| 1. |
- Hedner, Jan A, 1953, et al.
(författare)
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An analysis of the mechanism by which gamma-aminobutyric acid depresses ventilation in the rat.
- 1984
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Ingår i: Journal of applied physiology: respiratory, environmental and exercise physiology. - : American Physiological Society. - 0161-7567. ; 56:4, s. 849-56
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Tidskriftsartikel (refereegranskat)abstract
- Intracerebroventricular administration of gamma-aminobutyric acid (GABA) or intraperitoneal injection of the GABA transaminase A inhibitor aminooxyacetic acid (AOAA) depressed ventilation in halothane-anesthetized rats. The depression was due to changes in both respiratory frequency (f) and tidal volume (VT) after GABA, whereas AOAA decreased only f. Intracerebroventricular GABA decreased inspiratory drive (VT/TI; intrapulmonary pressure at 100 ms) but did not change the bulbopontine setting of inspiratory duration (TI). Moreover, respiratory duty cycle (TI/TT) was decreased, and the ventilatory response to CO2 exposure was blunted. The ventilatory depression induced by GABA was reversed by the GABA antagonist bicuculline. The GABA content measured 45 min after AOAA administration was significantly increased in the whole brain, the hemispheres, striatum, and lower spinal cord regions. Whole-brain GABA content was significantly correlated to the changes in f, minute ventilation, TI, expiratory duration (TE), and total cycle duration. Furthermore, there was a significant negative correlation between brain stem GABA content and TI/TT but not VT/TI. In summary, GABA seems to interact with the central regulation of respiration at different levels in the brain. The main effect of increased endogenous concentrations of GABA is, however, a decrease in respiratory frequency due to a prolongation in TE.
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| 2. |
- Hedner, Jan A, 1953, et al.
(författare)
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Effects of TRH and TRH analogues on the central regulation of breathing in the rat.
- 1983
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Ingår i: Acta physiologica Scandinavica. - : Wiley. - 0001-6772 .- 1365-201X. ; 117:3, s. 427-37
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Tidskriftsartikel (refereegranskat)abstract
- Respiratory activity was studied in rats during light halothane anesthesia. Thyrotropin releasing hormone (TRH) and two TRH analogues: the desamidated form (TRH-OH) and gamma-butyrolactone-gamma-carbonyl-L-histidyl-L-prolinamide citrate (DN 1417) were administered intracerebroventricularly. TRH 0.5-5 micrograms induced a marked tachypnoea with a rapid onset and a duration of at least 20 min. DN 1417, a potent analogue of TRH with a very low TSH (thyroid stimulating hormone) releasing activity was more effective in stimulating respiratory frequency, while TRH-OH, regarded to have neither TSH releasing nor extra hypothalamic effects, at equimolar doses was unable to induce any changes in the respiratory pattern. When TRH was given into the fourth ventricle the dose response curve was slightly shifted to the left. In experiments employing the occluded breath technique, P0.1 was increased in the same magnitude as the mean inspiratory flow (VT/T1). The results also indicated an increase in the gain of the inflation reflex loop whereas the central bulbopontine setting for T1 and TTOT were not significantly changed. Local injection of TRH into the nucleus tractus solitarii induced a stimulation of respiratory frequency which was slower in onset compared to the response seen after injection into the lateral or fourth ventricles. Concomitantly to the respiratory changes, i.c.v. TRH injection induced a hypocarbia and an alkalosis. No changes in blood pressure or heart rate were seen. The respiratory stimulant effect of TRH could be potentiated by pretreatment with naloxone, methylatropine or a low dose of GABA. Haloperidol or propranolol did not significantly change the respiratory effects of TRH, while reserpine pretreatment seemed to blunt some of the ventilatory effects of TRH. It seems likely that TRH has few direct effects on brain stem neurones involved in the central regulation of respiration, but the main effects seem to be elicited in areas rostral to the brain stem. The respiratory stimulating effect of TRH is unrelated to TSH. Furthermore, other neurotransmitter systems might also be involved in modulation of the respiratory stimulation evoked by TRH.
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| 3. |
- Hedner, Jan A, 1953, et al.
(författare)
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Interaction of substance P with the respiratory control system in the rat.
