PubMed Health⌕ Search

Biomedical subjects

J Hedner

Publications and source records attributed to J Hedner.

At least 19 recordsLinked to original sources
PubMed1999

Effect of serotonin uptake inhibition on breathing during sleep and daytime symptoms in obstructive sleep apnea.

Pharmacologic enhancement of serotonergic transmission by serotonin uptake inhibition has been suggested as one approach to improve upper-airway patency and thus nocturnal breathing in patients with obstructive sleep apnea (OSA). To test this hypothesis, we performed a double-blind, randomized, placebo-controlled crossover study testing the effect of paroxetine (20 mg od) on polysomnographic and psychopathologic outcomes in 20 male OSA patients (mean age 52.1 years, mean BMI 28.7 kg/m2, mean oxygen desaturation index on a previous screening 25.4/hour). The two treatment periods of 6 weeks and the separating washout period of 4 weeks were completed by 17 patients. Paroxetine reduced the apnea index during NREM sleep (-35%, p = 0.003), but not during REM sleep. No significant effect on hypopnea indices was found. With the exception of a previously described REM-postponing effect (p = 0.05), sleep architecture was not significantly influenced by paroxetine. Similarly, the effect of paroxetine on apnea was not associated with a significant overall alleviation of psychopathologic symptoms as rated on the Comprehensive Psychopathological Rating Scale or OSA-related daytime complaints assessed by visual analog scales. We conclude that enhanced serotonergic transmission improves breathing during NREM sleep in OSA. This effect is poorly related to effects on sleep architecture or daytime symptoms.

Adult↗
PubMed1999

An independent association between obstructive sleep apnoea and coronary artery disease.

Previous studies of sleep and breathing suggest an independent association between coronary artery disease (CAD) and obstructive sleep apnoea (OSA) in middle-aged males and females. These studies, however, were criticized because they did not properly adjust for all important confounding factors. In order to better control for the impact of these confounders, a case-control study was performed, matching for age, sex and body mass index (BMI), and additionally adjusting for hypertension, hypercholesterolemia, diabetes mellitus and current smoking. A consecutive selection of 62 patients (44 males and 18 females, mean age 69 yrs, range 44-88 yrs) requiring intensive care for angina pectoris or myocardial infarction at the County Hospital of Skaraborg, Skövde, Sweden, as well as 62 age-, sex- and BMI- matched control subjects without history or signs of heart disease underwent an overnight sleep/ventilatory monitoring study. The time interval between discharge from the intensive care unit and the overnight study ranged between 4 and 21 months. OSA, defined as a Respiratory Disturbance Index (RDI) of > or =10 x h(-1), was present in 19 CAD patients but only in eight control subjects (p=0.017). Using a univariate logistic regression analysis, current smoking (odds ratio (OR) 8.1, 95% confidence interval (CI) 2.2-29.0), diabetes mellitus (OR 4.2, 95% CI 1.1-16.1) and OSA (OR 3.0, 95% CI 1.2-7.5), but not hypertension (OR 1.5, 95% CI 0.7-3.2) and hypercholesterolaemia (OR 1.8, 95% CI 0.7-4.1) were significantly correlated with CAD. In a multiple logistic regression model, current smoking (OR 9.8, 95% CI 2.6-36.5), diabetes mellitus (OR 4.2, 95% CI 1.1-17.1) and OSA (OR 3.1, 95% CI 1.2-8.3) all remained independently associated with CAD. In summary, these data suggest a high occurrence of obstructive sleep apnoea in middle-aged and elderly patients with coronary artery disease requiring intensive care, which should be taken into account when considering risk factors for coronary artery disease.

Adult↗
PubMed1999

Plasma noradrenaline and neuropeptide-Y may not be of primary importance in the pathophysiology of cardiac involvement in systemic sclerosis.

