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Biomedical subjects

J Hedner

Publications and source records attributed to J Hedner.

At least 55 records · Page 3Linked to original sources
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

Daytime waking autonomic function and vascular control in OSA.

This paper deals with the potential role of two blood pressure regulatory systems in the development of hypertension in obstructive sleep apnoea (OSA). Beside the acute and long-term sympathoexcitation documented in this disease, there seems to be an impaired endothelium-dependent vascular relaxation. In particular, nitric oxide (NO)-mediated vasodilatation was impaired in patients with OSA. Both these changes act to increase blood pressure during physiological conditions. However, they may not be determinants for hypertension development in OSA as no differences between normo- and hypertensive patients with OSA were detected. Nevertheless, an altered balance between the vasoconstrictive influence of the sympathoadrenergic system and the vasodilatory action of NO-dependent vascular relaxation may be of importance in the development of sustained hypertension in OSA.

Journal Article↗
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↗
PubMed1995

Impact of obstructive sleep apnea and sleepiness on metabolic and cardiovascular risk factors in the Swedish Obese Subjects (SOS) Study.

OBJECTIVE: To determine if obstructive sleep apnea (OSA) is independently associated with cardiovascular risk factors and health status in subjects with severe obesity. DESIGN: Cross-sectional analysis of epidemiological data. SUBJECTS: 3034 participants in the Swedish Obese Subjects (SOS) Cohort. Two sub-groups with a high and low likelihood for OSA based on questionnaire data were analysed in detail. MEASUREMENTS: General health questionnaires, anthropometric data including CT calibrated values for body fat distribution and lean body mass, blood pressure, fasting insulin, triglycerides, cholesterol, uric acid, glucose. RESULTS: Self-reported loud snoring and observed breathing pauses (high likelihood of OSA) was associated with increased frequency of WHO Grade 4 dyspnea, admissions to hospital with chest pain, myocardial infarction, blood pressure, fasting insulin, fasting triglyceride (women only), uric acid (women only) after adjustment for body fat distribution and other potential confounders. CONCLUSION: OSA may be another medical disorder which contributes to morbidity in severe obesity and is associated with some of the components of the metabolic syndrome observed in the centrally obese.

Adult↗
PubMed1994

Atrial natriuretic peptide and its relation to cardiac dimensions and function in patients with systemic sclerosis.

OBJECTIVES: Were to determine whether plasma atrial natriuretic peptide (ANP) is increased in patients with systemic sclerosis (SScl) and to evaluate its relation to cardiac dimensions and function. METHODS: Using radio-immunoassay, plasma ANP was determined in 30 patients with SScl and 48 age and sex matched controls. The plasma ANP level was related to cardiac structure and function as determined by two-dimensional echocardiography (2-D echo). RESULTS: Plasma ANP was markedly elevated among patients as compared to controls (239,4 +/- 59 vs 178.2 +/- 36 pmpl/l, p < 0.0005). The left atrial long-axis and area were increased, and ANP was directly related to both measurements (r = 0.27, p < 0.05 and r = 0.40, p < 0.005, respectively). Plasma ANP was also related to the increased right atrial long-axis (r = 0.27, p < 0.05). The ANP level was not related to LV systolic function as estimated by ejection fraction, fractional area change and end-systolic wall stress, neither did these measures differ between patients and controls. However, there was an inverse correlation between ANP level and stroke volume (r = -0.35, p < 0.05), which was lower among the patients (p < 0.005). ANP displayed also an inverse relation to LV long axis diameter (r = -0.37, p < 0.005) and area (r = -0.42, p < 0.005) as well as to LV end-diastolic volume (r = -0.42, p < 0.005). Various measurements indicated LV hypertrophy among the SScl patients in spite of a small LV cavity. ANP was directly related to measures of LV hypertrophy, as interventricular septum thickness (r = 0.44, p < 0.005), LV posterior wall thickness (r = 0.34, p < 0.05), the wall thickness to cavity dimension ratio (r = 0.36, p < 0.05), and LV myocardial area (r = 0.36, p < 0.05). There was no relationship between ANP concentration and heart rate, blood pressure or total peripheral resistance. CONCLUSION: These results suggest that the ANP production is not reduced in SScl. Rather, circulating ANP is elevated in relation to the degree of LV hypertrophy. This implies that ANP may be useful for the identification of cardiac involvement in patients with SScl.

Adult↗
PubMed1994

Atrial natriuretic peptide: relation to left ventricular filling properties in patients with systemic sclerosis.

