Biomedical subjects

A Sollevi

Publications and source records attributed to A Sollevi.

At least 127 records · Page 7Linked to original sources

PubMed1987

Additive renal effects of indomethacin and dipyridamole in man.

The effect of dipyridamole alone and in combination with indomethacin was studied in 11 water loaded rheumatic patients with normal kidney function. The adenosine uptake inhibitor dipyridamole and the prostaglandin synthesis inhibitor indomethacin decreased diuresis by 25-50% when given alone and by approximately 80% when combined. These effects were not associated with changes in renal PAH-clearance, but may be partially related to a fall in GFR. Sodium excretion was decreased in parallel with the fall in GFR. In addition, both indomethacin and dipyridamole reduced the free water clearance. Theophylline at therapeutic plasma levels reversed the reduction in GFR and transiently counteracted the inhibition of tubular water and sodium excretion induced by combined dipyridamole and indomethacin treatment. The results suggest that endogenous adenosine and prostaglandins are both involved in the control of renal function in man, and that drugs that affect these two autocoids may interact to cause adverse effects in man.

Adenosine↗

PubMed1987

Elevations of neuropeptide Y-like immunoreactivity and catecholamines in plasma on increased intracranial pressure in the pig.

Graded increases of intracranial pressure (ICP) in anaesthetized pigs induced elevations of plasma levels of neuropeptide Y (NPY)-like immunoreactivity (LI) and catecholamines, simultaneously with hypertension and tachycardia. Plasma adrenaline (ADR) increased at a lower ICP-level than did the plasma levels of noradrenaline (NA) and NPY-LI. At the maximal ICP elevation, 22.9 kPa (172 mmHg), plasma NPY-LI was increased about 10-fold, from 48 +/- 8 pmol/l in the basal state, while NA and ADR concentrations increased more than 100-fold. At this maximal ICP-level the plasma levels of NPY-LI were correlated to the concentrations of both NA (r = 0.87, P less than 0.01) and ADR (r = 0.92, P less than 0.001). Plasma NPY-LI continued to increase to about 1000 pmol/l, 10 min after the maximal elevation of ICP was discontinued, while the catecholamines then had declined considerably. A slight cardiac release of NPY-LI was observed at the maximal elevation of ICP. The half-life of NPY-LI in plasma was about 6 min upon systemic infusion. At plasma levels similar to those obtained upon maximal ICP elevation, exogenous NPY caused slight vasoconstriction in the spleen and skeletal muscle, but had no effects on coronary blood flow or systemic blood pressure. This suggests that NPY mainly exerts local actions after release from nerve endings, while levels of circulating NPY in plasma must be very high to influence blood flow in some organs. It is concluded that elevation of ICP results in hypertension and tachycardia related to elevated plasma levels of NPY-LI and catecholamines.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1987

Changes in cardiac metabolism, perfusion, ECG and plasma catecholamines during increased intracranial pressure in the pig.

The effects of graded elevations of intracranial pressure (ICP) on cardiac metabolism, blood flow and electrophysiology, and plasma catecholamines were studied in eight open-chest pigs. ICP was consecutively elevated from 15 +/- 3 mmHg in the control state to 40 +/- 4, 84 +/- 4 and 152 +/- 11 mmHg. Mean arterial blood pressure and heart rate were significantly increased at the two highest ICP levels. Cardiac oxygen uptake was also increased from 2.9 +/- 0.4 ml X min-1 to a maximum of 7.1 +/- 2.0 ml X min-1, and coronary sinus blood flow increased from 49 +/- 7 to 131 +/- 35 ml X min-1 at the highest ICP level. The transmyocardial blood flow distribution was unchanged, as determined by the microspheres technique. Arterial plasma catecholamine concentrations were significantly elevated at the two highest ICP levels, but noradrenaline overflow from the heart did not increase. The high arterial adrenaline concentrations (51 +/- 25 nmol X 1(-1) at the highest ICP level) may be responsible for the cardiac stimulation seen in these experiments. No signs of ischaemia, as judged by myocardial lactate production or the relative flow distribution to the endocardium were observed. Changes in the T-wave morphology appeared in the subendocardial ECG at all ICP levels, the changes being more prominent with increasing ICP levels. It is concluded that the increase in circulating catecholamine levels, adrenaline in particular, together with an elevation of afterload cause an increase of myocardial work, which may explain the T-wave changes in the ECG which are observed upon rapid elevation of intracranial pressure.

