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Biomedical subjects

A Edlund

Publications and source records attributed to A Edlund.

At least 55 records · Page 3Linked to original sources
PubMed1988

Excretion of thromboxane A2 and prostacyclin metabolites during treadmill exercise in patients with intermittent claudication.

Platelet activation, with subsequent formation of thromboxane A2 (TxA2), is thought to play a role in the development of arterial occlusion. In patients with severe atherosclerosis of the lower limbs, characterized by leg ulcers and rest pain, the basal formation of TxA2 and prostacyclin (PGI2) is increased. Corresponding data in patients with more moderate atherosclerosis of the lower limbs have not been reported. Since the capacity to physical exercise is not blunted in such patients proper evaluation of their TxA2-PGI2 synthesis should comprise not only assessment of the basal formation, but also TxA2/PGI2 biosynthesis during conditions of elevated cardiovascular activity. To address this, we analysed these eicosanoids in patients with a history of intermittent claudication. Urinary dinor-metabolites of TxB2 and PGI2 (Tx-M and PGI-M, respectively) were estimated by gas chromatography/negative ion-chemical ionization mass spectrometry in samples collected prior to, during and immediately after 20 min of severe treadmill exertion. The basal excretion of Tx-M was 105 +/- 26 pg/mg creatinine. It was not changed during exercise, but increased to 176 +/- 48 pg/mg creatinine (P less than 0.05) during the recovery. The basal excretion of PGI-M was 142 +/- 25 pg/mg creatinine. The PGI-M response to exercise varied from no change at all to a 30-fold increase, without any obvious correlation to experienced leg pain, walking distance or other recorded variables. During the recovery period the outflow of PGI-M was significantly higher than at rest (482 +/- 145 pg/mg creatinine; P less than 0.01). We conclude that in patients with intermittent claudication due to atherosclerosis (1) platelet activation does not occur during the course of the exercise, and (2) vascular prostacyclin formation can be dissociated from of TxA2 synthesis. The observed increase in PGI-M in some of the patients is suggested to reflect tissue ischaemia induced by the lack of adequate hyperaemia during exercise.

6-Ketoprostaglandin F1 alpha↗
PubMed1987

Evidence for an anti-aggregatory effect of adenosine at physiological concentrations and for its role in the action of dipyridamole.

The effects of physiological adenosine concentrations on platelet aggregation in vitro were studied. Furthermore, we evaluated the effect of elevated adenosine levels in vivo, produced by the administration of dipyridamole, on platelet aggregation in whole blood. Platelet aggregation in plasma was significantly inhibited in vitro by adenosine at all concentrations tested in the physiological range (0.1-1.0 microM, 14-63% inhibition). Dipyridamole by itself had no effect at a therapeutic plasma concentration in vitro. Ten patients with ischaemic cerebrovascular disease were given 100 mg dipyridamole orally, and the level of adenosine increased from 0.22 to 0.29 microM (p less than 0.05). This was accompanied by a decrease in ADP-induced platelet aggregation in whole blood (17 to 15 ohms, p less than 0.05). When dipyridamole was infused in 11 healthy subjects, the adenosine level was not significantly elevated but the platelet aggregation was inhibited (from 13 to 11 ohms, p less than 0.05). It is concluded that adenosine may be of importance in the physiological regulation of platelet aggregation. Furthermore, dipyridamole treatment is associated with an anti-aggregatory effect that is probably mediated by its effect on endogenous adenosine levels.

Adenosine↗
PubMed1987

NADH content and lactate production in the perfused rabbit heart.

The influence of oxygen availability and absence of contractile activity on the NADH content and lactate production were investigated in the rabbit heart. Isolated hearts were perfused according to Langendorff with a modified Tyrode solution, saturated with a gas mixture containing either 95% O2:5% CO2 (control), 50% O2:5% CO2 in N2 (hypoxia), or 5% CO2 in N2 (anoxia). In another series of hearts cardiac arrest was induced by perfusion with Tyrode solution (95% O2:5% CO2) where the KCl concentration was increased to 15 mmol l-1 (hyperkalemia). Oxygen uptake (VO2) was similar in hypoxic and control hearts (P greater than 0.05), whereas lactate production was four-fold higher during hypoxia vs. control (P less than 0.01). Hyperkalemia resulted in a 60% decrease in VO2 (P less than 0.05), and no significant change in lactate production vs. control (P greater than 0.05). Both PCr and ATP were substantially decreased only during anoxia. Muscle NADH, whose changes reflect those within the mitochondria, averaged (+/- SE) 0.074 +/- 0.010, 0.153 +/- 0.016, 0.486 +/- 0.162 and 1.771 +/- 0.091 mmol kg-1 dry wt during control, hyperkalemia, hypoxia and anoxia, respectively. It is concluded that: muscle contraction during conditions of adequate oxygen supply results in an oxidation of mitochondrial NADH (presumably due to ADP stimulation of respiration), and a decreased oxygen availability results in an increase in NADH and an accelerated lactate production, although the VO2 is not affected.

