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Biomedical subjects

A Sollevi

Publications and source records attributed to A Sollevi.

At least 127 records · Page 7Linked to original sources
PubMed1987

Preservation of myocardial high-energy phosphates in open-heart surgery with deep general hypothermia and multidose crystalloid cardioplegia.

Myocardial energy metabolism during deep general hypothermia (20 degrees C) and multidose crystalloid cardioplegia, and also during subsequent reperfusion, was studied in eight patients undergoing isolated aortic valve replacement. Six serial transmural biopsy samples from the left ventricular apex were analyzed for high-energy phosphates and their degradation products. Reductions in ATP, total adenine nucleotide content and energy charge were insignificant during cardioplegia, as were changes in adenosine and uric acid concentrations. During reperfusion, however, there was slight but significant reduction in total adenine nucleotide content, despite adequate oxygenation as indicated by reversal of lactate accumulation. These observations suggest that the reperfusion phase is accompanied by metabolic aberrations which are not overcome by good oxygenation in relation to the metabolic rate.

Adenine Nucleotides↗
PubMed1987

Clinical experience with adenosine for controlled hypotension during cerebral aneurysm surgery.

The cardiovascular effects of adenosine-induced hypotension were studied in 47 patients undergoing intracranial vascular surgery under neurolept anesthesia. Adenosine infusion (214 +/- 18 micrograms X kg-1 X min-1) decreased mean arterial pressure (MAP) by 42 +/- 1% from 80 +/- 1 to 46 +/- 1 mm Hg for an average of 29 +/- 5 min of hypotension. Hypotension was associated with a minor increase in heart rate (13 +/- 2%) and with prolongation of the PR interval (9 +/- 2%). ST-T depression did not occur except in one patient with a previous history of myocardial infarction. The adenosine-induced increase in cardiac index (42 +/- 9%, n = 7) was associated with a 63 +/- 10% decrease in systemic vascular resistance index (n = 7) while the pulmonary capillary wedge pressure remained unchanged. Adenosine metabolism was limited and there was no accumulation of the end metabolite, uric acid. Serum creatinine levels were normal in all patients postoperatively. We conclude that adenosine rapidly induces a stable and easily controlled hypotension in man without tachyphylaxis or rebound hypertension. There were no signs of renal or myocardial dysfunction except for dysrhythmias that occurred in two patients with a history of myocardial infarction.

Adenosine↗
PubMed1986

Frequency- and reserpine-dependent chemical coding of sympathetic transmission: differential release of noradrenaline and neuropeptide Y from pig spleen.

The importance of impulse pattern and stimulation frequency for the release of noradrenaline (NA) and the coexisting peptide neuropeptide Y (NPY) in relation to vasoconstriction (perfusion-pressure increase) was studied in the blood-perfused pig spleen in vivo. Splenic nerve stimulation with intermittent bursts at high frequency (20 Hz) caused a several-fold larger release of NPY-like immunoreactivity (-LI) in relation to NA than a continuous stimulation at a low frequency (2 Hz), giving the same total number of impulses. alpha-Adrenoceptor blockade by phentolamine enhanced markedly both NA and NPY release, especially at low stimulation frequency, suggesting prejunctional adrenergic inhibition of release. Addition of propranolol unmasked a large remaining perfusion-pressure response to nerve stimulation. Reserpine treatment reduced the NA content of the spleen as well as the stimulation-evoked NA release by greater than 90%. However, the perfusion-pressure increase in response to nerve stimulation was well maintained. A marked increase in the stimulation-evoked release of NPY-LI occurred after reserpine. Adrenoceptor blockade after reserpine treatment reduced only slightly the perfusion-pressure response in parallel with a decline in NPY output. NPY caused an adrenoceptor-resistant perfusion-pressure increase at plasma concentrations that were in the same range as the maximal increase during nerve stimulations. In conclusion, the present data suggest a frequency-dependent, chemical coding of sympathetic transmission with preferential release of the classical transmitter NA at low, continuous frequencies and release of NPY, mainly at high frequencies. Reserpine treatment enhances markedly NPY release, which may explain why the functional response is largely intact in spite of adrenoceptor blockade and marked NA depletion.

Adrenergic Fibers↗
PubMed1986

Cardiovascular effects of adenosine in man; possible clinical implications.

The results summarized above indicate that adenosine is a physiologically relevant modulator of the cardiovascular system in man. The levels of adenosine are low during resting conditions, but may increase during conditions of oxygen and/or substrate deficiency. Already the basal concentration seems to be sufficient to affect regional flow in vital organs such as the heart. Several drugs may act by increasing the levels of adenosine or by influencing its receptors. In addition, adenosine may be used in many clinical situations as a vasodilator, antiaggregatory compound as well as an antiarrythmic agent. Its effect is easy to control due to the extremely short plasma half-life. The dose range for the clinical effects are summarized in Table 6. Both the physiological and pharmacological aspect of adenosine are subject to intense study in several laboratories.

