25 mg twice daily. The dosages of beta-blocking agent and diuretic were considerably reduced during the study period. Mean supine blood pressure was reduced from 170/101 mm Hg on triple therapy before felodipine to 145/86 mm Hg (p less than 0.001) after 2 weeks on felodipine. This improvement was sustained throughout the study and was measured at 144/86 mm Hg (p less than 0.001) after 48 weeks. There was no increase in resting heart rate and no orthostatic fall in blood pressure. Bodyweight was not increased and felodipine was generally well tolerated. Three patients were withdrawn owing to side effects and 1 was socially non-compliant. It is concluded that felodipine is a potent and well tolerated vasodilator, and will be useful in the long term combination treatment of previously refractory hypertension.

Adrenergic beta-Antagonists↗
PubMed1985

Plasma atrial natriuretic peptide and haemodynamics in conscious normotensive and spontaneously hypertensive rats after acute blood volume expansion.

The atrial natriuretic peptides (ANP) are a family of newly discovered peptides which are released from atrial tissue and have potent diuretic/natriuretic, vasodilating and aldosterone inhibitory properties. Plasma concentration of ANP was measured and related to haemodynamic changes after acute blood volume expansion (10 and 20%) in normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). Acute blood volume expansion resulted in an increase in central (CBV) and peripheral blood volume (PBV), central venous pressure (CVP), stroke volume (SV) and cardiac output (CO), while total peripheral resistance (TPR) and heart rate (HR) were decreased. Mean arterial pressure (MAP) was unchanged. There were larger increases in CBV, CVP and CO in SHR than in WKY rats. In contrast, the increase in PBV and the decrease in HR were more marked in the WKY rats. Basal plasma ANP concentrations were similar in both groups. Blood volume expansion caused a linear increase in plasma ANP in the WKY rats, while the increase in plasma ANP concentration was attenuated in the SHR. It is concluded that acute blood volume expansion is more centralized in the SHR than in the WKY rats. Interestingly, the ANP release in response to blood volume expansion seems to be attenuated in SHR compared with WKY rats, as maximal plasma ANP concentrations were found at 10% volume load.

Animals↗
PubMed1985

Fluid homeostasis and haemodynamics during sodium restriction in hypertensive men.

To investigate the antihypertensive effect of moderate sodium restriction, the sodium intake of 11 male outpatients was reduced by 120 mmol/day for 4-6 weeks. These patients and an untreated control group were slightly obese and had mild untreated hypertension (WHO 1-2). All subjects were examined before and at the end of the experiment. Diastolic blood pressure fell significantly in the diet group in comparison with the control group. Invasive haemodynamic examinations in the diet group showed an unchanged mean cardiac output and a reduction of mean total peripheral resistance. Plasma volume (Evan's Blue) did not change, neither did extracellular volume as calculated from determinations of tritiated water, total body potassium and body mass. During sodium restriction, plasma renin activity and urinary aldosterone excretion significantly increased. Noradrenaline and dopamine excretion in urine showed no significant changes during sodium restriction, neither did the plasma concentrations of atrial natriuretic peptides. The reduction in mean arterial blood pressure was correlated significantly with a decrease in 24-h sodium excretion and an increase in urinary aldosterone excretion. In conclusion, moderate dietary sodium restriction seems to lower blood pressure by diminishing the total peripheral resistance while cardiac output, extracellular and intravascular volumes are maintained.

Body Fluids↗
PubMed1984

Adenosine mechanisms in the regulation of breathing in the rat.

The central respiratory effects of various adenosine (A) analogues were studied in halothane-anesthetized rats. Intracerebroventricular (i.c.v.) and intraperitoneal (i.p.) injections of the A analogues (2-Cla, L-PIA, CHA and NECA) reduced minute ventilation (VE) due to decreases in respiratory frequency (f) as well as tidal volume (VT). Dose-dependent effects were seen after i.c.v. L-PIA in both normal and vagotomized rats. Analysis of the A-induced changes using the occluded breath technique revealed an increase in expiratory time (TE) as well as a decrease in inspiratory drive. NECA, a relatively specific A2 agonist seemed to be somewhat more potent in eliciting respiratory depression than a relatively specific A1 agonist like L-PIA. Pretreatment with the methylxanthine theophylline completely antagonized the respiratory depression induced by L-PIA. It is concluded that central A receptors are involved in the central regulation of breathing and that A interacts with the respiratory control system mainly by decreasing inspiratory neural drive and prolonging expiratory time.

Adenosine↗
PubMed1984

Antihypertensive effects of chronic 5-hydroxytryptamine (5-HT2) receptor blockade with ketanserin in the spontaneously hypertensive rat.