OBJECTIVE: The present study was performed to measure concentrations of plasma noradrenaline and neuropeptide-Y-like immunoreactivity in relation to cardiac function in patients with systemic sclerosis (SSc). METHODS: Plasma noradrenaline was measured by high performance liquid chromatography and neuropeptide-Y by radioimmunoassay in 30 consecutive patients with SSc and 48 sex and age matched controls. Left ventricular (LV) function was evaluated by Echocardiography. RESULTS: There were no significant differences between patients and controls in either plasma noradrenaline or plasma neuropeptide-Y. LV dysfunction and hypertrophy were common among patients. Plasma Neuropeptide-Y was related only to systolic function, while noradrenaline was related to both systolic and diastolic function as well as to LV hypertrophy. CONCLUSION: Patients with SSc develop different forms of myocardial dysfunction without activation of the sympathetic nervous system as evaluated by plasma noradrenaline and neuropeptide-Y; leaving vascular disease of the heart to be a main candidate.

Adult↗
PubMed1997

Endothelin may be pathogenic in systemic sclerosis of the heart.

We evaluated 30 consecutive patients and 48 age- and sex-matched controls to explore the possibility of a pathogenic contribution by plasma endothelin-1 in the cardiac expression of systemic sclerosis. Venous plasma endothelin-1 was measured by radio-immunoassay and left ventricular function by echocardiography. The patient group had elevated plasma endothelin-1 (2.6 +/- 0.2 vs. 1.8 +/- 0.1 pmol/1, P < 0.001), but endothelin-1 was not related to age, heart rate, blood pressure, total peripheral resistance, disease duration or systemic sclerosis score. Endothelin-1 was related to left ventricular hypertrophy in terms of septal thickness (r = 0.33, P < 0.01) and left ventricular mass index (r = 0.32, P < 0.01). Plasma endothelin-1 was further related to measures indicating reduced left ventricular filling; left atrial emptying index (r = -0.50, P < 0.0005), the first third filling fraction (r = -0.31, P < 0.05) and the time velocity integral of Doppler early/late filling velocity (r = -0.40, P < 0.001). Furthermore, circulating endothelin-1 was related to impaired left ventricular contractility as estimated by pre-ejection period/left ventricular ejection time (r = 0.32, P < 0.01) and end-systolic wall stress/volume index (r = -0.30, P < 0.05). We conclude that plasma endothelin-1 is elevated in relation to the degree of left ventricular hypertrophy, diastolic dysfunction and impaired contractility in systemic sclerosis. It may be of pathogenic importance to the cardiac involvement in systemic sclerosis which is not mediated via an increase in systemic blood pressure. It is not yet clear whether our findings are exclusive to systemic sclerosis patients or represent a generalized phenomenon in patients with impaired left ventricular function.

Adult↗
PubMed1997

The lack of respiratory effects of the ocular hypotensive drug latanoprost in patients with moderate-steroid treated asthma.

The use of beta blockers for glaucoma treatment may cause serious bronchoconstriction in patients with chronic obstructive pulmonary disease. The synthetic prostaglandin (PG) F2 alpha-analogue latanoprost (13,14,dihydro-17-phenyl-18,19,20-trinor-PGF-2-alpha-iso propylester) represents a new class of drugs for glaucoma treatment. In this study the pulmonary tolerability to latanoprost in 12 healthy volunteers and 11 (one withdrawal due to a sty before latanoprost treatment) subjects with moderate but stable steroid-treated intrinsic asthma was examined. Asthmatic subjects received 30 microliters of vehicle (placebo) at the scheduled administration times on baseline day. On a second day, a minimum of one week later, increasing concentrations (0.35, 115 and 350 micrograms/ml) of latanoprost were added to the vehicle and given topically to both eyes. Healthy volunteers were given latanoprost only. ECG, blood pressure, heart rate, forced expiratory volume (FEV1), peak expiratory outflow (PEF) and forced vital capacity (FVC) were recorded immediately prior to and 15, 30, 45 and 60 minutes after latanoprost. Asthmatic patients inhaled salbutamol (0.2 mg) at 60 minutes after the highest latanoprost dose. There were no significant differences in pulmonary function, blood pressure or heart rate after latanoprost in the healthy volunteers. Moreover, all parameters were unaffected in asthmatic patients on the day latanoprost was given compared to the baseline day. Latanoprost did not dampen the bronchodilator response to beta-2-adrenergic stimulation. It is concluded that latanoprost did not affect lung function in healthy subjects or in asthmatics after a total accumulated dose 10 times that clinically recommended for glaucoma treatment. Therefore, latanoprost appears to be safe for glaucoma treatment in patients with steroid-treated stable moderate intrinsic asthma.

