PubMed Health⌕ Search

Biomedical subjects

A Sollevi

Publications and source records attributed to A Sollevi.

At least 145 records · Page 8Linked to original sources
PubMed1985

Renin release during controlled hypotension with sodium nitroprusside, nitroglycerin and adenosine: a comparative study in the dog.

The haemodynamic effects of i.v. infusions of sodium nitroprusside (SNP), nitroglycerin (TNG), and adenosine were studied in dogs in parallel with quantitative determinations of plasma renin activity (PRA) by radioimmunoassay. The drugs were given for controlled hypotension, and the mean arterial blood pressure (MABP) was decreased to approximately 50 mmHg (6.7 kPa). Arterial blood samples for PRA were collected at 10-min intervals. During the last interval the dogs were subjected to haemorrhagic shock. SNP-induced hypotension could be maintained only with a stepwise increase in infusion rate, from 11.8 to 16.0 micrograms X kg-1 X min-1 (P less than 0.05). TNG could not produce the desired blood pressure level, but gradually increasing doses induced a gradually decreasing MABP (80-60 mmHg) (10.7-8.0 kPa). During adenosine-induced hypotension, a perfectly stable blood pressure level was maintained without dose adjustments. Both SNP and TNG induced blood pressure-dependent increases in PRA, while no changes in PRA were seen during adenosine-induced hypotension. Nor could haemorrhagic shock, which induced further increases in PRA during SNP- and TNG-induced hypotension, alter PRA during adenosine infusions. We conclude that adenosine differs markedly from conventional hypotensive drugs such as SNP and TNG with respect to stability of action and dose requirements, and that this stability is related to an inhibited increase in renin release.

Adenosine↗
PubMed1985

Coronary flow regulation in patients with ischemic heart disease: release of purines and prostacyclin and the effect of inhibitors of prostaglandin formation.

The present investigation was undertaken to study cardiac release of adenosine and prostacyclin (prostaglandin [PG] I2) in patients with ischemic heart disease (IHD), and to assess coronary vascular resistance before and after inhibition of synthesis in such patients. In 48 patients with IHD, arterial and coronary sinus blood samples were taken at rest, during atrial pacing to angina, and after pacing. Levels of purines were determined by high-performance liquid chromatography and the PGI2 metabolite 6-keto-PGF1 alpha was measured with radioimmunoassay. Coronary sinus blood flow was determined with retrograde continuous thermodilution before and after oral administration of indomethacin, aspirin, naproxen, or ibuprofen. Atrial pacing induced myocardial ischemia, as evidenced by typical chest pain and arrested lactate extraction. Adenosine was extracted at rest, but during ischemia there was a significant release of its metabolite hypoxanthine, indicating increased myocardial breakdown of high-energy adenine nucleotides. Arterial and coronary sinus concentrations of 6-keto-PGF1 alpha were low and no significant differences between them were found. After administration of the PG-synthesis inhibitor indomethacin, coronary vascular resistance was elevated, as was the cardiac oxygen extraction. The three other PG-synthesis inhibitors (aspirin, naproxen, and ibuprofen) did not, however, induce any change in coronary vascular resistance or in the cardiac extraction of oxygen. On the basis of these data we suggest that in patients with IHD cardiac ischemia results in increased myocardial production and release of purines, cardiac ischemia does not elicit any detectable increase in coronary production of prostacyclin, and the increased coronary resistance induced by indomethacin does not reflect the involvement of locally formed PG in the maintenance of coronary flow, but is rather a direct effect of the drug.

Adenosine↗
PubMed1985

Adenosine spares platelets during cardiopulmonary bypass in man without causing systemic vasodilatation.