To determine the relation between left ventricular filling properties and plasma atrial natriuretic peptide in systemic sclerosis, we evaluated 30 consecutive patients and 48 age- and sex-matched controls. The venous plasma atrial natriuretic peptide was measured by radio-immunoassay. Left ventricular involvement was evaluated by echocardiography and mitral regurgitation was evaluated by Doppler. The patient group had markedly elevated plasma atrial natriuretic peptide as compared to the matched controls, (239.4 +/- 59 vs. 178.2 +/- 36 pmol/l, P < 0.0005). We found signs of impaired left ventricular filling properties among the patients with an increase of the Doppler A-wave velocity and A/E ratio. A relative reduction of early filling was found in spite of some degree of mitral regurgitation in two-thirds of the patients. The plasma atrial natriuretic peptide concentration was related to the A-wave velocity (r = 0.44, P < 0.0005), the A/E ratio (r = 0.40, P < 0.005), and also to the degree of mitral regurgitation (r = 0.43, P < 0.005). The relationship to the A-wave velocity remained when considering possible confounding factors. We conclude that the previously observed fibrotic process in systemic sclerosis does not prevent production and liberation of plasma atrial natriuretic peptide in relation to factors distending the left atrium, such as altered left ventricular filling properties and the presence of mitral regurgitation. However, the moderate relationships between atrial natriuretic peptide and haemodynamic variables indicate that the peptide might also be an independent indicator of cardiac involvement in systemic sclerosis.

Adult↗
PubMed1994

Acetaminophen blocks spinal hyperalgesia induced by NMDA and substance P.

The hypothesis tested was that inhibition of the L-arginine-nitric oxide (NO) pathway may represent a potential central mechanism of action for acetaminophen (paracetamol). Spinal administration of N-methyl-D-aspartate (NMDA, 0.5 nmol), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA, 0.1 nmol) or substance P (SP, 0.5 nmol) to the rat provoked a specific behaviour characterized by biting, scratching and licking (BSL). This behaviour was antagonized by pretreatment with acetaminophen for NMDA and SP but not for AMPA. Further, the antinociceptive effect of acetaminophen was readily reversed by administration of the natural substrate for nitric oxide synthase (NOS), L-arginine, but not by D-arginine. This suggests that the analgesic effect of acetaminophen is related to inhibition of NO generation. Potential mechanisms for this may involve NMDA and SP. Our data suggest that a significant portion of the analgesic effect of acetaminophen, when used clinically, may be related to an interaction with the central nervous system L-arginine-NO pathway.

Acetaminophen↗
PubMed1994

Relationship between chemosensitivity, obesity and blood pressure in obstructive sleep apnoea.

It has previously been documented that patients with obstructive sleep apnoea (OSA) have an abnormal blood pressure (pressor) response to acute hypoxia when awake. The relationship between hypoxic chemosensitivity and 24 h blood pressure in OSA is not known. Twenty-four hour ambulatory BP (ABP) was measured at 15 min intervals for 24 h using a non-invasive device (Oxford Medilog ABP or Spacelabs 90207 recorder) in 49 men (mean age 51 +/- 9 years), with OSA. The BP response to acute hypoxia was measured either directly (radial arterial line) or indirectly (Finapress) during wakefulness. The pressor response to hypoxia (expressed as the slope of the regression line of mean BP on % fall in arterial oxygen saturation) was compared with the results of the ABP recording, sleep study data and clinical variables. A pressor response to acute hypoxia was present in all patients (mean 1.4 +/- 1.1 mmHg/% delta SaO2, range 0.1-4.5). There was a relationship between the magnitude of the pressor response to hypoxia, severity of sleep apnoea (RDI and minimum SaO2) and central obesity (waist measurement). In contrast, there was no relationship between BP response to hypoxia during wakefulness and 24-h BP. However, increasing obesity and severity of OSA were associated with loss of the normal fall in BP at night. We conclude that enhanced chemosensitivity is common in OSA but there is no demonstrable link between chemosensitivity and mean daytime or night-time ABP.

Acute Disease↗
PubMed1994

Nitrazepam in patients with sleep apnoea: a double-blind placebo-controlled study.

We wanted to assess whether benzodiazepines worsen sleep apnoea, since their use in such patients has been controversial. Fourteen male patients with mild to moderate obstructive sleep apnoea were investigated in a placebo-controlled, double-blind study evaluating the influence of nitrazepam (NIT) on apnoea frequency and severity. Each patient was given oral nitrazepam 5 or 10 mg, or corresponding placebo, in a randomized order on three separate nights. Wash-out time was one week. A complete sleep study was undertaken at each study night. Eleven patients completed the study. Although there were individuals with marked variability in apnoea index between the three study nights, there was no significant change in apnoea index or minimum arterial oxygen saturation with any of the two nitrazepam dosages studied. Only 3 out of 11 patients had a higher apnoea index after both nitrazepam doses compared to placebo, and in these patients the increase in sleep-disordered breathing was of marginal clinical significance. Nitrazepam caused a modest increase in total sleep time and a decrease in rapid eye movement (REM) sleep. These results demonstrate that nitrazepam does not worsen sleep apnoea in patients with mild to moderate sleep apnoea. The previously reported sleep apnoea promoting effects of benzodiazepines may be restricted to a small subgroup of patients with sleep-disordered breathing.

