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Biomedical subjects

J Hedner

Publications and source records attributed to J Hedner.

At least 91 records · Page 5Linked to original sources

Left ventricular hypertrophy independent of hypertension in patients with obstructive sleep apnoea.

To evaluate cardiac structure and function as well as blood pressure in the obstructive sleep apnoea syndrome (OSAS), we investigated 61 male patients and 61 male controls with M-mode and two-dimensional echocardiography. All patients had a history of habitual snoring and a diagnosed light to severe OSAS by previous investigations of nocturnal oxygen saturation status. No subject in the control group had a history of OSAS or hypertension. Body weight was higher in the OSAS patients than in the controls (P less than 0.001). Fifty per cent (31 out of 61) of the OSAS patients had systemic hypertension; 17 of these 31 were on pharmacological antihypertensive treatment. Neither the systolic nor the diastolic blood pressures were found to correlate to the severity of the OSAS (desaturation index). The heart rate was higher at rest in the OSAS patients with or without systemic hypertension compared to the controls with or without a blood pressure level above 165/95 mmHg (P less than 0.05 and P less than 0.01, respectively). Left ventricular (LV) internal dimensions as assessed by echocardiography did not differ between the two groups, while the interventricular septum and the LV posterior wall were thicker in the OSAS group. Thus, the LV mass and the LV mass index were significantly higher among the OSAS patients (P less than 0.001 and P less than 0.001). The LV mass index was approximately 15% higher among the 30 normotensive OSAS patients with no history of cardiac disease compared with the normotensive controls (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Blunted renal response to atrial natriuretic peptide in congestive heart failure rats is reversed by the alpha 2-adrenergic agonist clonidine.

We wished to determine whether pharmacologic inhibition of the exaggerated sympathetic nerve activity in congestive heart failure (CHF) could restore the renal response to exogenous atrial natriuretic peptide (ANP) administration. Left ventricular (LV) myocardial infarction was induced in Sprague-Dawley rats (n = 16) by coronary artery ligature. Four to 6 weeks postoperatively, an isotonic saline (controls) or clonidine 5 micrograms/h infusion was given. Four hours later, all animals received incremental doses of rat ANP (99-126) (0.25, 0.5 and 1.0 microgram/kg/min). The continuous clonidine infusion transiently increased urinary volume (UV) as compared with the saline controls. Mean arterial pressure (MAP), heart rate (HR), and plasma norepinephrine (NE) were significantly decreased by clonidine. The graded ANP infusions significantly increased UV (saline 39.13 +/- 12.45 and clonidine 90.25 +/- 13.69 microliters/min, p less than 0.05) and UNaV (saline 4.26 +/- 1.10 and clonidine 8.81 +/- 1.59 mumol/min, p less than 0.05) in clonidine-pretreated rats as compared with saline-pretreated rats. We conclude that the diuretic and natriuretic responses to ANP are significantly increased in CHF after presynaptic inhibition of NE release by low-dose clonidine.

Animals↗

Local effects of substance P on respiratory regulation in the rat medulla oblongata.

The effect of substance P (SP) and the SP antagonist [D-Pro2,D-Trp7,9]-SP on basal ventilation was investigated in halothane-anesthetized rats. Microinjections of SP (0.4-1.5 nmol) into the ventrolateral medulla oblongata (VLM), (nuclei gigantocellularis, facialis, ambiguus, and reticularis lateralis) or into the dorsomedial medulla oblongata (DM, nucleus tractus solitarius) and its ventral surroundings dose dependently increased tidal volume (VT) and/or minute ventilation. In sensitive areas, the ventilatory stimulation was initiated within minutes, peaked around 8-10 min, and slowly returned to normal over 30-45 min after the injection. In the VLM sites, the increase in VT was generally accompanied by a decrease in respiratory frequency (f), whereas in the DM, f increased in parallel with VT. Furthermore, within the VLM, the respiratory response patterns differed with the definite location of the SP injection. A shortening of inspiratory time was observed in the ventromedial part, the ventrolateral portion of the nucleus paragigantocellularis and ventral to the nucleus facialis. In contrast, a lengthening of expiratory time was seen when SP was injected or applied more laterally along the ventral portion of nucleus facialis and near or directly on the ventral medullary surface. Application of [D-Pro2, D-Trp7,9]SP before or after SP completely antagonized the excitatory effects of SP on ventilation. The SP antagonist administered into the VLM decreased the ventilatory response to hypoxic breathing but caused no change during hyperoxic conditions.

