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Biomedical subjects

T Hedner

Publications and source records attributed to T Hedner.

At least 271 records · Page 15Linked to original sources
PubMed1988

Is high and fluctuating muscle nerve sympathetic activity in the sleep apnoea syndrome of pathogenetic importance for the development of hypertension?

Muscle nerve sympathetic activity was recorded in six patients with the sleep apnoea syndrome (SAS). Compared with age- and sex-matched control patients, an increased activity during wakefulness was found. Sleep apnoic events were associated with sequencies of progressively increasing sympathetic activity followed by a sudden reduction of activity. The high sympathetic activity associated with SAS may be important in the development of the systemic hypertension commonly seen in these patients.

Blood Pressure↗
PubMed1988

Acute effects of short-term fasting on blood pressure, circulating noradrenaline and efferent sympathetic nerve activity.

Eleven moderately obese women, aged 46-62 years, with a body mass index of 29-34 and with borderline hypertension (repeated diastolic blood pressure greater than 90 mmHg) fasted for 48 hours. Before the fast and after 48 hours of fasting, plasma noradrenaline, urinary noradrenaline, urine potassium, urine sodium and weight were measured. In six of the patients muscle nerve sympathetic activity was recorded from the peroneal nerve by tungsten microelectrodes for 15 min each time. The efferent muscle sympathetic activity (MSA) was expressed as the number of bursts/min. The recordings were done before the fast and after 48 hours of fasting. We found significant decreases in body weight from 88.4 +/- 2.5 kg to 86.4 +/- 2.5 kg. Systolic blood pressure (BP) was reduced from 158 +/- 3 mmHg to 146 +/- 5 mmHg (p less than 0.001) and diastolic BP from 96 +/- 3 mmHg to 89 +/- 3 mmHg (p less than 0.01) during the fast. MSA was significantly increased from 42.0 +/- 5.5 bursts/min to 44.5 +/- 5.8 (n = 6), while plasma and urine noradrenaline concentrations (n = 11) showed a non-significant tendency to increase. We conclude that the hypotensive response during the first days of extensive caloric reduction is not due to a decreased sympathetic activity. If anything, there may be weak increase of efferent sympathetic nerve activity and venous plasma levels of circulating noradrenaline. The mechanisms behind the acute hypotensive response to negative caloric balance are thus still unclear, but obviously different from long-term adaptation of the blood pressure.

Blood Pressure↗
PubMed1988

Influence of intraperitoneal anesthesia on pain and the sympathoadrenal response to abdominal surgery.

The effects of intraperitoneal administration of bupivacaine on pain and the sympathoadrenal response to surgery were studied in a double-blind randomized trial in 19 patients undergoing cholecystectomy. Bupivacaine (2 mg/kg) was dissolved in 300 ml isotonic saline and administered into the peritoneal cavity 10 min before the operation (n = 9). Saline was administered in a comparable group of patients (n = 10). There were no significant differences in pain scores between the groups during the first day after surgery (P greater than 0.05). Postoperative requirements of pethidine during the first 2 days after surgery did not differ significantly between the groups. Blood glucose levels were significantly lower in the bupivacaine-treated group 1 h (P less than 0.05) and 4 h (P less than 0.05) after skin incision. No significant differences were observed between the groups regarding plasma catecholamine and serum cortisol levels during and after surgery. Differences between the groups regarding urine output of catecholamines during the first and second postoperative days were not significant. Our results suggest that single administration of a local anesthetic intraperitoneally does not reduce pain or the sympathoadrenal response to upper abdominal surgery.

Adrenal Medulla↗
PubMed1988

Atrial natriuretic peptide during acute treatment of congestive heart failure.