Animals↗
PubMed1987

Vascular effects of infused adenosine are not mediated by prostacyclin release in humans.

Adenosine may contribute to the regulation of tissue blood flow directly and via release of vasoactive substances. For example, in the isolated, perfused heart, the nucleoside has been reported to release prostacyclin, a potent vasodilator. In humans, minor variations in prostacyclin release into the circulation result in readily detectable changes in the urinary excretion of its metabolite, 2,3-dinor-6-ketoprostaglandin (PG) F1 alpha, as measured by negative ion-chemical ionization gas chromatography-mass spectrometry. To test the hypothesis that prostacyclin participates in or mediates the vascular effects of adenosine, we administered adenosine (5.1 mg/min) or vehicle to healthy volunteers in random order as a 2-h infusion into the femoral artery under double-blind conditions. The plasma levels of adenosine, inosine, and hypoxanthine increased significantly during infusion of active drug, but the urinary excretion of adenosine and uric acid were unchanged, implying efficient tissue uptake of the infused nucleoside. Adenosine, but not vehicle, significantly (P less than 0.01) increased leg blood flow (from 2.7 +/- 0.3 to 8.7 +/- 2.5 ml X 100 ml tissue-1 X min-1), heart rate (from 66 +/- 3 to 80 +/- 4 beats/min), and urinary epinephrine excretion (from 2.8 +/- 0.4 to 5.4 +/- 0.8 ng/mg creatinine). In contrast, the excretion of 2,3-dinor-6-keto-PGF1 alpha was unaltered by infusion of adenosine. We confirmed that biologically significant alterations in prostacyclin release in the lower limb vascular bed would be reflected by the urinary metabolite in experiments involving local infusion of prostacyclin at a rate below the threshold necessary to alter limb blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗
PubMed1986

Effect of prostacyclin on the severity of ischaemic injury in rabbit hearts subjected to coronary ligation.

The hypothesis that prostacyclin (PGI2) might have a direct cytoprotective action in ischaemic cardiac tissue was investigated. Myocardial ischaemia was induced in perfused rabbit hearts by ligating the left main coronary artery. Coronary flow, oxygen uptake, and turnover of lactate and purines were measured before and up to 120 min after coronary occlusion. After this, ischaemic tissue was separated from perfused myocardium, and levels of lactate, adenine nucleotides and creatine phosphate were determined in specimens from non ischaemic, ischaemic and border zones. PGI2 (final conc. 10(-7) M) was infused before or 30 min after ligation and the results were compared to those in control hearts. Coronary ligation reduced coronary flow and oxygen consumption by about 50%. The fractional extraction of lactate decreased from 20% to close to zero and purine release increased 5-fold. In the non-ischaemic area the tissue levels of ATP and creatine phosphate were high, with a low content of lactate, but in the ischaemic area the levels of ATP and creatine phosphate were considerably reduced and the content of lactate was high. Although coronary flow and oxygen uptake were elevated after treatment with PGI2, no change in lactate or purine turnover was observed. Neither the weight of the non-perfused myocardium nor the tissue levels of the adenine nucleotides, creatine phosphate and lactate were affected by PGI2 treatment. The data indicate that in this model, in which effects on cardiac work, collateral flow and platelets are eliminated, PGI2 does not limit ischaemic myocardial injury. Hence, the hypothesis of a direct cytoprotective action of PGI2 in ischaemic myocardial tissue was not supported.

Animals↗
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

Extractable and lipopolysaccharide fatty acid and hydroxy acid profiles from Desulfovibrio species.

An analysis of the phospholipid ester-linked and the lipopolysaccharide (LPS) fatty acids and hydroxy fatty acids of six lactate-utilizing Desulfovibrio-type sulfate-reducing bacteria (SRB) has been performed using capillary gas-liquid chromatography-mass spectrometry (GLC-MS). The concentrations of normal fatty acids were essentially similar, with the possible exception of a high content of normal fatty acids in the LPS of Desulfovibrio gigas. Determination of monounsaturated acid double bond configuration was performed by GLC-MS analysis of the derivatized fatty acids. A total of nine branched chain and eight straight chain monounsaturated fatty acids was detected in the Desulfovibrio species analyzed. The major component detected in five Desulfovibrio was the 17-carbon iso-branched monoenoic acid which showed cis unsaturation [i17:1(n-7)c] seven carbons from the terminal methyl group of the fatty acid chain. D. gigas, in contrast, contained almost no unsaturated fatty acids and was greatly enriched in iso-branched 15:0. Major differences between strains were found in the phospholipid and LPS hydroxy fatty acids. These components, in addition to the i17:1(n-7)c and other characteristic branched chain unsaturated acids, can possibly be utilized as signatures of the lactate-utilizing SRB.