Animals↗

Substance P in the ventrolateral medulla oblongata regulates ventilatory responses.

Local injection of substance P (SP) into the ventral portion of the nucleus gigantocellularis, nucleus reticularis lateralis, and nucleus retrofacialis of the ventrolateral medulla oblongata (VLM) or direct application on the ventral surface of the medulla oblongata caused marked stimulation of tidal volume (VT) and/or minute ventilation (VE). The ventilatory response to hypoxia was significantly blunted after SP in the VLM but not in the dorsal medulla oblongata (DM) (nucleus tractus solitarius). The SP antagonist [D-Pro2,D-Trp7,9]SP almost completely inhibited this response when applied locally to a wide area of the superficial layer of the VLM but not of the DM. Unilateral or bilateral application of 0.3-1.5 nmol of the SP antagonist in the VLM (corpus trapezoideum and the caudal region extending from the rootlets of the nucleus hypoglossus to the first cervical segment) markedly attenuated the response to a 5% CO2 inhalation. The inhibition of the CO2 response was seen after [D-Pro2,D-Trp7,9]SP in the rostral areas of the medulla oblongata corresponding to the corpus trapezoideum and the caudal region extending from the rootlets of the nucleus hypoglossus to the first cervical segment of the cervical cord. Electric somatosensory-induced ventilatory stimulation could be depressed by approximately 70% by [D-Pro2,D-Trp7,9]SP locally applied on the surface of the VLM. We conclude that SP is involved in the hypoxic, hypercapnic, and somatosensory ventilatory responses in the rat. However, these respiratory reflexes are mediated via different neuronal pools in the medulla oblongata, mainly the VLM.

Animals↗

Local application of somatostatin in the rat ventrolateral brain medulla induces apnea.

Local injections of the tetradecapeptide somatostatin (SOM) into the brain stem region were performed in anesthetized and decerebrate rats. SOM administration (0.6-1.8 nmol) into the nucleus paragigantocellularis and the nucleus reticularis lateralis of the ventrolateral medulla oblongata induced ventilatory depression and apnea. The occurrence of apnea was dose dependent and attributed to the anesthetic depth, and it was seen within 60-240 s after injection. In anesthetized rats the apnea was seen as a termination or a continuous decrease in tidal volume while respiratory frequency remained unaltered. SOM-induced apnea was caused by depression of central inspiratory drive. SOM injections into the dorsal medulla were ineffective in eliciting apnea, although a ventilatory depression but no apnea was induced in the awake unanesthetized state. In addition to its effect on basal ventilation, SOM administration in the ventrolateral medulla resulted in a blunted ventilatory response to hypoxic and hypercapnic stimuli in anesthetized rats. We conclude that SOM has potent inhibitory effects on respiration that are specifically located in the nucleus paragigantocellularis and the nucleus reticularis lateralis.

Animals↗

Inhaled salmeterol and salbutamol in asthmatic patients. An evaluation of asthma symptoms and the possible development of tachyphylaxis.

Salmeterol (SM) is a new beta 2-adrenoceptor agonist for inhaled use that has been shown to produce long-lasting bronchodilation in asthmatic patients. In the present study, evaluating efficacy and possible development of tachyphylaxis after SM, 12 patients with stable asthma were included after the demonstration of reversibility in FEV1 of at least 15% to 200 micrograms salbutamol (SB) or 20% to 500 micrograms SB. At inclusion all patients were receiving treatment with inhaled beta 2-agonists, and 11 of the 12 patients were also receiving inhaled corticosteroids. The patients were treated for two 2-wk periods with either inhaled SM 50 micrograms twice a day or SB 200 micrograms four times a day, following a double-blind, double-dummy, randomized design. The treatment periods were separated by a washout period of 1 wk. Dose-response curves to inhaled SB were obtained the day before and the day after each treatment period. On each of these days, basal FEV1, tremor, heart rate, and blood pressure were recorded and were then followed after the inhalation of 100 + 300 + 900 micrograms SB to obtain a cumulative dose-response curve. During the treatment periods, as well as during the washout week after each treatment, the patients recorded their morning and evening peak expiratory flow (PEF) each day before the inhalation of the study drug. Subjective asthma symptoms were monitored by a visual analog scale after each treatment period. The dose-response curves to SB revealed no signs of a reduced response to SB after any of the treatments, but significant increases in basal FEV1 and FVC were seen after the SM period (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗

Effects of dilevalol, a beta-adrenoceptor antagonist with intrinsic sympathetic activity in asthmatic patients.

