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Biomedical subjects

O Vesterqvist

Publications and source records attributed to O Vesterqvist.

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

Immediate effects of heparin and LMW heparin on some platelet and endothelial derived factors.

Heparin and a low molecular heparin fragment, injected intravenously in volunteers, increased the plasma concentrations of platelet factor 4, but did not induce platelet activation as judged from excretion of 2,3-dinor-TxB2 (a major thromboxane A2 metabolite) and beta-thromboglobulin (btg) in urine and from btg levels in plasma. Heparin prolonged, within the normal range, the bleeding time in all six subjects. Platelet aggregation in platelet rich plasma was potentiated by both heparins, but platelet number, mean platelet volume and platelet distribution width were not affected. No evidence for endothelial release of prostacyclin was obtained as judged from urinary excretion of 2,3-dinor-6-keto-PGF1 alpha (a major prostacyclin metabolite), and plasma concentrations of tissue plasminogen activator, its inhibitor (PAI-1) and the von Willebrand-factor were unchanged.

Adult↗
PubMed1988

Development of a vaginal gel containing 9-deoxo-16,16-dimethyl-9-methylene PGE2 for cervical dilatation and pregnancy termination.

A stable hydrophilic gel for vaginal administration containing 9-deoxo-16,16-dimethyl-9-methylene PGE2 (9-methylene PGE2) was developed and its clinical usefulness for preoperative cervical dilatation and for termination of first and second trimester pregnancy evaluated in 521 pregnant patients admitted to the hospital for therapeutic abortion. Following vaginal administration of 3 mg of 9-methylene PGE2 gel a peak plasma level of between 3.5 and 10 ng/ml was found 3 to 6 hours following treatment. The "bioavailability" of the drug was in the order of 25-30%. 9-methylene PGE2 was found to be equally effective as 1 mg Cervagem for preoperative cervical dilatation. With a pretreatment period of 3 hours side effects were rare with both compounds. If the pretreatment period was extended to 12 hours the degree of cervical dilatation, but also the frequency of side effects increased significantly. Repeated administration of 9-methylene PGE2 was found to be effective (96% complete abortion) in terminating very early pregnancy provided the total dose was 10 mg or more. During second trimester the minimum effective dose was 4.5 mg of the compound repeated every fourth hour. The results of the present study have shown that with the new gel formulation the amount of 9-methylene PGE2 needed to terminate first and second trimester pregnancy was approximately ten times less in comparison with the previously used lipid base suppositories. The treatment was also associated with a low frequency of side effects.

16,16-Dimethylprostaglandin E2↗
PubMed1988

Urinary metabolites of thromboxane and prostacyclin in diabetes mellitus.

The in vivo synthesis of thromboxane A2 and prostacyclin was estimated in 23 diabetics through measurements of the major urinary metabolites 2,3-dinor-thromboxane B2 and 2,3-dinor-6-keto-PGF 1 alpha utilizing gas chromatography-mass spectrometry. Mean excretion was similar to that in non-diabetic subjects. The possible influence of hyperglycemia on the excretion of 2,3-dinor-thromboxane B2 and 2,3-dinor-6-keto-PGF 1 alpha was evaluated in three ways: by measuring excretion before and during an acute 9-h normalization of hyperglycemia through an artificial pancreas (Biostator) as well as by comparing excretion before and 7-12 days or 40-180 days after the initiation of insulin treatment. Despite significant reducing effects on hyperglycemia or on levels of hemoglobin A 1c, no effects on the excretion of the thromboxane and prostacyclin metabolites could be found. Abnormal formation of thromboxane or prostacyclin is not a generalized feature of the diabetic state.

6-Ketoprostaglandin F1 alpha↗
PubMed1988

Measurements of the in vivo synthesis of thromboxane and prostacyclin in humans.