Adenosine↗
PubMed1986

Skeletal muscle oxygen pressure fields during controlled hypotension with adenosine and sodium nitroprusside. A comparative study in the rabbit.

The MDO (Mehrdraht Dortmund Oberfläche) multiwire oxygen electrode was used for studies of oxygen pressure fields in eight rabbit skeletal muscle preparations during controlled hypotension with adenosine and sodium nitroprusside (SNP). Tissue oxygen histograms were constructed from 120 simple tissue oxygen pressures (PtO2) samples that were collected during 5 min. Statistical analysis between histograms was performed with the two-sample Kolmogorov-Smirnov test. Mean arterial blood pressure was reduced to 60 mmHg with both drugs, corresponding to a 42-43% reduction during the 25-min hypotension period. SNP-induced hypotension caused significant reduction of muscle oxygenization (compared to normotensive controls) in six of the animals, while this occurred on three occasions during adenosine administration. When comparing the histograms during hypotension, the tissue oxygenation during adenosine infusion was higher than during SNP in five and equal to SNP in three animals. Low tissue oxygen pressure values (0-0.6 kPa) were four times more frequent during SNP than during adenosine hypotension, although systemic arterial oxygen pressures were unaffected. We conclude that controlled hypotension with adenosine preserves tissue oxygen pressures better than hypotension induced by SNP.

Adenosine↗
PubMed1986

Effect of adenosine-induced controlled hypotension on canine myocardial performance, blood flow and metabolism.

The effect of adenosine-induced controlled hypotension (CH) on myocardial performance, blood flow, and metabolism was studied in nine pentobarbital-anaesthetized, open-chest dogs. Adenosine was continuously infused i.v. (0.69 +/- 0.06 and 1.36 +/- 0.11 mg/kg/min) at two stepwise increased rates (12-14 min-periods) in order to induce approximately 20 and 40% reduction of the mean arterial pressure (MAP 62 +/- 4 and 43 +/- 1 mmHg, respectively). The reduction of MAP was associated with decreases in heart rate (6 +/- 2%, P less than 0.05 and 21 +/- 4%, P less than 0.01), left intraventricular systolic pressure (14 +/- 3%, P less than 0.01 and 32 +/- 3%, P less than 0.01), left ventricular end-diastolic pressure (23 +/- 9%, P less than 0.05 and 42 +/- 9%, P less than 0.01) and ventricular intramyocardial systolic pressure (15 +/- 6% n.s. and 27 +/- 6%, P less than 0.01). The rate pressure product was markedly reduced by 49 +/- 3% (P less than 0.01) at the highest infusion rate. The mean coronary vein pressure (20.3 +/- 2.8 mmHg) was unaffected by the adenosine infusion. The systolic pressure time index (SPTI) was decreased by 33 +/- 3% (P less than 0.01) during the highest infusion rate of adenosine, while the diastolic perfusion time index (DPTI) was 15.4 +/- 2.2 mmHg X s and remained unchanged. The DPTI:SPTI ratio increased by 40 +/- 13% (P less than 0.05), suggesting a sufficient endocardial oxygen supply.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗
PubMed1986

Cardiovascular effects of adenosine.

The results, briefly summarized above, indicate that adenosine could be a physiologically important modulator of several aspects of cardiovascular regulation. Most cells are equipped with adenosine receptors. These receptors are of at least two subtypes which can be defined by the relative agonist potency. At these adenosine receptors, methylxanthines, including caffeine and theophylline, act as competitive antagonists. The role of adenosine antagonism, as a mechanism behind the cardiovascular effects of these xanthines, was recently reviewed (Fredholm, 1984). The concentrations of adenosine are low during resting conditions, but may be raised substantially by, for example, hypoxia, ischaemia and increased mechanical or biochemical work. The adenosine levels can also be raised by drugs, including uptake inhibitors such as dipyridamole. Already the concentrations of adenosine that occur during basal conditions are sufficient to produce significant effects, for example, on blood-flow. When the concentrations are raised the importance of endogenous adenosine becomes even greater. Adenosine may not only be of physiological significance but may also be pharmacologically important. First, there are several drugs that may act by affecting the levels of adenosine or by influencing its receptors. Second, the possibility exists that adenosine itself could be used clinically. For example, adenosine may be an attractive alternative to sodium nitroprusside or nitroglycerin when controlled hypotension is to be achieved. Adenosine may also be used to preserve blood platelets during extracorporal circulation or to produce selective regional vasodilatation. Both the physiological and pharmacological aspects are subject to intense study in several laboratories.

Adenosine↗
PubMed1986

Effect of hypotension induced by sodium nitroprusside on catecholamine overflow in the canine kidney.