Atrial natriuretic peptide (ANP) induces potent diuretic/natriuretic, vasorelaxing and aldosterone inhibitory effects. Increased plasma levels in congestive heart failure (CHF) have been reported. The aim of this study was to investigate plasma immunoreactive ANP (ir-ANP) levels during acute treatment of CHF. Seven patients with CHF underwent cardiac catheterization. Ir-ANP plasma levels were followed up to two h after administration of an orally given phosphodiesterase inhibitor (Milrinone); a substance with positive inotropic and peripheral vasodilating properties. In all patients cardiac output increased and cardiac filling pressures decreased markedly. Initially high ir-ANP plasma levels decreased. Our patients did not have an increased blood volume. It is concluded that plasma ir-ANP levels in the pulmonary artery rapidly decrease when atrial pressure is reduced. These data suggest that atrial pressure is the major determinant for release of ir-ANP in man and that the ability to respond quickly to changes in cardiac filling pressures is maintained in patients with severe CHF. Plasma ir-ANP levels may also become useful as an index of the degree of heart failure and serve as a tool in monitoring response to drug therapy.

Adult↗
PubMed1988

Baroreflex modulation of sympathetic activity and sympathetic neurotransmitters in humans.

We raised and lowered arterial pressures with stepwise intravenous infusions of phenylephrine and nitroprusside in ten healthy young men and measured changes of R-R intervals, post-ganglionic peroneal nerve muscle sympathetic activity, and antecubital vein plasma noradrenaline and neuropeptide Y concentrations. Respiratory peak-valley R-R interval changes declined with arterial pressure reductions, but did not rise with pressure elevations. Sympathetic activity was modulated by respiration over the entire range of pressures and, at each pressure, was more prominent in expiration than inspiration. Levels of muscle sympathetic nerve activity were low during supine rest, were suppressed almost completely during small increases of pressure, and were increased proportionally during pressure reductions. Over a range of average diastolic pressures from 69 to 89 mmHg, antecubital vein plasma noradrenaline levels were related linearly (r = 0.86, P = 0.0001) to muscle sympathetic nerve activity. Neuropeptide Y levels increased proportionally with muscle sympathetic nerve activity during pressure reductions, but did not decline during pressure elevations. Our results suggest that in man, muscle sympathetic outflow is modulated finely by small changes of baroreceptor input, and that during pharmacologically induced changes of arterial pressure, changes of antecubital vein plasma noradrenaline concentrations provide excellent estimates of changes of sympathetic nerve traffic to skeletal muscle.

Adult↗
PubMed1988

Haemodynamics and plasma ANP (atrial natriuretic peptide) after acute blood volume expansion in normotensive and spontaneously hypertensive rats.

Atrial natriuretic peptide (ANP) was measured in plasma during acute volume load in conscious, spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. During basal conditions immunoreactive ANP were similar in the SHR (630 +/- 56 pmoles l-1) and the WKY (657 +/- 114 pmoles l-1) groups. An acute 10% and 20% whole blood volume expansion resulted in a linear increase in immunoreactive plasma ANP in the WKY. In the SHR the increase in plasma ANP was attenuated during the 20% volume load. During the 10% and 20% volume load central venous pressure (CVP), central blood volume (CBV) and cardiac output increased relatively more in the SHR compared with the WKY group. In contrast, the increase in peripheral blood volume (PBV) and decrease in heart rate (HR) was attenuated in the SH rats. In the SHR group there was a shift of the ANP vs. CVP and ANP vs. CBV curves to the right compared with the WKY. We conclude that acute volume loading is a potent stimulus for ANP release in WKY as well as SHR. However, in the SHR, ANP release was blunted in spite of the increased centralization of the volume load in this rat strain. Thus, the decreased responsiveness of the ANP hormonal system may contribute to the development and maintenance of hypertension in this genetic form of hypertension.

Animals↗
PubMed1988

Differential haemodynamic effects of atrial natriuretic peptide (ANP) in normotensive and spontaneously hypertensive rats.