Action Potentials↗

PubMed1987

Effects of dipyridamole and theophylline on reactive hyperaemia in subcutaneous adipose tissue in humans.

The importance of adenosine for reactive hyperaemia in subcutaneous adipose tissue was studied in healthy volunteers, using the adenosine uptake inhibitor dipyridamole (bolus 0.1 mg/kg i.v. followed by infusion of 0.7 microgram/kg/min) and the adenosine receptor antagonist theophylline (4 or 6 mg/kg i.v.). Basal blood flow, total blood flow and hyperaemia (total minus basal flow) after a 20-min arterial occlusion were measured in the distal femoral region by the 133Xe washout technique with and without drug treatment. Basal blood flow (mean +/- SEM) was 2.4 +/- 0.3 ml/min/100 g, while total post-occlusive flow and total reactive hyperaemia were 97.3 +/- 8.4 and 61.8 +/- 6.5 ml/100 g, respectively, without drug treatment. Basal blood flow was unaffected by dipyridamole but the total flow and hyperaemia were enhanced by 49 +/- 24 and 60 +/- 31%, respectively (P less than 0.05 for both). This enhancement was due to increases in both amplitude and duration of the hyperaemia. Neither basal blood flow, total post-occlusive flow nor hyperaemia were significantly altered by theophylline. The amplitude of the enhanced hyperaemia during dipyridamole was not significantly counteracted by simultaneous theophylline treatment (6 mg/kg) but the duration of hyperaemia was reduced from 13 +/- 1 to 8 +/- 1 min (P less than 0.01). The results suggest that endogenous adenosine does not regulate basal blood flow or reactive hyperaemia of limited duration in human adipose tissue. However, reactive hyperaemia may be enhanced by pharmacological elevation of endogenous adenosine levels.

Adenosine↗

PubMed1987

ATP breakdown products in human skeletal muscle during prolonged exercise to exhaustion.

To study changes in muscle energy state during prolonged exercise, especially in relation to fatigue, muscle biopsies were obtained from seven healthy males working until exhaustion on a cycle ergometer at 68% (63-74%) of their maximal oxygen uptake. Biopsies were taken at rest, after 15 and 45 min of exercise and at exhaustion, and analysed for ATP, ADP, AMP, inosine monophosphate (IMP) and hypoxanthine content by high performance liquid chromatography (HPLC), and for creatine phosphate (CP), lactate and glycogen by enzymatic fluorometric techniques. Glycogen content at exhaustion was approximately 30% of the pre-exercise level. The CP content decreased steeply during the first 15 min of exercise (P less than 0.01) and continued to decrease during the rest of the exercise period (P less than 0.05). Pronounced increases in contents of IMP (64% P less than 0.001) and hypoxanthine (69%, P less than 0.05) were found when exhaustion was approaching. Furthermore, energy charge [EC; (ATP + 0.5 ADP)/(ATP + ADP + AMP)] was decreased at exhaustion (P less than 0.05). The increases in IMP and hypoxanthine which occurred when exhaustion was approaching during prolonged submaximal exercise together with the decrease in EC during this phase of exercise suggest a failure of the exercising skeletal muscle to regenerate ATP at exhaustion.

Adenosine Diphosphate↗

PubMed1987

The disappearance of adenosine from blood and platelet suspension in relation to the platelet cyclic AMP content.

Adenosine exerts anti-aggregatory effects on human platelets in vitro, probably by increasing intraplatelet levels of cyclic AMP. In addition, adenosine prevents platelet loss in vivo. We have studied the relationship between the concentration of adenosine in the platelet media and the level of cAMP. In PRP, exogenous adenosine (2-16 microM) was eliminated with a half-life close to 5 min. Approximately half of the added adenosine was deaminated (blocked by 1-2 microM EHNA), and half was eliminated by uptake into platelets (blocked by 2 microM dipyridamole). In whole blood the half-life for adenosine was much shorter, about 15 s. Addition of adenosine deaminase (0.3 microgram ml-1) to PRP resulted in a measured half-life for adenosine approximating that of whole blood. In PRP where adenosine was eliminated as quickly as in whole blood, the adenosine-mediated stimulation of cAMP was 35% lower than in PRP, and the cAMP response lasted 2 min versus 15 min in normal PRP. These results suggest that the magnitude and duration of adenosine's effect on platelets are markedly overestimated by studying platelet suspensions. In blood, the effect of adenosine is smaller in magnitude and very transient. The possibility is discussed that the action of adenosine in vivo on blood platelets can therefore be quite local.