Administration, Inhalation↗
PubMed1997

Reduced hospitalization with cardiovascular and pulmonary disease in obstructive sleep apnea patients on nasal CPAP treatment.

Cardiovascular and pulmonary disease (CVPD) is common in patients with obstructive sleep apnea syndrome (OSAS). This retrospective study addressed the accumulated in-hospital time during 2 years prior to treatment with nasal continuous positive airway pressure (nCPAP) as compared to 2 years after initiating of nCPAP in patients with OSAS and CVPD. A cohort representing all patients (n = 88) receiving nCPAP during the period 1988-1994 at the Skövde Central Hospital, Skövde, Sweden, was studied. Data collection was based on interviews with patients as well as reviews of clinic charts. All hospitalizations and diagnostic codes by any type were thereby successfully gathered for the whole group. Six patients with confounding serious diseases were excluded from the analysis. A CVPD diagnosis (ICD-9, codes 401-435 and 490-496) was found in 54 out of 82 patients (66%), of whom 36 of 58 were nCPAP users (62%) and 18 of 24 were nonusers (75%). In 54 sleep apneics with CVPD, 31 were hospitalized acutely under one or more of these diagnostic codes during the study period of 4 years. The total number of in-hospital days due to CVPD in the nCPAP users (n = 19) before nCPAP prescription was 413 days (median 10, range 3-66) compared to 54 days (median 0, range 0-25) after nCPAP (p < 0.0001). The corresponding values for the nonuser group (n = 12) was 137 days (median 8.5, range 0-42) before and 188 days (median 9.5, range 0-47) after the nCPAP prescription (ns). We conclude that nCPAP treatment reduces the need for acute hospital admission due to CVPD in patients with OSAS. This reduction of concomitant health care consumption should be taken into consideration when assessing the cost-benefit evaluation of nCPAP therapy.

Aged↗
PubMed1997

Differences in bronchodilating potency of salbutamol in Turbuhaler as compared with a pressurized metered-dose inhaler formulation in patients with reversible airway obstruction.

Two studies are presented, with the aim of establishing the dose potency ratio for salbutamol given via Turbuhaler and via a pressurized metered-dose inhaler (pMDI). Both studies were of a double-blind, randomized design. Outpatients with mild-to-moderate chronic reversible airway obstruction were given single doses of salbutamol administered via Turbuhaler and via pMDI. Efficacy and safety variables were measured before and during 6 h after each dose. The first study was a four-way crossover study including 12 patients. The salbutamol doses given were: 50, 100 and 2x100 microg via Turbuhaler and 2x100 microg via pMDI (Ventolin). The study showed that 2x100 microg of salbutamol inhaled via Turbuhaler is more potent than 2x100 microg salbutamol inhaled via a pMDI, and that 100 microg salbutamol via Turbuhaler is at least as potent as 2x100 microg salbutamol inhaled via a pMDI. The second study including 50 patients was a placebo-controlled five-way crossover, study. Two doses of salbutamol via Turbuhaler, 50 and 2x100 microg, and via pMDI, 100 and 2x200 microg, were given. There was a dose-dependent response in forced expiratory volume in one second (FEV1) for both inhalers. Adjusted for differences in baseline FEV1 values, the estimated relative dose potency for Turbuhaler versus pMDI was 1.98:1 (95% confidence interval 12-3.2). These studies showed that the same bronchodilating effect can be achieved when half the dose of salbutamol given via a conventional pressurized metered-dose inhaler is given via Turbuhaler.