The overflow of noradrenaline (NA) and dopamine (DA) to plasma in the kidney in response to hypotension induced by sodium nitroprusside were studied in barbiturate-anaesthetized dogs in order to evaluate the possible existence of separately regulated renal noradrenergic and dopaminergic nerve fibres. When mean arterial blood pressure was lowered to 55 +/- 5 mmHg, arterial plasma NA, DA and adrenaline concentrations were increased and renal blood flow decreased. Renal sympathetic nerve activity was assessed by measuring the renal overflow of catecholamines to plasma. To obtain more accurate estimates of the renal contribution to catecholamines in renal venous plasma we corrected for the renal extraction of arterial catecholamines, assessed by the extraction of endogenous adrenaline. The corrected renal NA overflow to plasma increased from 164 +/- 52 to 419 +/- 137 pmol min-1 (P less than 0.05) during sodium nitroprusside induced hypotension. The renal overflow of DA to plasma was, however, not influenced significantly. The DA/NA ratio for renal venous plasma concentration as well as for renal overflow to plasma was decreased (P less than 0.05) by sodium nitroprusside induced renal nerve activation. In contrast, electrical renal nerve stimulation has previously been shown to enhance the overflows of DA and NA in parallel. One possible interpretation of these findings is that sodium nitroprusside selectively activated renal noradrenergic but not the putative dopaminergic nerve fibres while electrical stimulation activated both types of fibres.

Animals↗
PubMed1985

Increased concentration of hypoxanthine in human central cerebrospinal fluid after subarachnoid haemorrhage.

The adenine nucleotide metabolites hypoxanthine, xanthine and uric acid were determined by high performance liquid chromatography in cerebrospinal fluid (CSF) from 25 patients with subarachnoid haemorrhage (SAH) and from 26 control subjects. In addition, the haemoglobin and protein levels in the CSF of the patients were determined. In 13 subjects, from which lumbar CSF was collected three, six and nine days after SAH, there was a gradual increase in 8 patients for hypoxanthine and in 3 of the 13 patients for xanthine and uric acid. The mean concentrations were not significantly higher than the controls. In 12 SAH patients, consecutive CSF fractions of 10 ml were collected peroperatively during surgical clipping of aneurysms. The hypoxanthine concentrations increased continuously from lumbar to central CSF samples. Hypoxanthine levels were 6.5 +/- 1.0 microM in lumbar CSF compared to 11.8 +/- 2.3 microM in central CSF (p less than 0.001), while xanthine, uric acid, haemoglobin and protein levels were equally distributed. Furthermore, the SAH patients showed about 3 times higher concentrations of central CSF hypoxanthine (p less than 0.01) and xanthine (p less than 0.05) while that for uric acid was similar compared to all control subjects. Also, as in vitro study showed that the increased concentrations of the adenine nucleotide metabolites could not be caused by degradation of blood components in the subarachnoid space. It is presumed that the increased central CSF concentrations of hypoxanthine that were demonstrated in patients after SAH could be a sensitive marker for brain tissue ischaemia. However, since there was no correlation between the hypoxanthine levels, clinical condition or cerebral vascular diameter, other factors have to be excluded before ischaemia alone could explain the elevated central hypoxanthine levels in patients without major clinical dysfunction after SAH.

Adult↗
PubMed1985

Neuropeptide Y and sympathetic vascular control in man.

A parallel increase in systemic plasma levels of neuropeptide Y (NPY)-like immunoreactivity (LI) and noradrenaline (NA) was found during thoracotomy and surgery involving cardiopulmonary bypass in man. Thus, plasma levels of NPY-LI increased from 29 +/- 4 pmol/l before anaesthesia to 59 +/- 10 after thoracotomy and to 87 +/- 8 pmol/l upon cardiopulmonary bypass. The corresponding NA levels increased from 1.3 +/- 0.1 nmol/l before anaesthesia to 3.0 +/- 0.6 and 4.2 +/- 5 nmol/l after thoracotomy and cardiopulmonary bypass, respectively. A significant correlation was found between plasma levels of NPY-LI and NA during the operation but not between NPY-LI and adrenaline. The NPY-LI in human plasma was found to be similar to synthetic porcine NPY on reversed phase high performance liquid chromatography. Human submandibular arteries contained high levels of NPY-LI (24 +/- 3 pmol/g). In in vitro experiments on isolated human submandibular arteries, NPY in low concentrations (1000 pmol/l) was found to potentiate the contractile effects of NA or transmural nerve stimulation and to exert vasoconstrictor activity per se in higher concentrations. The calcium-entry antagonist nifedipine abolished both the NPY-induced contractions and the enhancement of NA-evoked contractions. NPY depressed the nerve stimulation-evoked 3H-NA release from human submandibular arteries via a prejunctional mechanism which was resistant to nifedipine. NPY contracted human mesenteric veins and renal arteries, but not mesenteric arteries. In conclusion, NPY seems to be co-released with NA upon sympathetic activation in man. Furthermore, NPY exerts both pre- and postjunctional effects on sympathetic control of human blood vessels.

Adult↗
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↗