Desulfovibrio↗
PubMed1984

Central and peripheral haemodynamic effects of non-steroidal anti-inflammatory drugs in man.

The haemodynamic effects of non-steroidal anti-inflammatory (NSAI) drugs can be attributed either to their common property of inhibiting the formation of prostaglandins (PG) in the cardiovascular system, or to direct actions on the tone and sensitivity of the resistance vessels in various regions. Indomethacin (IND) is the most frequently studied NSAI drug, in animals and in man. Its cardiovascular effects differ somewhat from those of other NSAI, due to the fact that, besides inhibiting PG formation, IND acts as a direct vasoconstrictor. The stimulatory effect of IND in vascular smooth muscle results in an increased systemic vascular resistance which, although partially compensated by a decreased cardiac output, gives rise to a moderate increase in systemic blood pressure. The vasoconstrictor effect of IND is of particular interest in patients with ischemic heart disease, since it lowers their already decreased coronary flow, and may thereby accentuate the risk of myocardial infarction. Administration of IND also leads to a decreased blood flow in the splanchnic region, the kidneys, and the brain. The cerebral blood flow is lowered by 25-35%; in addition, IND almost entirely erases the hyperemic flow response to hypercapnia. Of other NSAI drugs, at least aspirin and naproxen are completely devoid of such actions on the cerebral circulation. A common vascular effect of all NSAI drugs is a diminution of reactive hyperemia, the local hyperemia that develops in a tissue subjected to a short period of arterial occlusion. Part of this hyperemic response is dependent on an intact vascular PG formation and consequently it is inhibited when PG formation is blocked. In contrast, NSAI drugs do not affect the functional increase in the blood flow in working skeletal muscle.

Adult↗
PubMed1983

Hypoxia elicits liberation of anti-aggregatory substances from isolated rabbit hearts.

The hypothesis was investigated that myocardial hypoxia stimulates the production of platelet anti-aggregatory substances in the heart. Rabbit hearts were perfused under normoxic or hypoxic conditions and the coronary and interstitial effluents from the hearts were separated. The occurrence of anti-aggregatory activity (AAA) in the interstitial effluent was detected in vitro from its capacity to inhibit ADP-induced platelet aggregation. The AAA in the effluent was deemed to be prostacyclin (PGI2) if its release was abolished by administration of indomethacin (5 X 10(-5) M) to the heart, and to be adenosine if it was abolished by incubation of the effluent with adenosine deaminase. During normoxic perfusion, only a minor efflux of AAA appeared from the heart; neither was the efflux appreciable during mild hypoxia (30 or 60% O2). Severe hypoxia (venous pO2 below 5 kPa), on the other hand, was associated with a marked release of AAA. Incubation of hypoxic effluent with adenosine deaminase resulted in a small loss of activity, indicating that the major part of the AAA was not ascribable to adenosine. After indomethacin treatment, significant amounts of AAA still appeared in the effluent during hypoxia. However, unlike the case before indomethacin, this AAA was completely destroyed by adenosine deaminase. From these data, we conclude that myocardial hypoxia can mobilize either of two independent mechanisms for protection against platelet aggregation: an activation of the synthesis and release of prostacyclin, and a more complete breakdown of ATP, leading to an increased formation and efflux of adenosine.

Adenosine↗
PubMed1983

Release of two vasodilators, adenosine and prostacyclin, from isolated rabbit hearts during controlled hypoxia.

The release of two locally formed vasodilators, adenosine and prostacyclin (PGI2), from hearts subjected to different degrees of hypoxia was investigated. Isolated rabbit hearts were perfused according to Langendorff with Tyrode solution, saturated with gas mixtures containing 8-95% O2 and 5% CO2 in N2. Coronary flow rate, O2 extraction and uptake, and cardiac production of lactate, purines and 6-keto-PGF1 alpha (the stable metabolite of PGI2) were determined. During perfusion of the hearts with a solution saturated with 95% O2, release of lactate, 6-keto-PGF1 alpha and purines was very low: lactate was liberated at a rate of about 5 mumol/100 g . min, purine release corresponded to 2% of the total adenosine nucleotide content of the heart per hour and the release of 6-keto-PGF1 alpha was about 150 mumol/100 g . min. During hypoxia there was a graded release of lactate and purines from the heart, as well as a liberation of 6-keto-PGF1 alpha. Mild hypoxia (60% O2 in the gas mixture) elicited a 160% increase in the formation of lactate and a 40% increase in the release of purines. During severe hypoxia (8% O2 in the gas mixture) the release of lactate and purines increased by more than 2000%. In contrast, the release of 6-keto-PGF1 alpha never increased more than 80% at any degree of hypoxia, neither did it correlate to the severity of the hypoxia. From these data we conclude that of the two vasodilating agents formed in the heart, adenosine and prostacyclin, the former is probably more important in the regulation of coronary flow.

6-Ketoprostaglandin F1 alpha↗