- 1984
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Ingår i: The Journal of pharmacology and experimental therapeutics. - 0022-3565. ; 228:1, s. 196-201
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Tidskriftsartikel (refereegranskat)abstract
- The effects of substance P (SP) on respiratory regulation were studied in halothane-anesthetized rats. Intracerebroventricular injections of SP in the dose range 3 to 30 micrograms (3 X 10(-9) to 3 X 10(-8) mol) induced a dose-dependent stimulation of minute ventilation due to an increase in tidal volume although respiratory frequency was slightly decreased. Inspiratory drive (tidal volume/inspiratory time; P0.1) increased whereas respiratory duty cycle (inspiratory time/total cycle duration) remained unchanged. Animals subjected to bilateral vagotomy showed a similar response to i.c.v. SP with the exception that the increase in tidal volume was less pronounced and inspiratory time/total cycle duration was decreased. When applying the occluded breath technique it was found that maximum pressure indicating inspiratory off-switch threshold mechanisms was increased in vagi-intact animals after SP. Furthermore, SP altered the vagally mediated control of the length of the inspiratory phase and induced a shortening of the bulbopontine setting for inspiratory time. A biphasic circulatory response with an initial depressor effect followed by a slight pressor effect was also seen after i.c.v. SP. It is concluded that SP interacts with the respiratory control system by at least two different mechanisms, bulbopontine time setting and inspiratory off-switch mechanisms. SP may also directly increase central inspiratory activity.
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| 4. |
- Hedner, Thomas, 1949, et al.
(författare)
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Effects of theophylline on adenosine-induced respiratory depression in the preterm rabbit.
- 1984
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Ingår i: European journal of respiratory diseases. - 0106-4339. ; 65:2, s. 153-6
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Tidskriftsartikel (refereegranskat)abstract
- The adenosine agonist N6-phenylisopropyladenosine (PIA) was given intraperitoneally to preterm rabbit neonates (29 days gestational age). 1 mg i.p. induced a marked respiratory depression and irregular breathing which could be prevented or antagonized by administration of theophylline. The results indicated a central nervous site of action and it is hypothesized that central adenosine overactivity may have a pathophysiological significance for the irregular breathing or apnea of prematurity sometimes seen in the human neonate.
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| 5. |
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| 6. |
- Wessberg, Per, 1954, et al.
(författare)
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Adenosine mechanisms in the regulation of breathing in the rat.
- 1984
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Ingår i: European journal of pharmacology. - 0014-2999. ; 106:1, s. 59-67
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 7. |
- Wessberg, Per, 1954, et al.
(författare)
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Central respiratory and cardiovascular effects in the rat of some putative neurotransmitter amino acids.
- 1983
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Ingår i: Naunyn-Schmiedeberg's archives of pharmacology. - 0028-1298. ; 323:1, s. 58-65
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Tidskriftsartikel (refereegranskat)abstract
- Respiratory performance was studied in halothane anesthetized rats after intracerebroventricular (i.c.v.) injection of beta-alanine, taurine or glycine (0.01--1 mg). The amino acids induced a marked decrease in both respiratory frequency (f) and tidal volume (VT), which was immediate and longlasting. The respiratory depressant action of glycine could readily be reversed by strychnine, a glycine antagonist. Measurement of respiratory time intervals, inspiratory time (TI), expiratory time (TE) and total cycle duration (TTOT), after administration of the putative neurotransmitter amino acids revealed that the effects on f were due to prolongation of the duration of expiration. The duration of inspiration was principally unaltered, but mean inspiratory flow (VT/TI) and respiratory timing (TI/TTOT) decreased. In experiments employing the occluded breath technique, P0.1 was reduced in the same magnitude as the mean inspiratory flow (VT/TI). The results also showed a change in central (bulbopontine) setting for TE, while the setting to TI was unaltered. An inert amino acid, valine, which was administered i.c.v. in the same doses, had no effects on respiratory parameters. Apart from the effects on basal ventilation of beta-alanine, taurine and glycine, the CO2 induced respiratory response was blunted. These three amino acids also depressed heart rate and mean arterial pressure. Although relatively high doses were used to induce the respiratory effects, it may be hypothetised that the putative neurotransmitters beta-alanine, taurine and glycine may have a physiological role in the central regulation of breathing.
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| 8. |
- Wessberg, Per, 1954, et al.
(författare)
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Effects of taurine and a taurine antagonist on some respiratory and cardiovascular parameters.
