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K Gréen

Publications and source records attributed to K Gréen.

At least 19 recordsLinked to original sources
PubMed1996

Profound decrease of in vivo formation of thromboxane during oestrogen therapy.

Oestrogen has been proposed to influence platelet activity and formation of the vasoactive eicosanoids thromboxane and prostacyclin. Previous studies have been based on ex vivo techniques with well-known artifacts during blood sampling and ex vivo conditions. The present study is the first to assess in vivo formation through gas chromatographic/mass spectrometric analysis of the major urinary metabolites 2,3-dinor-thromboxane B2 and 2,3-dinor-6-keto-PGF1 alpha. Ten consecutive male patients with prostatic carcinoma participating in a randomized study comparing the effects of parenteral oestrogen therapy (n = 5) with orchidectomy (n = 5) were included. Oestrogen was given as polyestradiol phosphate 240 mg i.m. every month, 2,3-dinor thromboxane B2 and 2,3-dinor-6-keto-PGF1 alpha were analysed with the help of tetradeuterated internal carriers/standards. We found a consistent decrease of in vivo formation of thromboxane by approximately 40% during parenteral oestrogen therapy (P = 0.008) and a doubling after surgical castration. The ratio of prostacyclin to thromboxane increased by approximately 50% (P = 0.023) during oestrogen therapy. In conclusion, oestrogen induced a marked decrease of in vivo formation of thromboxane and a marked increase in the ratio of prostacyclin to thromboxane formation in all patients. According to current knowledge this should be beneficial for the cardiovascular system. Furthermore, thromboxane formation increased after surgical castration. The latter fact should direct attention to the influence of androgens on thromboxane synthesis. Our findings discloses a marked sex-hormone sensitivity of the thromboxane-forming system.

Aged↗
PubMed1996

Prostanoid release after lung transplantation.

BACKGROUND: Increased pulmonary vascular resistance is frequently seen after lung transplantation. Thromboxane A2 is a potent vasoconstrictor of pulmonary arteries. Thromboxane-elicited vasoconstriction can ben counteracted by prostacyclin. The effects of lung transplantation on the biosynthesis of these substances were investigated. METHODS: Pulmonary artery flush perfusion with a low-potassium dextran glucose solution was performed in six donor pigs. After a 24-hour storage period, the left lung was transplanted into a recipient, followed by right pneumonectomy, making the recipient's survival entirely dependent on the transplanted lung. A sham operation (bilateral thoracotomy, right pneumonectomy) ws done in six pigs. the urine contents of the stable thromboxane A2 metabolite 2,3-dinor-thromboxane B2 and the stable prostacyclin metabolite 2,3-dinor-6-keto-protaglandin F1 alpha were measured with a gas chromatography-mass spectrometry method. RESULTS: One to four hours after reperfusion, thromboxane A2 production reached its maximum in both groups: it ws fivefold the basal value in the transplanted group, but only twofold in the sham-operated group, the difference being significant (p < 0.005). Twenty to twenty-four hours after reperfusion, thromboxane A2 production had stabilized at about twofold the basal value in both the transplanted and in the sham-operated group. Four to eight hours after reperfusion, prostacyclin production reached 15 times the basal value in the transplanted group and twofold in the sham-operated group, the difference being significant (p < 0.05). Twenty to twenty-four hours after reperfusion, prostacyclin production was 18-fold the basal value in the transplanted group and sevenfold in the sham-operated group. No correlation was found between the thromboxane or prostacyclin production and the pulmonary vascular resistance or the mean pulmonary arterial pressure. CONCLUSIONS: The thromboxane A2 production increased fivefold after lung transplantation, with a concomitant 15-fold increase in prostacyclin synthesis, which might have counteracted the vasoconstrictor effect of thromboxane.

6-Ketoprostaglandin F1 alpha↗
PubMed1995

Implications of the prognostic importance of exercise-induced thromboxane formation in survivors of an acute myocardial infarction.