The effects of chronic oral treatment with the 5-hydroxytryptamine (serotonin) receptor blocking agent ketanserin (17 mg/100 g dry food) on blood pressure, heart weight, peripheral vascular reactivity, baroreceptor sensitivity, central cardiovascular reactivity and central catecholamine turnover were investigated in the spontaneously hypertensive rat. Blood pressure measurements were performed in conscious rats 24 h after insertion of catheters. After 6 weeks treatment basal blood pressure was reduced (16%) compared to control rats (given identical food, except for ketanserin). Both heart weight and body weight were reduced (both to 93% of control values) leaving heart weight/body weight ratio unchanged. Pressor responses to phenylephrine and depressor responses to isoprenaline (after pretreatment with reserpine and atropin) were not different while the blood pressure increase to 5-hydroxytryptamine was inhibited, indicating that after 6 weeks treatment the blood pressure reduction is not directly related to alpha-adrenoceptor blockade. Cardiovascular response to stress (jet air), baroreceptor sensitivity (bradycardia to phenylephrine) and central catecholamine synthesis rates (accumulation of 5-hydroxytryptophan and dihydroxyphenylalanine after synthesis inhibition) were unchanged supporting earlier evidence that central mechanisms probably do not contribute to the hypotensive effects of ketanserin.

Animals↗
PubMed1984

Pharmacokinetics of epidural morphine in man.

Cerebrospinal fluid (CSF) and plasma morphine concentrations were determined in 5 patients after epidural administration of 6 mg morphine; plasma samples were collected frequently during the initial 6 h and 6-7 CSF samples were obtained from each patient over a 24 h period. Morphine was analysed using gas chromatography and electron capture detection. Individual morphine concentration-time curves were plotted for plasma and CSF and various pharmacokinetic variables were calculated. Plasma morphine concentrations after epidural injection were similar to those found after intramuscular administration; Cmax (66 +/- 8 mg/ml: mean +/- SEM) appeared within 12 +/- 3 min, and the terminal elimination half-life in plasma was 213 +/- 24 min. In CSF, morphine reached a peak (1575 +/- 359 ng/ml) after 135 +/- 40 min. The terminal elimination half-life for morphine in CSF was 239 +/- 10 min. The CSF bioavailability of morphine after epidural administration was calculated to be 1.9 +/- 0.5%. The study showed that epidural administration of morphine resulted in CSF concentrations many times higher than those in plasma, but still only 2% of the dose administered was available to the CSF compartment. Morphine was eliminated with similar speed from CSF and plasma.

Biological Availability↗
PubMed1984

Central GABA mechanisms during postnatal development in the rat: neurochemical characteristics.

Various biochemical characteristics of the developing GABA system was studied in rats from 1 to 60 days of age. Endogenous GABA concentrations were high in the limbic system, midbrain, brain stem and spinal cord at birth. Until 7 days of postnatal age, GABA concentrations generally decreased, thereafter an increase was seen and at 60 days of age the GABA concentrations exceeded those found in the neonate except for the spinal cord regions. After GABA-T inhibition with AOAA, GABA concentrations increased in all brain regions, however considerably more marked in the 28 days old rats compared to the 4 days old animals. Turnover rate of GABA was estimated by investigating the rate of disappearance of GABA after GAD inhibition with 3-MPA. Calculated turnover time of whole brain GABA was 34.1 min in the 4 days old rats and 19.9 min in the 28 days old animals. The results from this investigation clearly indicate a caudal to rostral maturational gradient in the development of endogenous GABA concentrations as well as synthesis capacity. Furthermore, turnover rate of total whole brain GABA but probably not of GABA in the neuronal pool is retarded in the 4 days old rats compared to the adolescent animals.

3-Mercaptopropionic Acid↗
PubMed1984

Increased erythrocyte sodium efflux during overfeeding without evidence of mediation by circulating catecholamines or thyroid hormone.

Ten slightly obese middle-aged men were instructed to increase their energy intake 25% during a period of 1 week, which was preceded by a control period of seven days. Body weight increased by 0.67 kg (SD 0.60) indicating good compliance with the regimen. Transmembrane sodium fluxes were determined with the use of 22Na. The pre-diet erythrocyte sodium content was 9.7 mmol/L (SD 0.8) decreasing to 8.9 mmol/L (SD 1.1) (P less than 0.05) during overfeeding. The Na-efflux rate constant increased from 0.40 h-1 to 0.54 h-1 (P less than 0.05). Urinary excretion of catecholamines and concentrations of catecholamines and insulin in plasma and of thyroxine, triiodothyronine, and reverse T3 in serum did not change. Thus, overfeeding seems to enhance the total Na efflux in erythrocytes from slightly obese men. There were no measurable changes in thyroid hormone or catecholamine levels leaving the regulatory mechanisms unexplained.