The effects on baseline ventilation as well as beta 2-receptor stimulant-induced bronchodilation and tremor of atenolol and dilevalol, a beta-blocking agent with non-selective beta-antagonistic properties and intrinsic activity on the beta 2-receptor were evaluated in 8 patients with stable asthma. Both atenolol and dilevalol were found to significantly decrease both forced expiratory volume during 1 s (FEV1) and forced vital capacity (FVC). This decrease was significantly more pronounced after atenolol. Both agents decreased systolic and diastolic blood pressure as well as heart rate to a similar degree. Increased activation of beta 2-adrenoceptors by terbutaline infusion resulted in increased FEV1 and FVC as well as beta 2-adrenoceptor mediated reflex tachycardia and skeletal muscle tremor. The dose response curves for all these parameters were significantly shifted to the right and a decrease of the maximum relative response was seen after atenolol pretreatment. This effect was more pronounced after treatment with dilevalol with a further shift to the right of the response curve and a decrease of the maximum relative response. The haemodynamic and ventilatory effects of dilevalol are consistent with a non-selective beta-adrenoceptor blockade combined with intrinsic activity on the beta 2-receptors.

Adrenergic beta-Antagonists↗

Atrial natriuretic peptide (ANP) in relation to blood pressure: a study in middle-aged men with normal and elevated blood pressure.

In order to investigate the potential role of atrial natriuretic peptide (ANP) in mild to moderate essential hypertension, a study was conducted in groups of normotensive and hypertensive middle-aged men born in 1926 and 1927. Venous plasma concentrations of immunoreactive ANP (irANP) were studied in relation to measurements of cardiac structure and function, urinary electrolytes as well as some cardiovascular hormones. Plasma irANP did not differ between normotensive controls (31 +/- 14 pmol l-1) and borderline or untreated hypertensive patients. However, irANP concentrations were slightly but significantly (P less than 0.05) lower in the borderline (26 +/- 8 pmol l-1) compared to the untreated established hypertensives (35 +/- 14 pmol l-1). No relationships were found between irANP and blood pressure, indices of left ventricular structure and function or hormone parameters in subgroups or the whole study group. Our data do not support the view that plasma irANP is increased in uncomplicated essential hypertension, since our groups of borderline or established hypertensive middle-aged men without major cardiac involvement did not differ in irANP concentrations compared to normotensive controls. Thus, during the development or in the early stages of essential hypertension, ANP secretion does not seem to be abnormal.

Antihypertensive Agents↗

Relationship between renal sympathetic activity and diuretic effects of atrial natriuretic peptide (ANP) in the rat.

The effects of various adrenergic agonists and antagonists on the diuretic/natriuretic effects of rANP (103-125) were investigated in conscious and anaesthetized normotensive rats. Pharmacological sympathetic inhibition by reserpine completely inhibited the diuretic/natriuretic effects of ANP. However, surgical renal nerve denervation did not influence the renal response to ANP. Further studies using various pharmacological agents which interfere with adrenergic activity revealed that the diuretic mechanism of action differed between conscious and anaesthetized animals. In the anaesthetized group only, dopamine (D1) blockade reduced ANP-induced diuresis. In the conscious as well as anaesthetized rats, however, pre-synaptic dopamine (D2) stimulation and alpha 2-adrenergic receptor blockade effectively inhibited the renal response to ANP. The results of this study are compatible with the notion that ANP acts indirectly within the kidney via interaction with dopamine-containing neuronal or non-neuronal structures in the kidney.

Adrenergic alpha-Agonists↗

Renal interaction between sympathetic activity and ANP in rats with chronic ischaemic heart failure.