Central haemodynamic parameters and cardiac performance were measured in conscious spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto (WKY) control rats after a 10-min infusion of rat ANP (103-125), 1 micrograms kg-1 min-1. Mean Arterial blood pressure (MAP) decreased by approximately 10% in both groups of rats. Heart rate (HR) increased slightly in both strains during the infusion. In the normotensive group the fall in MAP was due to a reduction in cardiac output (CO) while in the SHR there was a decrease in CO as well as in total peripheral resistance (TPR). The ANP infusion also reduced central blood volume (CBV) and stroke volume (SV) in both groups of rats. The reduction in CBV and CO was significantly more pronounced in the WKY strain. Left ventricular end diastolic pressure (LVEDP) and cardiac contractility (dP/dt) did not change while central venous pressure (CVP) was slightly decreased in the WKY group as a result of the ANP infusion. We conclude that ANP reduces MAP in normotensive animals by a reduction in CO. In the SHR a reduction in TPR also contributes to the fall in MAP. Atrial natriuretic peptide did not exert any negative inotropic effects, but the reduction of CO was due to an increased venous compliance.

Animals↗
PubMed1988

Age-dependent effects of beta 2-adrenergic-stimulating drugs on fetal rabbit lung liquid and adrenal catecholamines.

The effects of the beta 2-adrenergic-stimulating drug, terbutaline, were studied on fetal rabbit lung liquid (FLL) at gestational ages between 25 and 30 days. At delivery terbutaline reduced FLL in rabbit fetuses with a gestational age of 26-30 days. The most pronounced reduction of FLL was seen at 28 days. Terbutaline administration reduced the wet lung weight/body weight (WLW/BW) ratio at delivery in the 28- and 30-day-old rabbit pups. In the 26-day-old animals, beta 2-adrenergic stimulation had no significant effect on the WLW/BW ratio and at 25 days of gestational age the ratio was increased. After parturition, however, the difference in WLW/BW between the terbutaline and control animals, seen at birth, was attenuated and, at 60 min of postnatal age, the difference was no longer observed. Terbutaline decreased the adrenal content of noradrenaline and adrenaline most marked at 28 days of gestational age, but did not alter the adrenaline/noradrenaline ratio. Furthermore, adrenal dopamine was decreased after terbutaline, suggesting a decreased catecholamine synthesis. Our data show that a positive effect of terbutaline on FLL in rabbit pups was most marked during late but not early gestational age. beta 2-Adrenergic treatment may, however, reduce adrenal catecholamines.

Adrenal Glands↗
PubMed1988

Effects of antenatal hydrocortisone on tidal volumes in spontaneously breathing preterm newborn rabbits. Possible mediation by adrenal catecholamines.

Rabbit fetuses were injected on day 26 of gestation with hydrocortisone (2 mg) and delivered by hysterotomy 2 days later. The animals were tracheotomized at birth, and tidal volumes and esophageal pressures were recorded during spontaneous ventilation at standardized intervals from the first breath to the age of 2 h. In a subgroup of animals, the catecholamine content was measured in the adrenal glands. In comparison with littermate controls, tidal volumes were enlarged in hydrocortisone-treated neonates at the first breath and 60 min after birth; however, this effect was associated with an increased incidence of intra-alveolar hemorrhage. Hydrocortisone-treated animals also had a significantly increased adrenal content of adrenaline. Our data confirm a modest beneficial effect of antenatal hydrocortisone treatment on the fetal lung and suggest that this might in part be mediated by adrenal catecholamines. Stimulation of beta-adrenergic receptors could thus potentiate the effect induced by direct influence of glucocorticoids on fetal lung maturation.

Adrenal Glands↗
PubMed1988

Plasma atrial natriuretic peptide (ANP) and maternal hemodynamic changes during normal pregnancy.