The effect of infusing adenosine during cardiopulmonary bypass (CPB) on platelet count and mean arterial blood pressure (MABP) was studied in 13 patients (age 42-74), with 12 patients (age 47-66) as controls. Adenosine infusion (0.1 mg/kg/min in a central vein) caused a ten- to twentyfold increase of the adenosine concentration in the venous blood to the oxygenator, while the arterial levels were close to basal values (0.3 +/- 0.1 microM). The platelet count was significantly higher in the treated than in the placebo group during and 30 min after CPB, but not on the postoperative day. The groups did not differ with regard to the postoperative blood loss from tube drainage. Adenosine did not cause major systemic vasodilation (MABP less than 30 mmHg) in any case, and the blood pressure levels showed no intergroup difference during CPB. However, seven control patients but none in the adenosine group required vasodilator treatment (sodium nitroprusside) during CPB to prevent MABP from exceeding 70 mmHg. We conclude that adenosine infusion during CPB in man spares platelets, with minor changes in blood pressure.

Adenosine↗
PubMed1984

Central and splanchnic hemodynamics in the dog during controlled hypotension with adenosine.

Central and splanchnic hemodynamic effects during controlled hypotension induced by the administration of the endogenous vasodilator adenosine were studied in ten artificially ventilated dogs under neurolept anesthesia. Adenosine was administered as a continuous infusion in the aorta (n = 3), in the inferior vena cava (n = 3), and after pretreatment with dipyridamole (which inhibits the cellular uptake of adenosine) (n = 4) in a dose sufficient to maintain a mean arterial blood pressure (MABP) level of approximately 50 mmHg. Observations were made before and after 20 min of controlled hypotension. Basal arterial plasma levels of adenosine were in the 10(-7) M range (means = 0.4 microM). The hemodynamic response was similar in all three settings. Adenosine caused a profound decrease in systemic vascular resistance (SVR) (52%, P less than 0.01) and preportal vascular resistance (PPR) (64%, P less than 0.01), while hepatic arterial vascular resistance ( HAR ) increased by 49% (P less than 0.05). Cardiac output increased (22%, P less than 0.05) through increase of stroke volume (77%, P less than 0.01), while heart rate decreased (28%, P less than 0.01). Whole-body oxygen uptake decreased (14%, P less than 0.01). Portal venous blood flow increased by 28% (P less than 0.05), whereas hepatic arterial blood flow decreased by 70% (P less than 0.01). In the preportal tissues, oxygen uptake decreased by 21% (P less than 0.01). In contrast, hepatic oxygen consumption increased (53%, P less than 0.05). Adenosine-induced hypotension was not associated with changes in plasma renin activity or the plasma concentration of norepinephrine. It is concluded that adenosine causes a rapidly induced and easily maintained hypotension and may be a potentially useful agent for controlled hypotension in patients.

Adenosine↗
PubMed1984

Controlled hypotension with adenosine in cerebral aneurysm surgery.

The cardiovascular effects of adenosine-induced controlled hypotension were studied in 10 patients undergoing cerebral aneurysm surgery. Adenosine and its metabolites were measured in arterial plasma using high-pressure liquid chromatography. Whole body and cerebral arteriovenous oxygen content differences (AVDO2), arterial lactate levels, and arteriojugular lactate differences were determined. In order to reduce the dose requirement of adenosine, the patients were pretreated with the adenosine uptake inhibitor, dipyridamole (0.3-0.4 mg . kg-1). During the infusion of adenosine (0.14 +/- 0.04 mg . kg-1 . min-1) the mean arterial blood pressure decreased by 43%, from 82 to 46 mmHg, during a mean hypotensive period of 32 min, without signs of tachyphylaxis. The arterial adenosine level increased from 0.15 +/- 0.02 to 2.45 +/- 0.65 microM (P less than 0.01). Hypotension was caused by a profound decrease in peripheral vascular resistance (61 +/- 3%, P less than 0.01), which was accompanied by an increase in cardiac output (44 +/- 9%, P less than 0.01). Heart rate increased moderately by 16 +/- 5% (P less than 0.01). Pulmonary vascular resistance and central venous pressures were unaffected. Arterial lactate and PaO2 were unchanged, while whole body oxygen consumption was decreased by 13 +/- 4% (P less than 0.05). The AVDO2 across the brain was decreased by 37 +/- 5% (P less than 0.05) without signs of lactate formation. The authors conclude that adenosine rapidly induces a stable and easily controlled hypotension in humans by dilation of arterial resistance vasculature.

Adenosine↗
PubMed1984

Relationship between arterial and venous adenosine levels and vasodilatation during ATP- and adenosine-infusion in dogs.