The diuretic and natriuretic effects of r-alpha-ANP (99-126) were investigated in rats with chronic ischaemic heart failure (IHF) produced by left coronary artery ligation. The plasma concentration of immunoreactive ANP (IrANP) was significantly higher, 91.8 +/- 16.0 pm in the IHF rats compared to 31.0 +/- 4.9 pm in sham-operated controls. In the control rats, ANP infusion (0.25-1.0 micrograms kg 1 mm 1) increased urine flow rate (V) and urinary sodium (UNa V) excretion. At the highest dose level, both V and UNa V were increased approximately fivefold. The diuresis and natriuresis seen in the control group after the infusion of ANP were blunted in the IHF rats. A bilateral surgical renal denervation in the IHF rats did not alter the renal dopamine levels, but induced a significant decrease in renal noradrenaline content, and almost completely restored the renal responsiveness to the ANP infusions. We conclude that renal denervation reversed the blunted renal excretory response to ANP in IHF rats. Thus, in experimental IHF, there seems to be a functional antagonism between efferent renal sympathetic nerve activity and ANP.

Animals↗

Cerebrospinal fluid concentrations of neurotensin and corticotropin-releasing factor in pediatric patients.

Cerebrospinal fluid (CSF) concentrations of neurotensin (NT) and corticotropin-releasing hormone (CRF)-like immunoreactive materials (LIM) were measured in 22 infants and children 6 days to 15 years of age. For both neuropeptides there was a marked age-related exponential decline in CSF concentrations. The most prominent decrease in CSF neuropeptide concentrations was seen during the first 24 months of postnatal life. From 1 year and on there was no or only minimal age-associated alteration in CSF neuropeptide concentrations. In this group of children (1-15 years) mean CSF concentrations of NT-LIM and CRF-LIM were 36.8 +/- 4.32 and 65.9 +/- 4.63 pg/ml, respectively. As CSF neuropeptide concentrations are apparently independent of circulating serum concentrations, they may reflect functional activity of neuropeptide-containing neurons and therefore may be of value in the assessment of the role of peptides in the human central nervous system function and behavior.

Adolescent↗

Evaluation of a new 'anti-snoring device'.

A new 'antisnoring device' based on the principle to induce a conditioned response was evaluated in 8 patients with habitual snoring. When patients snore the device starts to vibrate, making the snorers turn to the side position. Out of the 8 patients, 4 definite responders were identified. In these individuals the cumulative overnight sound produced above 40 dBA was clearly reduced. Moreover, these patients reported decreased daytime hypersomnolence but no change in sleep quality after using the antisnoring device for 4 weeks. Sleep staging did not reveal any significant changes in sleep architecture. However, two patients in the responder group were found to have increased rapid eye movement sleep time and time spent in stage 3 and 4, respectively. No changes in oxygen saturation were found in the responder or the nonresponder groups. The results indicate that the anti-snoring device may be useful to decrease snoring and to improve sleep in a subgroup of habitual snorers. The data do, however, not provide further information on the characteristics of this subgroup.

Adult↗

Atrial natriuretic peptide and catecholamines in peripheral blood as indicators of cardiac dysfunction in the general population.

1. From a screened cohort of 644 67-year-old men, drawn from the population of Gothenburg, 42 men with presumed cardiac dyspnoea were selected and compared with 45 random controls. 2. Cardiac function was evaluated by echocardiography and other non-invasive methods, and the potential of peripheral venous concentrations of immunoreactive atrial natriuretic peptide (IrANP), noradrenaline and adrenaline in revealing cardiac dysfunction was investigated. 3. Concentrations of venous IrANP and noradrenaline were both significantly, but weakly, related to the degree of dyspnoea and to pulmonary congestion. 4. IrANP, but not catecholamines, was also related to other indices of heart failure. The correlations were, however, due solely to increased immunoreactivity in men with severe dyspnoea; in most subjects with mild to moderate dyspnoea the level of IrANP was similar to that of the controls. 5. It is concluded that, in a population sample, the peripheral venous level of IrANP is more closely related to cardiac function than are catecholamines. Yet, the level of IrANP is not a very sensitive marker of cardiac dysfunction, suggesting that stimulation of alpha-human atrial natriuretic peptide release is a late phenomenon in the development of cardiac failure.

Aged↗

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↗

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↗

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↗