Peripheral venous plasma concentrations of immunoreactive atrial natriuretic peptide (irANP) were studied longitudinally in 12 women at the 12th, 24th, and 36th week of pregnancy as well as 3-5 days and 3 months post partum. Serial measurements of maternal hemodynamics were performed simultaneously with blood sampling for irANP determination. With advancing pregnancy there were significant increases (p less than 0.001) in cardiac output, stroke volume and heart rate, while total peripheral vascular resistance decreased (p less than 0.001). All these changes were normalized 3 months post partum. Plasma irANP increased (p less than 0.05) from 23.2 +/- 1.3 pM/l at week 12 to 25.9 +/- 1.5 pM/l at week 36 of pregnancy, and fell significantly (p less than 0.01) to 20.5 +/- 1.1 pM/l 3 months post partum. Changes in plasma irANP appear to be related to changes in maternal central hemodynamics. The changes in ANP release probably represent one of several mechanisms that maintain circulatory and volume homeostasis during normal pregnancy.

Adult↗
PubMed1988

Antihypertensive effects of ketanserin and ritanserin in the spontaneously hypertensive rat.

Acute as well as chronic treatment with ketanserin but not with ritanserin reduced the blood pressure in the spontaneously hypertensive rat, indicating that 5-HT2-receptor blockade alone does not have antihypertensive properties. Whereas the blood pressure reduction to acute administration of ketanserin was directly related to its ability to shift the dose-response curve of phenylephrine (alpha 1-adrenergic blockade), the same relationship was not apparent following chronic treatment with ketanserin. This suggests that the 5-HT2- and alpha 1-blockade may complement each other in reducing the blood pressure, a conclusion supported by the observation that in the conscious rat, 5-HT2-receptor blockade by ritanserin enhanced the hypotensive response to prazosin. However, ritanserin did not influence the ability of prazosin to antagonize pressor responses to phenylephrine in the pithed rat.

Animals↗
PubMed1988

Experience with ketanserin and ritanserin in hypertensive patients.

In patients with essential hypertension, ketanserin (40 mg once or twice daily) reduces the blood pressure in mono- and combination therapy. Despite evidence of peripheral vasodilation, the heart rate is reduced. This would suggest that ketanserin has an additional sympathoinhibitory effect. However, the influence of ketanserin on plasma catecholamine levels at rest and during exercise or stress was small, and to date there is little evidence for a central sympathoinhibitory effect of ketanserin in humans. The antihypertensive effects of ritanserin, a selective 5-HT2-receptor antagonist, were investigated in a double-blind, placebo-controlled crossover study (4 weeks). Treatment with ritanserin, 10 mg twice daily, was ineffective in hypertensive patients, which indirectly suggests that the 5-HT2-blocking properties of ketanserin cannot alone be responsible for its antihypertensive effects.

Antihypertensive Agents↗
PubMed1988

Are there reasons to believe that the antihypertensive effects of serotonin (S2) antagonists are age-related?

The potential age-dependent antihypertensive responses to serotonin antagonists are critically reviewed with regard to the following considerations: Are they beneficial to the patient? Are they related to age-dependent changes in pharmacokinetics or pharmacodynamics? Are they necessarily true? The paper is focused on ketanserin, which is the only major serotonin (S2) antagonist that has yet been used to any extent in patients. Based on the available data in the literature, we conclude that the age-related antihypertensive effect of ketanserin is a beneficial phenomenon since it does not seem to be paralleled by a corresponding increase in side effects. Furthermore, the mechanism seems to be due to changes in the pharmacodynamics of the drug on the platelet or vascular smooth muscle since there is only negligible alteration in pharmacokinetics occurring with advanced age. Although multiple independent trials or pooled data strongly indicate that the efficacy of ketanserin increases with age, not all investigators agree. In our opinion, the interindividual variation in drug response is more characteristic to the drug than the relationship to age. Therefore, the selection of patients for ketanserin therapy should be based on individual testing in addition to age grouping.

Aged↗
PubMed1988

Effects of sodium restriction and energy reduction on erythrocyte sodium transport in obese hypertensive men.