The hemodynamic effects of ATP and adenosine (i.v. infusions) were studied in dogs in parallel with quantitative determination of purines in plasma by HPLC. In two experiments, infusion were performed during treatment with dipyridamole, an uptake inhibitor of adenosine. A 50-60% reduction of mean arterial blood pressure (MABP) was induced by both ATP and adenosine at infusion rates ranging between 17-290 mumoles/min. Cardiac output was unaffected by the purine infusions, indicating that the reduction of MABP was caused by a reduction of the systemic vascular resistance. Elevated ATP and adenosine concentrations were seen in venous plasma (pulmonary artery) during infusion, while only approximately 10% recovered ATP had been degraded to adenosine. On the other hand, in arterial plasma, virtually all nucleotides had been eliminated whereas the adenosine concentrations in plasma ranged between 5 and 20 microM. The magnitude of the vasodilatation was strictly related to the arterial plasma adenosine level irrespective of whether ATP or adenosine was infused. Thus, adenosine probably mediates the vasodilatory effect of ATP.

Adenosine↗
PubMed1984

Theophylline antagonizes cardiovascular responses to dipyridamole in man without affecting increases in plasma adenosine.

Effects of the vasodilator dipyridamole (Dip) on plasma adenosine levels, heart rate, blood pressure and skin microcirculation were studied in 13 healthy male volunteers. Venous plasma concentrations of adenosine, catecholamines, dipyridamole and theophylline were determined by HPLC. Skin capillary blood cell velocity (CBV) was measured by videophotometric capillaroscopy in the finger nailfold. The adenosine uptake inhibitor Dip (approximately 1-3 microM in plasma) increased plasma adenosine from 0.15 +/- 0.03 to 0.29 +/- 0.03 microM (p less than 0.01) and heart rate (HR) by 13 +/- 2 beats/min (p less than 0.01) and reduced diastolic blood pressure by 6 +/- 2 mmHg (p less than 0.05). Dip did not significantly affect the skin circulation since basal CBV, digital pulse amplitude (DAPA), skin temperature and post-occlusive reactive hyperemia were unchanged. Plasma catecholamine levels were also unaffected. The adenosine receptor antagonist theophylline (45-55 microM in plasma) did not influence basal plasma catecholamine or adenosine levels, HR, blood pressure or skin microcirculation. Following theophylline Dip caused similar elevations of plasma adenosine but no changes in HR or blood pressures. Our results support the hypotheses that Dip dilates blood vessels in man by elevating endogenous adenosine and that theophylline acts as an adenosine antagonist. Under basal conditions, the skin microcirculation appears to be regulated mainly by factors other than adenosine.

Adenosine↗
PubMed1983

Influence of adenosine on the vascular responses to sympathetic nerve stimulation in the canine subcutaneous adipose tissue.

Adenosine appears to regulate resting blood flow in canine subcutaneous adipose tissue. Sympathetic nerve stimulation has been shown to enhance the adenosine production in this tissue. This study therefore tested the possibility that adenosine may influence the vascular responses to sympathetic nerve stimulation. Intraarterial infusion of adenosine (5-20 microM in arterial blood) increased the resting vascular conductance (from 0.048 +/- 0.007 to 0.095 +/- 0.013 ml . min-1 . 100 g-1. mmHg-1) and the percental reduction in vascular conductance due to sympathetic nerve stimulation (4 HZ) by 34 per cent (p less than 0.05) and to i.a. noradrenaline by 27 per cent (p less than 0.05). The vasodilator response due to nerve stimulation after alpha-blockade was reduced by adenosine. Dipyridamole (0.5-1.5 microM) + EHNA (3-10 microM), which increases plasma adenosine levels, had similar effects to adenosine, while theophylline (30-80 microM) decreased the vasoconstrictor response. The vasoconstrictor escape was enhanced by EHNA alone and in combination with dipyridamole, but was reduced by theophylline. On the other hand, the poststimulatory hyperemia was unaffected by adenosine, dipyridamole and EHNA, and theophylline. The results show that adenosine does not reduce the magnitude of the initial vasoconstrictor response in proportion to the increase in resting blood flow. The autoregulatory escape in adipose tissue during nerve stimulation appears to be mediated both by adenosine and by noradrenaline acting on beta-adrenoceptors. Poststimulatory hyperemia does not seem to be greatly influenced by exogenous or endogenous adenosine.