Our studies on the urinary excretion of 2,3-dinor-TxB2 and 2,3-dinor-6-keto-PGF1 alpha in humans strongly indicate that these metabolites are good indicators of the in vivo synthesis of TxA2 and PGI2. Our finding that physical exercise increases PGI2 synthesis was of particular importance for the design of adequate studies on the effects of various drugs on the in vivo formation of PGI2. The rapid recovery (within 3-4 h) of PGI2 formation found following administration of 1.0 g of aspirin together with the long-lasting inhibition of TxA2, suggests that in the prophylaxis of thromboembolic events an intermittent dosage of 0.5 g of aspirin every third day should be a better alternative than daily low or high doses of aspirin. The increased TxA2 formation found in patients with acute myocardial infarction, deep vein thrombosis and in patients following insertion of synthetic surfaces into the circulation, is very likely a reflection of an increased activation of platelets. The increased TxA2 synthesis may cause further platelet activation, vasoconstriction and activation of the coagulation system. Thus, theoretically, inhibition of TxA2 could diminish platelet activation and reduce the risk of thrombotic complications. It is well known that the interaction between platelets and the vessel wall plays an important role in haemostasis and in the development of thrombosis. On the basis of its biological properties, PGI2 may play a local haemostatic role in the regulation of this interaction. Our studies of myocardial infarction and deep vein thrombosis clearly demonstrate the involvement of PGI2 in those diseases.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1988

In vivo production of thromboxane and prostacyclin in patients following total hip arthroplasty.

The in vivo production of thromboxane and prostacyclin was studied by measurements of their major urinary metabolites in eight patients undergoing total hip arthroplasty. Specific methods based on gas chromatography-mass spectrometry were used to measure the urinary excretion of 2,3-dinor-TxB2 and 2,3-dinor-6-keto-PGF1 alpha. The excretion of these metabolites increased about 10-fold during the intra and immediate postoperative period and 4 days after surgery was still higher than during the preoperative period. The increased thromboxane formation reflects probable activation of platelets whereas the increased prostacyclin could be part of a vascular defense against induced thrombotic activity. These findings may have pathophysiological implications.

6-Ketoprostaglandin F1 alpha↗
PubMed1987

Hemostatic disturbances associated with implantation of an artificial heart.

Coagulation and platelet parameters have been assessed following implantation of a Jarvik 7 artificial heart. Initially an ongoing intravascular coagulation could not be overcome with heparin and coumarin. The in vivo formation of thromboxane A2 (as monitored by measurement of the major urinary metabolite) was increased 3-4 fold. Administration of aspirin every second to third day reduced the thromboxane formation dramatically. In parallel to this, the intravascular coagulation subsided, the demand for heparin decreased considerably and the clinical condition of the patient improved. These events provide evidence for a direct link between thromboxane formation and the coagulation cascade. The thromboxane formation was insufficiently suppressed around the 110th postoperative day. Two weeks later the patient suffered a cerebral embolus, followed by a bleeding in the embolized area. This case illustrates the applicability of antiplatelet treatment when the need for efficient antithrombotic treatment is especially pronounced. Aspirin, however, is not the ideal drug for this purpose.

Blood Coagulation Tests↗
PubMed1987

Thromboxane and prostacyclin formation in patients with deep vein thrombosis.

The urinary excretion of 2,3-dinor-TxB2 and 2,3-dinor-6-keto-PGF1 alpha (the major urinary metabolites of thromboxane B2 and prostacyclin) was measured in ten patients with confirmed deep vein thrombosis, using specific methods based on gas chromatography - mass spectrometry with deuterium-labelled internal standards. Measurements of these major urinary metabolites makes it possible to monitor the in vivo formation of thromboxane A2 and prostacyclin. The results demonstrate an abnormally high and very variable excretion of 2,3-dinor-TxB2 and 2,3-dinor-6-keto-PGF1 alpha in patients with deep vein thrombosis. This indicate that both thromboxane A2 and prostacyclin are involved in the course of events associated with this disease.

6-Ketoprostaglandin F1 alpha↗
PubMed1987

Synthetic arterial grafts cause prolonged increase in the in vivo formation of thromboxane and prostacyclin in humans.