Adenosine↗

PubMed1987

Release of neuropeptide Y upon haemorrhagic hypovolaemia in relation to vasoconstrictor effects in the pig.

Neuropeptide Y is co-stored with noradrenaline in peripheral sympathetic nerves, but is not present in the adrenal chromaffin cells in the pig. Plasma levels of neuropeptide Y-like immunoreactivity and catecholamines were studied upon haemorrhagic shock in the anaesthetized pig. The animals were bled in two successive steps (30 and 10 ml kg-1), resulting in a reduction of the mean arterial blood pressure by 44% and 53%, respectively. Plasma levels of noradrenaline increased abruptly after the first bleeding from 1.21 +/- 0.27 to 26.5 +/- 6.3 nmol l-1. Plasma neuropeptide Y showed a progressive increase from 62 +/- 8 pmol l-1 in the basal state to 365 +/- 98 pmol l-1 at 60 min after the first bleeding. After the second bleeding plasma neuropeptide Y and noradrenaline showed a largely parallel increase and finally reached levels of 2524 +/- 580 pmol l-1 and 316 +/- 117 nmol l-1, respectively. A veno-arterial gradient of neuropeptide Y and noradrenaline indicating local release was present over the spleen after both bleeding steps. The overflow of neuropeptide Y was delayed about 15 min compared to noradrenaline after the initial bleeding. Depletion of the neuropeptide Y content after shock in the heart and skeletal muscle supported local release also from these organs. Infusions of neuropeptide Y to obtain similar plasma concentrations as during shock (nM range) caused reduction in blood flow as determined by the radionuclide-labelled microsphere technique in several organs including spleen and skeletal muscle (threshold response at 319 +/- 22 pmol l-1) but not in heart and brain. In conclusion, both neuropeptide Y and noradrenaline were markedly elevated in plasma upon haemorrhagic shock, suggesting release from sympathetic nerve terminals. Neuropeptide Y could therefore have a role as a sympathetic neurotransmitter, and during severe stress, circulating plasma levels are in the range where vasoconstriction is evoked by exogenous NPY.

Animals↗

PubMed1987

The role of myogenic relaxation, adenosine and prostaglandins in human forearm reactive hyperaemia.

1. Forearm blood flow was measured bilaterally in healthy young male and female volunteers, in the basal state and after upper-arm occlusion of arterial or venous blood flow for 1-20 min. The investigations were repeated after pre-treatment with drugs affecting vascular prostaglandins and/or adenosine. 2. Simultaneous arterial occlusion in one arm and venous occlusion in the contralateral arm for up to 20 min elicited a considerable reactive hyperaemia in the arm subjected to arterial occlusion, but completely failed to elevate the post-occlusive flow in the arm subjected to venous occlusion above the pre-occlusive level. 3. When the arterial occlusion was increased from 1 to 20 min there was a progressive increase in the subsequent reactive hyperaemia, up to 30 ml 100 ml tissue-1. The time dependence following 1-3 min of arterial occlusion was based on a facilitation of the peak post-occlusive flow, while prolongation of the arterial occlusion from 3 to 20 min augmented the reactive hyperaemia mainly by increasing its duration. 4. Inhibition of prostaglandin synthesis with ibuprofen reduced the total reactive hyperaemia following 3-5 min of arterial occlusion by up to 70%. This attenuation was due both to a reduction of peak post-occlusive flow and to a shortening of the duration of the post-occlusive hyperaemia. 5. The adenosine receptor antagonist theophylline reduced the reactive hyperaemia following 5 min of arterial occlusion by about 35%. Combined treatment with ibuprofen and theophylline did not reduce the reactive hyperaemia more than either drug alone. 6. Infusion of dipyridamole, a drug which inhibits the elimination of adenosine, reinforced the reactive hyperaemia by about 45%. This effect of dipyridamole was completely inhibited by administration of theophylline, and also by ibuprofen. 7. Plasma levels of adenosine, hypoxanthine and uric acid were maintained during the reactive hyperaemia, indicating increased production of purines during or immediately after the ischaemia. 8. It is concluded that the adequate stimulus for vascular relaxation in response to interruption of blood flow is omission of vessel wall distension. Local metabolic factors like endogenously formed prostaglandins and adenosine may act synergistically to this myogenic response but seem to be inactive alone. The lack of additive effects of ibuprofen and theophylline suggests a link between vascular relaxation induced by prostaglandins and by adenosine.

Adenosine↗

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↗