Administration, Inhalation↗
PubMed1996

Haemodynamic effects and pharmacokinetics of oral d- and l-nebivolol in hypertensive patients.

OBJECTIVE: Nebivolol is a selective beta 1-adrenergic receptor blocker possessing an ancillary vasodilating effect. The objective of the present study was to study the haemodynamic and pharmacokinetic properties of nebivolol 5 mg once daily in a double-blind, placebo-controlled cross-over study. METHODS: Fifteen patients, 12 men and 3 women, with essential hypertension were investigated. Blood pressure and peripheral circulation were determined after acute oral nebivolol administration, 5 mg daily, and after 4 weeks treatment. RESULTS: The acute effect on blood pressure upon single-dosing was weak and non-significant. After 4 weeks both systolic blood pressure (152 vs 163 mmHg) and diastolic blood pressure (89 vs 97 mmHg) were significantly reduced after nebivolol treatment as compared to placebo. Following the first dose the venous volume was higher on placebo (5.88 ml.100 ml-1 tissue) as compared to active nebivolol treatment (5.17 ml.100 ml-1 tissue), while there were no statistically significant differences with regard to venous plethysmographic findings after 1 month on placebo (5.53 ml.100 ml-1 tissue) or on active treatment (5.97 ml.100 ml-1 tissue). Calculated peripheral resistance did not differ between active treatment (617 units) or placebo (548 units) after the first dose, whereas it was significantly lowered after 4 weeks of nebivolol treatment (483 units) as compared to placebo (593 units). CONCLUSIONS: Oral nebivolol 5 mg once daily lowered blood pressure and heart rate during steady state compared to placebo. Moreover, venous volume was reduced during acute but not steady-state dosing, while peripheral resistance was unaffected in the acute phase but reduced during steady state. Plasma concentrations of the separate enantiomers plus hydroxylated metabolites after the first and last dose in hypertensive patients were similar to those in healthy subjects.

Adrenergic beta-Antagonists↗
PubMed1996

Substance P-induced respiratory excitation is blunted by delta-receptor specific opioids in the rat medulla oblongata.

The effects of substance P (SP) and the naturally occurring met-enkephalin and the synthetic mu-specific opioid agonist, DAGO (Tyr-D-Ala-Gly-N-Methy-Phe-Gly-ol) and the delta-specific opioid agonist DADL (Tyr-D-Ala-Gly-Phe-D-Leu) on basal ventilation were investigated in halothane-anaesthetized rats. Local injections of SP (0.75-1.5 nmol) in the ventrolateral medulla oblongata (VLM), e.g. nucleus paragigantocellularis, and nucleus reticularis lateralis increased ventilation because of an elevation of tidal volume. Met-enkephalin induced a short-lasting ventilatory depression mainly because of a depression of tidal volume. Activation of delta- and mu-opioid receptors in the VLM by local application of DADL and DAGO, respectively, induced ventilatory depression, which was later in onset and more long-lasting. Local administration of met-enkephalin into the VLM also produced a long-lasting inhibition of the SP-induced ventilatory excitation. A similar blockade of the SP-induced excitatory ventilatory response could be elicited by DADL but not by DAGO. This antagonistic effect was attenuated by local application of the delta-opioid receptor antagonist ICI 154. 129. We conclude that the naturally occurring met-enkephalin as well as synthetic mu- and delta-specific enkephalin analogues (DAGO and DADL, respectively) in VLM depress basal ventilation by an effect on inspiratory drive. There is a functional antagonism between activation of delta-opioid receptors and SP receptors into the VLM in respect to respiratory regulation.