Adenine↗
PubMed1981

Role of adenosine in adipose tissue circulation.

The vasodilatory effect of adenosine and some related compounds were studied in subcutaneous adipose tissue in situ. The effects of three drugs that inhibit adenosine elimination; two adenosine uptake blockers, dipyridamole and dilazep, the adenosine deaminase inhibitor, EHNA, were also studied. Plasma levels of adenosine were simultaneously determined by HPLC. Adenosine was a potent vasodilator and 2- and 6-substituted analogues were even more potent. Tissue blood flow was linearly related to the venous plasma concentrations of adenosine. An elevation of adenosine in plasma from 0.25 to 0.5 Mu M enhanced blood flow by approximately 50%. A further increase to 1 mu M was associated with a doubling of adipose tissue blood flow. Adenosine also increased the vascular conductance and the capillary filtration coefficient, indicating that is is active on all sections of the vascular bed. Theophylline and caffeine (30- 100 mu M in arterial plasma) antagonized the vasodilatory effect of exogenous adenosine, abolished vasodilation due to EHNA+dipyridamole and reduced resting blood flow. The results suggest that adenosine plays a physiological role in regulating adipose tissue blood flow.

Adenine↗
PubMed1981

The antilipolytic effect of endogenous and exogenous adenosine in canine adipose tissue in situ.

The effects of adenosine, 2-Cl-adenosine, two adenosine uptake inhibitors (dipyridamole and dilazep) and the adenosine deaminase (ADA) inhibitor erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA) were studied on basal and stimulated lipolysis in subcutaneous adipose tissue. The basal lipolysis was unaffected by all agents. Lipolysis induced by nerve stimulation (4 Hz, 5 min) was dose-dependently antagonized (up to 100%) by close i.a. infusions of adenosine (1--40 microM in blood); if the nerve induced vasoconstriction was prevented by alpha-adrenoceptor-blockade. 2-Cl-adenosine was a more potent antilipolytic agent than adenosine. EHNA (3--10 microM in blood) did not inhibit stimulated lipolysis in vivo possibly because of the low ADA activity in fat cells. Dipyridamole (0.5--1.5 microM in blood) in combination with EHNA increased the venous plasma concentration of adenosine from 0.3 +/- 0.05 to 0.7 +/- 0.1 microM and enhanced the tissue concentration close to 3-fold. Lipolysis induced by nerve stimulation (4 Hz) was reduced by about 40% by dipyridamole + EHNA and that induced by close i.a. noradrenaline injection (20 nmol) by approximately 60%. It is concluded that adenosine is an antagonist of stimulated lipolysis in subcutaneous adipose tissue in situ in concentrations that are reached during prolonged sympathetic nerve stimulation.

2-Chloroadenosine↗
PubMed1981

The release of adenosine and inosine from canine subcutaneous adipose tissue by nerve stimulation and noradrenaline.