- 1983
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Ingår i: Life sciences. - 0024-3205. ; 33:17, s. 1649-55
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Tidskriftsartikel (refereegranskat)abstract
- Respiratory performance, heart rate and blood pressure were studied in halothane anesthetized rats after administration of taurine and the putative taurine antagonist 6-aminomethyl-3-methyl-4H-1,2,4-benzothiadiazine-1, 1-dioxide hydrochloride (TAG). Intracerebroventricular (i.c.v.) taurine depressed ventilation due to decreased inspiratory neural drive and depression of respiratory timing mechanisms. I.c.v. administration of 1-100 micrograms TAG caused no changes in the respiratory and circulatory parameters studied except at the highest dose interval where respiratory frequency and minute ventilation were depressed. The respiratory depression induced by taurine (0.2 mg) or beta-alanine (1 mg) was antagonized by administration of TAG (100 micrograms). However, TAG did not antagonize the respiratory effects induced by i.c.v. glycine or gamma-aminobutyric acid (GABA) in equipotent respiratory depressant doses. The decline in inspiratory neural drive as well as in "respiratory timing" after i.c.v. taurine was restituted toward control values by TAG. The hypotension and bradycardia induced by taurine were also antagonized by TAG. It is concluded that TAG seems to antagonize the depressant action of taurine and beta-alanine but not of GABA and glycine on respiratory performance. TAG might also possess some partial agonist activity in higher doses.
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| 9. |
- Celen, Yelda Turgut, et al.
(författare)
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Impact of Gender on Incident Diabetes Mellitus in Obstructive Sleep Apnea: A 16-Year Follow-Up
- 2010
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Ingår i: Journal of clinical sleep medicine. - 1550-9389. ; 6:3, s. 244-250
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Tidskriftsartikel (refereegranskat)abstract
- STUDY OBJECTIVE: To address the influence of gender and obstructive sleep apnea (OSA) on development of diabetes mellitus (DM) in a sleep clinic cohort. DESIGN: A longitudinal observational study. PARTICIPANTS: A consecutive middle-aged (30-69 years) sleep clinic cohort from 1991 (n=318; 254 men, 64 women) with eligible baseline characteristics, clinical charts, and information from the Swedish Hospital Discharge Registry were identified. Ten individuals with DM at baseline and 47 patients who died during the follow-up period were excluded. MEASUREMENTS: The remaining 261 subjects were asked to complete a postal questionnaire regarding concomitant diseases including DM, diagnosed by a physician. RESULTS: In total, 168 patients (64.4%) replied. The incidence of DM was 24.9% in patients with OSA (overnight oxygen desaturations > or =30 in 1991) compared with 10.8% in subjects without OSA (p = 0.020). New-onset DM in men was 19.1% in OSA vs. 11.1% in non-OSA (n.s.), while the corresponding values in women were 50.0% in OSA and 9.5% in non-OSA (p = 0.022). In a multivariate analysis, DM was predicted by OSA in women with an odds ratio (OR) of 11.8, but not by age, body mass index (BMI) at baseline, or weight change at followup. In men, only BMI (OR 1.16) predicted DM. CONCLUSION: The contribution of OSA to DM development seems to be gender-dependent and higher in women than in men.
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| 10. |
- Engström, Gunnar, et al.
(författare)
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Pulmonary function and atherosclerosis in the general population : causal associations and clinical implications
- 2024
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Ingår i: European Journal of Epidemiology. - : Springer Nature. - 0393-2990 .- 1573-7284. ; 39:1, s. 35-49
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Tidskriftsartikel (refereegranskat)abstract
- Reduced lung function is associated with cardiovascular mortality, but the relationships with atherosclerosis are unclear. The population-based Swedish CArdioPulmonary BioImage study measured lung function, emphysema, coronary CT angiography, coronary calcium, carotid plaques and ankle-brachial index in 29,593 men and women aged 50–64 years. The results were confirmed using 2-sample Mendelian randomization. Lower lung function and emphysema were associated with more atherosclerosis, but these relationships were attenuated after adjustment for cardiovascular risk factors. Lung function was not associated with coronary atherosclerosis in 14,524 never-smokers. No potentially causal effect of lung function on atherosclerosis, or vice versa, was found in the 2-sample Mendelian randomization analysis. Here we show that reduced lung function and atherosclerosis are correlated in the population, but probably not causally related. Assessing lung function in addition to conventional cardiovascular risk factors to gauge risk of subclinical atherosclerosis is probably not meaningful, but low lung function found by chance should alert for atherosclerosis.
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