Twelve moderately obese middle-aged male out-patients with untreated mild hypertension reduced their sodium intake by about 120 mmol/day during 4-6 weeks. The low sodium diet period was followed by a period of energy reduction as well as sodium restriction for 15 weeks. Mean body mass was then reduced by 7.5 +/- 1.0 kg. Intraerythrocyte sodium (IeNa), sodium influx (Na-influx) and sodium efflux rate constant (Na-efflux rate), were measured before intervention, during salt restriction and during salt and energy restriction. Plasma renin activity (PRA) and urinary excretion of aldosterone (U-Aldo) and noradrenaline (U-NA) were also determined during the three observation periods. During sodium restriction there was a significant increase in PRA and U-Aldo, but no change was seen in IeNa, Na-influx or Na-efflux rate constant. During sodium restriction there was a significant positive correlation between PRA and both Na-influx and Na-efflux rate constant. When energy reduction was combined with sodium restriction, PRA and U-NA both diminished significantly. Na-influx and Na-efflux rate also exhibited a significant decrease while IeNa did not change. Sodium restriction caused a significant fall in mean arterial blood pressure and a tendency to a further decrease was seen when energy intake was also reduced. No significant correlation could be found between the fall in blood pressure and changes in cellular sodium transport. These data indicate that the renin-angiotensin-aldosterone system and sympathetic activity influence the regulation of erythrocyte sodium turnover during sodium and energy restriction in obese hypertensive men.

Biological Transport↗
PubMed1987

beta-Casomorphins induce apnea and irregular breathing in adult rats and newborn rabbits.

Bovine beta-casomorphin, beta-casomorphin, morphiceptin or morphine were administered systemically (i.v. or i.p.) and intracerebroventricularly (lateral or IVth ventricles) to anesthetized adult rats and preterm newborn rabbits. All agents caused dose-related depressions of respiratory frequency and tidal volume. Morphiceptin and beta-casomorphin were approximately equipotent to morphine while beta-casomorphin was 10 times as potent after intracerebroventricular injection. The beta-casomorphins decreased inspiratory drive and prolonged the expiratory phase by delaying the setpoint for inspiration. A respiratory depression could be elicited by systemic administration of morphiceptin but not by beta-casomorphin or beta-casomorphin. All ventilatory effects induced by the beta-casomorphins could be readily reversed or prevented by naloxone. Intracerebroventricular but not intraperitoneal injection of beta-casomorphin depressed ventilation in preterm newborn rabbits in a similar pattern with apnoic periods to that seen in the adult rats. In addition, an irregular breathing pattern was elicited. Thus, the bovine beta-casomorphins possess potent central respiratory depressive effects. However, after systemic administration, only morphiceptin which is more metabolically stable induced a shortlasting effect on ventilation in adult rats.

Amino Acid Sequence↗
PubMed1987

Pharmacokinetics of different epidural sites of morphine administration.

In order to determine the rate and degree of redistribution of morphine within the cerebrospinal fluid (CSF), and whether it was affected by the site of and volume of the injection, morphine was given to 23 elderly patients undergoing thoracotomy - in 10 ml saline in the lumbar epidural interspace (n = 5), in 10 ml saline in the thoracic epidural interspace (n = 5), in 2 ml saline in the thoracic interspace (n = 8) and in 10 ml saline in the lumbar epidural interspace (n = 5). The plasma concentration of morphine in all patients was comparable and was much lower than in the CSF. The CSF morphine concentration, measured as the area under the CSF concentration curve (AUC), the maximal CSF concentration (Cmax) and the time to reach maximal CSF concentration (tmax), varied between the four groups. The variation was related to the site of the injection; the AUC and Cmax were lower and tmax appeared later after thoracic than lumbar injection. Lumbar CSF morphine concentrations were further reduced by thoracic epidural injection of morphine in a small as compared to a large volume. The permeability of the dura to morphine was not influenced by the volume used. The results show that morphine is not homogeneously distributed within the CSF. The availability of morphine to CSF from the epidural space is not altered by the injection volume, but the drug remains more localized in CSF after epidural injection of morphine in a small volume.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