1. Plasma and adipose tissue purine nucleosides were assayed by reversed phase high-performance liquid chromatography after purification of the samples on phenylboronate affinity gel. 2. The adenosine content of unstimulated subcutaneous adipose tissue was close to 1 n-mole/g. The concentrations of adenosine and inosine in canine arterial plasma were 0.26 +/- 0.03 and 0.16 +/- 0.03 microM, respectively. In venous plasma from the canine subcutaneous adipose tissue the corresponding values were 0.32 +/- 0.04 and 0.28 +/- 0.06 microM under basal conditions. The arterio-venous concentration difference of adenosine was linearly dependent upon the arterial adenosine concentration. At arterial concentrations below 0.3 microM there was a net production of adenosine; above 0.3 microM there was a net extraction of approximately 77% of the adenosine. Adenosine was extensively eliminated in blood. The major part of this elimination could be accounted for by metabolism to inosine, hypoxanthine and uric acid. 3. Following sympathetic nerve stimulation (4 Hz for 20 min) the rate of adenosine outflow from adipose tissue increased from 0.33 +/- 0.22 to a peak value of 1.2 +/- 0.26 n-mole/min. This corresponds to a net release of 8.7 +/- 3.0 n-mole/100 g tissue. Inosine outflow rose from 0.64 +/- 0.37 to 5.3 +/- 1.4 n-mole/min, corresponding to a net release of 24.6 4/- 8.7 n-mole/100 g. Nerve stimulation also increased the release of [3H]purines from [3H]adenine pre-labelled adipose tissue. The fractional release increased 15-fold after stimulation. The radioactivity was mainly in the form of hypoxanthine, inosine and uric acid while adenosine was a minor component. When metabolism in blood was inhibited by dipyridamole and an adenosine deaminase inhibitor nerve-stimulation-induced release of [3H]purines was mainly in the form of adenosine. 4. Noradrenaline injection also induced a release of radioactive purines and of inosine. On the other hand, the outflow of endogenous adenosine was very small. 5. The present results demonstrate that under basal conditions adenosine is present in arterial and venous canine plasma. The free extracellular tissue level may be similar to the basal arterial adenosine concentration. Sympathetic nerve stimulation and noradrenaline induces a marked release of adenosine which is rapidly metabolized in the tissue and blood stream to inosine, hypoxanthine and uric acid. In adipose tissue the levels of adenosine reached after adrenergic stimulation appear high enough to be of physiological relevance.

Adenosine↗
PubMed1978

Antilipolytic effect of adenosine in isolated perifused fat cells.

Adenosine markedly inhibits cyclic AMP accumulation in isolated fat cells, whereas inhibitory effects of adenosine on lipopolysis have been difficult to demonstrate. The present study has been performed on isolated "perifused" fat cells where continuous monitoring of the lipolytic rate is possible and where modulating substances, such as adenosine, are not allowed to accumulate. Adenosine deaminase was ineffective as a lipolytic agent in perifused fat cells, suggesting no important background activity of adenosine in this system. Micromolar concentrations of adenosine inhibited lipolysis induced by noradrenaline (0.3--1 micrometer) and theophylline (1 mM). Theophylline was an effective lipolytic agent also in perifused fat cells suggesting that antagonism of adenosine is not the major mode of action of this drug on fat cells.

Adenosine↗
PubMed1978

Vascular and metabolic responses to adrenergic stimulation in isolated canine subcutaneous adipose tissue at normal and reduced temperature.

1. The circulatory and metabolic effects of temperature reduction were studied in autoperfused canine subcutaneous adipose tissue in situ. 2. Cooling the adipose tissue sufficiently to reduce venous effluent temperature by 5--6 degrees C decreased blood flow from an average of 6.4--4.1 ml. min-1 . 100g-1. 3. Vasoconstrictor responses to sympathetic nerve stimulation (4 HZ) and injected noradrenaline (5 n-mole) were potentiated by cooling while vasodilator components of the vascular responses, such as autoregulatory escape and post-stimulatory hyperaemia, were virtually abolished by this treatment. 4. Oxygen uptake was reduced by cooling without signs of tissue hypoxia. This reduced oxygen demand may partly cause the decrease in adipose tissue blood flow. 5. Cooling inhibited glycerol mobilization from the adipose tissue during sympathetic nerve stimulation. Post-stimulatory lipolysis was, however, not inhibited. In vitro studies with 'perifused' rat fat cells suggest that this may be due to impaired inactivation of the lipolytic process, rather than to changes in transmitter removal, following stimulation at low temperature. 6. Cooling inhibited the mobilization of fatty acids more than that of glycerol, suggesting increased re-esterification of fatty acids within the tissue at low temperature. 7. It is concluded that cooling increases the sensitivity to vasoconstrictor stimuli and that inhibition of metabolic vasodilator mechanisms play a role for this effect. The stimultaneous inhibition of activating and inactivating mechanisms could explain the unchanged vascular and lipolytic responses to brief stimuli. Some possible implications of the present findings for the physiology of adipose tissue during cooling are discussed.

Adipose Tissue↗