Analgesics, Opioid↗
PubMed1996

A double-blind, randomized trial of sabeluzole--a putative glutamate antagonist--in obstructive sleep apnea.

The effect of sabeluzole (SAB), an agent with anti-excitatory amino acid activity, on sleep, breathing and daytime symptoms was investigated in 13 patients with obstructive sleep apnea (OSA). There was marked interindividual variation in both the effect on sleep and breathing and the plasma concentration of SAB. However, individual plasma drug concentration was highly correlated (r = 0.82, p = 0.02) with a reduction of the oxygen desaturation index during sleep (ODI) after treatment with SAB. Further investigation of this and agents of this type are warranted in patients with OSA.

Adult↗
PubMed1996

Vascular function in OSA.

A number of pathophysiological phenomena linked to sleep disordered breathing are likely to affect vascular function. This report briefly reviews current knowledge regarding neurogenic vascular tone and a number of circulating hormones with vascular actions in obstructive sleep apnea (OSA). New evidence suggesting a role of the vascular endothelium in the development of vascular disease in OSA is also presented.

Aldosterone↗
PubMed1996

Energy expenditure in obstructive sleep apnea: effects of treatment with continuous positive airway pressure.

We examined 24-h energy expenditure (EE) in a chamber for indirect calorimetry in five male patients with obstructive sleep apnea (OSA) and six snoring control subjects (snorers). The 24-h EE was remeasured in patients with OSA after 3-mo treatment with nasal continuous positive airway pressure (CPAP). Patients with OSA had a greater degree of severe sleep-breathing disturbance than snorers. Patients with OSA had higher 24-h EE [39.2 +/- 3.0 vs. 33.9 +/- 2.7 kcal.24 h-1.kg fat-free mass (FFM)-1, P < 0.05], daytime urinary norepinephrine and vanillylmandelic acid (VMA), and aminoterminal procollagen III peptide (PIIIp) levels, and they tended to have higher sleeping EE (32.4 +/- 4.1 vs. 26.3 +/- 1.9 kcal.24 h-1.kg FFM-1, P < 0.1) than snorers. CPAP treatment normalized sleep architecture and breathing. CPAP treatment also decreased sleep EE (from 32.4 +/- 4.1 to 27.2 +/- 1.4 kcal.24 h-1.kg FFM-1, P < 0.05) and EE variability during sleep (from 1.6 +/- 0.5 to 1.0 +/- 0.5 kcal.24 h-1.kg FFM-1, P < 0.05) and increased the basal metabolic rate-to-sleep EE ratio in all subjects. Serum PIIIp and plasma norepinephrine decreased after CPAP in all patients. We conclude that OSA is associated with an increased sleep EE, which is normalized by treatment with CPAP.

Adult↗
PubMed1996

Role of the autonomic nervous system in the acute blood pressure elevation during repetitive hypoxic and hypercapnic breathing in rats.

Acute intermittent repetitive hypoxia simulating sleep apnoea syndrome is responsible for acute rises in blood pressure (BP). In the rat, the BP rises are enhanced by added hypercapnia. To investigate the role of the autonomic nervous system (ANS) in acute hypertension during repetitive hypoxia alone, FiO2 (inspiratory fractional concentration of oxygen) 2 to 5%, or combined with hypercapnia FiCO2 (inspiratory fractional concentration of carbon dioxide) 2 to 5%, we used autonomic blockade by atropine (1 mg kg-1) + propranolol (1 mg kg-1)-phentolamine (1 mg kg-1). Seven Wistar male rats were chronically instrumented with two aortic and venous catheters. Repetitive administration of N2 and N2 + CO2 for 10s followed by 20s compressed air was repeated for 4-5 min before (control) and after autonomic blockade. After autonomic blockade there was no significant difference in mean blood pressure (MBP) during severe hypoxia (SHO) (14.9 +/- 0.5 mmHg) compared to control (10.5 +/- 0.9 mmHg), while MBP was significantly decreased in severe hypoxia + hypercapnia (SHOHC) (14.1 +/- 0.4 mmHg) compared to control (26.8 +/- 0.3 mmHg) (p < 0.001). We conclude that the acute BP rise observed during hypoxic breathing is not due to the activation of ANS, but when hypercapnia is added to the hypoxic stimulus about half of pressor response is caused by ANS.