Thirty-two patients with acute myocardial infarction performed an exercise stress test one month after hospital discharge. The in vivo formation of thromboxane and prostacyclin formation before and during the exercise stress test was analyzed with gas chromatography-mass spectrometry of the in vivo formed metabolites 2,3-dinor-TxB2 and 2,3-dinor-6-keto-PGF1 alpha. Patients with a significant increase in thromboxane formation (> 30%) during exercise (P < 0.0001) had a worse prognosis, with a 60% incidence of coronary events during the three years following the index infarction as compared to only 8% in the group without such an increase in thromboxane formation during exercise (P = 0.008). The group with coronary events and increased thromboxane formation included patients not detected by classical risk factors. Our findings suggest that exercise-induced thromboxane formation in survivors of an acute myocardial infarction may include prognostic information not defined by other risk indicators.

6-Ketoprostaglandin F1 alpha↗
PubMed1992

Evidence of increased platelet activation after thrombolysis in patients with acute myocardial infarction.

OBJECTIVE: To assess platelet activation after thrombolysis in patients with acute myocardial infarction. DESIGN: Platelet function was assessed by measurement of the in vivo synthesis of thromboxane by gas chromatography-mass spectrometry of thromboxane's major urinary metabolite, 2,3-dinor-thromboxane-B2. SETTING: Coronary care unit of Huddinge University Hospital. SUBJECTS: 30 patients with acute myocardial infarction given either streptokinase 1.5 million units intravenously over one hour + 500 mg aspirin (n = 10), 500 mg aspirin (n = 10), or neither thrombolysis nor aspirin (n = 10). RESULTS: Patients treated by thrombolysis had a 20-fold increase in thromboxane formation during thrombolysis compared with control patients not treated by thrombolysis (p = 0.0001). Until two days after thrombolysis thromboxane production in patients treated with streptokinase did not decrease to a value comparable with patients treated with aspirin but not given thrombolysis. CONCLUSION: Thromboxane production increased considerably during thrombolysis, possibly reflecting greatly enhanced platelet activation. The slow decrease in thromboxane formation after treatment with aspirin suggests that the efficacy of thrombolysis might be improved by more efficient antiplatelet treatment.

Adult↗
PubMed1991

Prostacyclin production in myocardial infarction in the acute phase and during follow-up.

Twenty-five patients with myocardial infarction were monitored in the acute phase and during follow-up with regard to the in vivo production of prostacyclin (PGI2) and thromboxane (TxA2), by measurement of their major urinary metabolites, 2,3-dinor-6-keto-PGF1 alpha and 2,3-dinor-TxB2, respectively. In 22 of these patients PGI2 and TxA2 production were also assessed before, during and after an exercise test performed 6 weeks after discharge. In approximately 24% of patients the in vivo production of prostacyclin did not increase during the acute phase of the infarction process. This inability was usually associated with a decrease in the release of heart muscle enzymes, and was mostly frequently observed in women. During the exercise tolerance test, none of the patients showed any increase in prostacyclin production, in contrast to healthy volunteers, in whom a significant increase was seen. There were no differences between patients with and without an increase in prostacyclin production during the acute phase. At the follow-up 2 years after the myocardial infarction, eight cardiac events had occurred, all of which were noted among patients who exhibited an expected increase in prostacyclin production in association with the infarction. This would seem reasonable, since most of the patients in this group had larger primary infarctions.

6-Ketoprostaglandin F1 alpha↗
PubMed1991

Effects of non-steroidal anti-inflammatory drugs on the in vivo synthesis of thromboxane and prostacyclin in humans.

Most NSAIDs seem to have inhibitory effects on the in vivo synthesis of both TxA2 and PGI2. However there are large differences in the duration of the inhibitory effects as shown in the table below. Aspirin, indomethacin, naproxen and piroxicam inhibit the second wave of platelet aggregation. This effect on platelet aggregation persists as long as each drug causes inhibition of TxA2 synthesis. Thus, inhibition of TxA2 synthesis is likely to be the reason for the effect of NSAIDs on platelet function. The lack of effect of paracetamol on TxA2 synthesis together with the lack of effect on platelet aggregation by paracetamol are in further support of this. [table: see text]

Acetaminophen↗
PubMed1990

Thromboxane synthase inhibition: "endoperoxide shunt phenomenon" does not occur in healthy humans in vivo.