Contraindications↗
PubMed1993

Morphine-sparing effect of diclofenac in cancer pain.

The effectiveness of diclofenac 50 mg t.i.d. as additive treatment to parenteral patient-controlled administration therapy (PCAT) with morphine in cancer pain has been investigated in a double-blind study. In the fifteen patients who completed the study, morphine i.v. was titrated to optimal pain relief over 5 days. The mean total morphine consumption was significantly reduced during diclofenac administration (82.8 mg morphine per day) compared to placebo (95.0 mg morphine per day). The reduction in mean morphine consumption during active treatment with diclofenac was independent of the initial dose of self-titrated morphine. Pain, self-assessed according to VAS, tended to be lower during the diclofenac period, although the difference did not reach statistical significance. No adverse events were recorded among the 15 patients who completed the study. The present findings show that a non-steroidal anti-inflammatory agent, such as diclofenac, has a morphine-sparing effect in morphine-treated patients with cancer pain.

Adult↗
PubMed1993

Atrial peptides, ANP(1-98) and ANP(99-126) in health and disease in an elderly population.

Circulating immunoreactive atrial natriuretic peptide, IrANP(99-126) and the N-terminal fragment of the prohormone, IrANP(1-98) were measured in two population samples from the general population of Gothenburg, Sweden. A group of 85-year olds (974 subjects) and a group of 40-year olds (191 subjects) were investigated in respect of cardiovascular, renal and metabolic disease. IrANP(99-126) and IrANP(1-98) were significantly higher in the 85-year olds compared to the 40-year olds, and were significantly increased in subjects with congestive heart failure, ischaemic heart disease, atrial fibrillation and renal dysfunction but not in subjects with hypertension. Eighty-five-year-old subjects who were on treatment with digitalis, beta-adrenergic-blockers, nitrates and diuretics had significantly increased IrANP(99-126) and IrANP(1-98). In multivariate analysis IrANP(99-126) concentrations were predictive for congestive heart failure, ischaemic heart disease, atrial fibrillation and treatment with beta-blockers and anti-depressant drugs. IrANP(1-98) was predictive for congestive heart failure, ischaemic heart disease, atrial fibrillation, diabetes mellitus, renal failure and drug treatment with beta-blockers and neuroleptics. We conclude that measurements of circulating concentrations of IrANP(99-126) and/or IrANP(1-98) may add valuable information in the diagnosis of congestive heart failure and ischaemic heart disease in an elderly population. It remains to be determined whether routine measurements of circulating IrANP (99-126) and IrANP(1-98) may be of value in predicting current cardiovascular disease for the individual patient.

Adult↗
PubMed1993

Augmented resting sympathetic activity in awake patients with obstructive sleep apnea.

Muscle nerve sympathetic activity (MSA) was recorded during wakefulness in 11 patients with obstructive sleep apnea (OSA) and in 9 sex- and age-matched healthy control subjects. Plasma levels of norepinephrine (NE) and neuropeptide Y were analyzed. Five patients had established hypertension (resting supine systolic BP/diastolic BP > or = 160/95 mm Hg). The investigation was performed after a minimum of 3 weeks' washout period of antihypertensive medication. Muscle sympathetic activity during supine rest was higher in patients compared with controls (p < 0.01) with no difference between normotensive and hypertensive patients. However, systolic, but not diastolic, BP was positively related to resting MSA (n = 20, p < 0.01). There was no significant correlation between body mass index and MSA. Resting MSA was unrelated to disease severity expressed as apnea frequency or minimum SaO2 during the overnight recording. Both the arterial and venous plasma norepinephrine was higher in patients compared with controls (p < 0.05). Plasma levels of NE correlated to resting MSA (p < 0.01) in the whole study group (patients and controls) but not within the respective subgroups. No significant correlation, however, was found between plasma NE (arterial and venous) and BP. Plasma neuropeptide Y-like immunoreactivity was similar in patients and controls. However, one patient with hypertension had approximately twice this level in repeated samples. It is concluded that neurogenic sympathetic activity as well as circulating plasma NE is increased in patients with OSA. This increased sympathetic activity during awake supine rest may reflect a pathophysiologic adaptation to hypoxia and hemodynamic changes occurring at repetitive apneas during sleep. The correlation between MSA and systolic BP implies that this mechanism may be directly or indirectly involved in the development of cardiovascular complications in OSA.

Adult↗