Animals↗
PubMed1996

Nonsteroidal antiinflammatory drug modulation of behavioral responses to intrathecal N-methyl-D-aspartate, but not to substance P and amino-methyl-isoxazole-propionic acid in the rat.

Antinociception by nonsteroidal antiinflammatory drugs, notably diclofenac and S(+)-ibuprofen, has traditionally been attributed to peripheral tissue cyclooxygenase inhibition. This study investigates the potential role of the nitric oxide system for the central antinociceptive effects of diclofenac, S(+)-, and R(-)-ibuprofen. Diclofenac and S(+)- but not R(-)-ibuprofen inhibited the behavioral response dose dependently, "biting, scratching, and licking (BSL)," induced by the spinal application of N-methyl-D-aspartate, but not that of amino-methylisoxazole-propionic acid or substance P. Diclofenac and S(+)-ibuprofen induced a parallel shift in the number of BSL responses and in the duration of the response in the behavioral model at their approximate median effective doses (diclofenac 1 mumol and S(+)-ibuprofen 5 mumol). Pretreatment with L-arginine, the natural substrate for the nitric oxide synthetase, antagonized diclofenac, and S(+)-ibuprofen-induced suppression of the biting, scratching, and licking response evoked by intrathecal N-methyl-D-aspartate. D-arginine did not antagonize the diclofenac- and S(+)-ibuprofen-induced antinociception. The study results indicate that analgesia after diclofenac and S(+)-ibuprofen involves a central mechanism which may add to the peripheral antinociceptive effect of these agents. The central action of diclofenac and S(+)-ibuprofen is partly mediated by an interaction with the N-methyl-D-aspartate receptor and nitric oxide-generating mechanisms.

Animals↗
PubMed1995

Reduction in sympathetic activity after long-term CPAP treatment in sleep apnoea: cardiovascular implications.

Twelve patients with severe obstructive sleep apnoea were included in an open, long-term, prospective, follow-up study addressing the effects of nasal continuous positive airway pressure (CPAP) on sympathetic activity, cardiac structure and blood pressure. Plasma norepinephrine (P-NE) (daytime at rest), daytime and night-time urinary excretion of NE (U-NE), vanylmandelic acid and metanephrines, together with 24 h noninvasive blood pressure (BP) recording and Doppler-echocardiography, were assessed before and after a mean of 20.5 (range 14-26) months of CPAP. Average self-reported use of CPAP was 89% (range 65-100%) of time spent in bed. Resting daytime P-NE ranged 0.35-0.83 ng.ml-1, which is elevated compared to healthy controls. Only night-time U-NE, mean daytime BP and average 24 h BP were related to severity of OSA. Night-time metanephrine was related to daytime and night-time diastolic, as well as night-time systolic, BP. Left ventricular mass index (LVMI) at baseline was correlated to daytime systolic BP and P-NE. Long-term CPAP treatment reduced biochemical markers of sympathetic activity. P-NE decreased by approximately 50%, and daytime and night-time vanylmandelic acid and metanephrine by 32-54%. In contrast, there were no overall reductions in BP or LVMI. It is concluded that obstructive sleep apnoea is associated with high sympathetic activity both during sleep and waking periods. Urinary metanephrine excretion seemed to reflect blood pressure, but neither daytime nor night-time catecholamine excretion was directly related to disease severity in patients with severe obstructive sleep apnoea.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure↗