The effects of the thromboxane synthase inhibitor CGS13080 on the in vivo synthesis of thromboxane and prostacyclin were determined in six healthy volunteers. Two different doses (0.08 and 0.25 mg/kg x h) were infused for six hours under strictly controlled conditions and 2,3-dinor-TxB2 and 2,3-dinor-6-keto-PGF1 alpha were measured in urine using gaschromatography--mass spectrometry. The in vivo synthesis of thromboxane was inhibited by 80-75% while there was no effect on the in vivo prostacyclin synthesis.

6-Ketoprostaglandin F1 alpha↗
PubMed1990

Increased thromboxane formation in patients with antiphospholipid syndrome.

Thirty-one patients with IgG antibodies to cardiolipin (ACLA) were studied to determine their in vivo formation of the platelet aggregating and vasoconstricting substance thromboxane A2 (TxA2) and the platelet inhibiting and vasodilating substance prostacyclin (PGI2). This was done by measurements in urine of their enzymatically formed metabolites 2,3-dinor-TxB2 and 2,3-dinor-6-keto-PGF1 alpha, respectively, using gas chromatography-mass spectrometry. It is demonstrated that patients with IgG ACLA have a highly significant increase in the biosynthesis of TxA2 compared with age-matched healthy controls (807 +/- 163 [SEM] vs. 230 +/- 15 pg mg-1 creatinine, P = 0.0000005). A significant increment of the formation of PGI2 was also found (189 +/- 23 (SEM) vs. 125 +/- 11 pg mg-1 creatinine, P = 0.03), although this was much less pronounced than that for TxA2. We conclude that the highly increased formation of TxA2, reflecting platelet activation, in patients with IgG ACLA is of pathophysiologic relevance for their tendency to arterial and venous thrombosis and hence that they should be considered for prophylactic treatment with inhibitors of TxA2 formation, like aspirin.

Adult↗
PubMed1989

Effects of naproxen on the in vivo synthesis of thromboxane and prostacyclin in man.

The effect of a single oral dose of 500 mg naproxen on the synthesis in vivo of thromboxane A2 and prostacyclin was studied in healthy volunteers. The synthesis of the prostanoids was assessed by measuring the urinary excretion of the metabolites 2,3-dinor-TxB2 and 2,3-dinor-6-keto-PGF1 alpha, respectively, using stable isotope dilution assays based on gas chromatography - mass spectrometry. Naproxen caused significant inhibition of the excretion of both metabolites for about two days. The reduction of the thromboxane metabolite was more pronounced (75% inhibition) than that of the prostacyclin metabolite (about 50% inhibition). The data support the idea that naproxen causes reversible inhibition of cyclooxygenase.

6-Ketoprostaglandin F1 alpha↗
PubMed1989

An increase in the ratio of thromboxane A2 to prostacyclin in association with increased blood pressure in patients on cyclosporine A.

The aim of this study was to determine the effect of two years of treatment with cyclosporine A on blood pressure and the rates of secretion into the circulation of the vasoconstrictor thromboxane A2 and the vasodilator prostacyclin. Seven patient suffering from multiple sclerosis took part. Their blood pressures and urinary concentrations of 2,3-dinor-thromboxane A2 (a major urinary metabolite of thromboxane A2) and of 2,3-dinor-6-keto-prostaglandin F1 alpha (the major urinary metabolite of prostacyclin) were determined at the end of two years of treatment with cyclosporine A, and once again three months after cessation of this treatment. No other drugs were given during or after cyclosporine A. Mean arterial blood pressure was 113 +/- 5 mmHg (mean +/- SEM) during the cyclosporine A treatment, but fell to 94 +/- 4 mmHg after the three-month's wash-out period. Urinary excretion of the thromboxane metabolite decreased slightly from 674 +/- 150 pg.mg-1 creatinine during cyclosporine A therapy to 503 +/- 90 pg.mg-1-creatinine after the end of therapy. At the same time the prostacyclin metabolite increased significantly from 82 +/- 17 pg.mg-1 creatinine to 113 +/- 23 pg.mg-1 creatinine (P less than 0.05). The ratio of 2,3-dinor-thromboxane B2 to 2,3-dinor-6-keto-prostaglandin F1 alpha (taken as a measure of vasoconstrictor prostanoid activity) fell significantly from 8.4 +/- 0.8 4.7 +/- 0.6 (P less than 0.005). The shift in prostanoid production observed during cyclosporine A treatment could be one causal factor for the hypertensive and thromboembolic events associated with the use of this drug.