Adult↗
PubMed1984

Guanfacine in essential hypertension: effects during rest and isometric exercise.

The antihypertensive effects of guanfacine (0.5 to 4 mg daily) were investigated for 1 yr in 13 patients with essential hypertension. Blood pressure (BP) and heart rate (HR) response was measured during isometric exercise (handgrip) before starting the therapy, after 1 yr of treatment, and 2 wk after withdrawal. Guanfacine in once-daily dosage reduced BP during rest (supine BP: control, 175 +/- 6/103 +/- 4 mm Hg; 1 yr guanfacine, 161 +/- 5/91 +/- 3 mm Hg). Steady-state plasma concentrations after 1 yr were 4.1 +/- 0.59 ng/ml. Resting plasma norepinephrine (NE) and epinephrine (E) levels were lower during active therapy than 2 wk after withdrawal (guanfacine and control: plasma NE, 0.27 +/- 0.03/0.64 +/- 0.13 ng/ml; plasma E, 0.09 +/- 0.02/0.17 +/- 0.05 ng/ml). The relative reduction of plasma catecholamines (guanfacine and withdrawal) was of the same order during handgrip exercise as during supine rest. During isometric handgrip exercise, BP was lower during guanfacine therapy than before treatment and 2 wk after withdrawal, but the increment in BP during handgrip exercise was not affected by the drug despite the lower BP values on therapy. Our data indicate that the central alpha 2-agonist action of guanfacine reduces sympathoadrenal function equally during rest and isometric exercise.

Blood Pressure↗
PubMed1984

Blood pressure and intra-erythrocyte sodium during normal and high salt intake in middle-aged men: relationship to family history of hypertension, and neurogenic and hormonal variables.

During 4 weeks 37 normotensive 50-year-old men identified by screening in a random population sample were given 12 g of NaCl daily, in addition to their usual dietary sodium intake. Blood pressure, heart rate, weight, urinary excretion of sodium, potassium and catecholamines, plasma aldosterone and noradrenaline and intra-erythrocyte sodium content were determined on normal and increased salt intake. The subjects were divided into those with a positive family history of hypertension (n = 11) and those without such a history (n = 26). Systolic blood pressure and weight increased significantly irrespective of a positive family history of hypertension. On normal salt intake intra-erythrocyte sodium content was significantly higher in those with a positive family history of hypertension. During high salt intake intra-erythrocyte sodium content decreased significantly in that group and the difference between the hereditary subgroups was no longer significant. In the whole group urinary excretion of noradrenaline, adrenaline and dopamine increased whereas plasma aldosterone decreased during the increased salt intake. Thus, in contrast to some earlier studies performed in young subjects, our results indicate that moderately increased sodium intake acts as a pressor agent in normotensive middle-aged men whether there was a positive family history of hypertension or not. We confirm that men with positive family history of hypertension have an increased intra-erythrocyte sodium content, and that an increase in salt intake seems to increase overall sympathetic activity.

Aldosterone↗
PubMed1984

Pharmacokinetic aspects of intrathecal morphine analgesia.

Fifteen patients undergoing thoracotomy were given 0.25 or 0.50 mg morphine intrathecally (L2-L3 or L3-L4) for an analgetic and pharmacokinetic study. Administration of morphine at the end of the operation resulted in a highly variable duration of analgesia ranging from 1-20.5 and 1-40 h for the 0.25 and 0.50 mg groups, respectively. Calculation of cumulative consumption pattern of additional analgesics given im indicated a dose-related analgesia lasting around 12 h. Morphine concentrations in the CSF were high and dose dependent. Thus, at 1 h, CSF concentrations (means +/- SEM) were 4,228 +/- 361 ng/ml and 10,447 +/- 1,538 ng/ml for the 0.25 and 0.50-mg groups, respectively. The plasma concentrations generally were very low, i.e., under 1 ng/ml. For the 0.50 and 0.25 mg groups, the terminal elimination half-life in CSF was 175 +/- 9 min and 196 +/- 13 min, respectively: the volume of CSF distribution was 0.88 +/- 0.16 ml X kg-1 and 1.06 +/- 0.17 ml X kg-1, respectively: and the clearance from CSF was 2.81 +/- 0.41 microliter X kg-1 X min-1 and 3.41 +/- 0.55 microliter X kg-1 X min-1, respectively (means +/- SEM). The study indicates that the significant pharmacokinetic parameter related to the long duration of analgesia after intrathecal morphine administration probably is the high CSF concentrations found, since the rate of elimination from CSF is similar to what is reported for morphine in plasma. Furthermore, modulation of nociceptive input in the thoracic region also may be achieved by lumbar administration, but a slower onset should be anticipated.

Aged↗