6-Ketoprostaglandin F1 alpha↗
PubMed1989

In vivo biosynthesis of thromboxane and prostacyclin during exposure to physiological levels of epinephrine.

The effects of 20-min epinephrine infusion (0.025 and 0.3 nmol/kg/min) on the in vivo synthesis of thromboxane A2 and prostacyclin were studied in ten healthy male volunteers. We assessed the in vivo biosynthesis of thromboxane A2 and prostacyclin by measurement of the urinary metabolites 2,3-dinor-TxB2 and 2,3-dinor-6-keto-PGF1 alpha, respectively. Epinephrine infusion did not cause any significant changes in the urinary excretion of the two metabolites. Thus, we conclude that physiological levels of epinephrine do not affect the in vivo biosynthesis of thromboxane A2 and prostacyclin.

Adult↗
PubMed1989

The effect of arachidonic acid and its metabolites on acid production in isolated human parietal cells.

The effect of arachidonic acid and its metabolites on the histamine-stimulated acid production in human isolated parietal cells provenient from endoscopic biopsies was examined. 14C-aminopyrine (14C-AP) accumulation in the parietal cells was used for evaluation of acid production. Histamine dose-dependently increased AP uptake. Histamine stimulation (taken as 100% at 10(-5) M) was significantly inhibited by prostaglandin (PG) E2 to 66 +/- 7% at 10(-8) M, 42 +/- 8% at 10(-6) M, and 13 +/- 10% at 10(-4) M (mean +/- SEM, n = 10). PGF2 alpha, PGD2, and PGI2 showed significant inhibitory effects only at very high concentrations (10(-5)-10(-4) M). Leukotriene (LT) B4 and LTC4 were without effect. The basal acid production (taken as 0%) was lowered significantly by 10(-6) M arachidonic acid to -20 +/- 7.4% (p less than 0.02, n = 10), and the histamine-stimulated (10(-6) M) acid production from 100% to 64 +/- 7.2% (p less than 0.001, n = 10). Aspirin (10(-3) M) increased basal (45 +/- 9.6%, p less than 0.001, n = 10) and histamine-stimulated (10(-6) M) acid production (164 +/- 16.3%, p less than 0.001). It is concluded that PGE2, the major product from arachidonic acid metabolism in the human gastric mucosa, is a significant inhibitor of the histamine-stimulated human parietal cell and may, in humans, play a role as a local physiologic inhibitor of acid secretion.

Adult↗
PubMed1989

Drug interactions with the in vivo synthesis of thromboxane and prostacyclin.

The biosynthesis and metabolic degradation of thromboxane and prostacyclin are briefly described with particular emphasis on the peculiarities of the enzymes involved. This is of great importance for the understanding of this system and for proper interpretation of experimental data. The requirements for adequate methodology in studies designed to assess the in vivo synthesis of those prostanoids are discussed. The characteristics of the thromboxane-prostacyclin system in normals are presented in detail with particular emphasis on those facets of importance for interpretation of literature data, like the diurnal variation, the large interindividual variation etc. The present status of knowledge about the involvement of this system in various cardiovascular diseases as well as the interaction of drugs of various types with the in vivo synthesis of those prostanoids is reviewed in detail.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1988

Effects of intermittent treatment with aspirin on thromboxane and prostacyclin formation in patients with acute myocardial infarction.

Thromboxane and prostacyclin formation were monitored in twenty patients with acute myocardial infarction. Ten received 500 mg acetylsalicylic acid (ASA) orally starting 12 h after admission and then intermittently every third day for one month; the other ten did not receive ASA or any other drug known to interfere with the synthesis of prostanoids. In the ASA group thromboxane formation, initially raised, fell rapidly and remained low. In the control group thromboxane formation decreased very slowly and was not normal by the end of the study period. Prostacyclin formation seemed identical in the two groups. Thus intermittent ASA, in this dosage, efficiently inhibited the enhanced thromboxane formation in acute myocardial infarction without interfering with prostacyclin formation.

Administration, Oral↗