To evaluate the in vivo production of thromboxane A2 and prostacyclin their major urinary metabolites were measured in patients following graft replacement of the abdominal aorta. Specific methods based on gas chromatography-mass spectrometry were used to measure the urinary excretion of 2,3-dinor-TxB2 and 2,3-dinor-6-keto-PGF1 alpha. The excretion of these metabolites increased tenfold and almost fortyfold during post-operative Day 1 and remained elevated 6-10 days p.o. In a group undergoing cholecystectomy smaller changes of shorter duration were seen. It is concluded from this study that synthetic grafts cause prolonged increase in the in vivo formation of thromboxane A2 and prostacyclin. The reason for the increased TxA2 formation is probably platelet interaction with the foreign surface, whereas the increase of PGI2 could be part of a vascular defense against induced thrombotic activity. Those increases may have pathophysiologic implications.

6-Ketoprostaglandin F1 alpha↗
PubMed1986

Rapid recovery of in vivo prostacyclin formation after inhibition by aspirin. Evidence from measurements of the major urinary metabolite of prostacyclin by GC-MS.

The effect of aspirin on the in vivo formation of prostacyclin and thromboxane A2 in normal healthy individuals was studied by measuring the urinary excretion of 2,3-dinor-6-keto-PGF1 alpha and 2,3-dinor-TxB2 by gas chromatography-mass spectrometry. Administration of 500 mg aspirin twice daily caused a sustained reduction in the excretion of 2,3-dinor-TxB2 to 10-15% of the predose value, while the excretion of 2,3-dinor-6-keto-PGF1 alpha was reduced for only about 3 hours after the aspirin dose. The data demonstrate a considerable difference in the inhibitory effect of aspirin on the in vivo synthesis of thromboxane A2 and prostacyclin.

6-Ketoprostaglandin F1 alpha↗
PubMed1986

In vivo production of prostacyclin and thromboxane in patients with acute myocardial infarction.

The in vivo production of prostacyclin and thromboxane was monitored by measuring their major urinary metabolites 2,3-dinor-thromboxane B2 and 2,3-dinor-6-keto-prostaglandin F1 alpha in ten patients with acute myocardial infarction, five on standard treatment and five receiving prostacyclin infusion. During acute myocardial infarction excretion of 2,3-dinor-thromboxane B2 and 2,3-dinor-6-keto-prostaglandin F1 alpha, measured by a gas chromatography-mass spectrometry method with deuterated internal standards, was significantly increased. This indicates that thromboxane and prostacyclin synthesis are increased during the development of acute myocardial infarction. The excretion data for 2,3-dinor-thromboxane B2 showed that after administration of aspirin there was less pronounced and more variable inhibition than expected. Prostacyclin infusion did not markedly affect the excretion of the thromboxane metabolite.

6-Ketoprostaglandin F1 alpha↗
PubMed1985

In vivo production of thromboxane in acute human myocardial infarction: a preliminary study.

Using a specific quantitative method based on gas chromatography-mass spectrometry the urinary excretion of 2,3-dinor-TxB2 was measured in five patients with acute myocardial infarction shortly after the onset of symptoms. The urinary excretion of 2,3-dinor-TxB2 was markedly higher than seen in normals in three of the five patients. This increased excretion of 2,3-dinor-TxB2 during and after the development of myocardial necrosis indicates an involvement of thromboxane A2 in the pathogenesis of at least some cases of acute myocardial infarction.

Aged↗
PubMed1984

Development of a GC-MS method for quantitation of 2,3-dinor-TxB2 and determinations of the daily urinary excretion rates in healthy humans.

Tetradeuterated 2,3-dinor-thromboxane B2 (2,3-dinor-TxB2) of high isotopic purity was prepared. This compound was used as internal standard in the development of a method for quantitation of 2,3-dinor-TxB2 in human urine based on gas chromatography--mass spectrometry with multiple ion detection. The accuracy of the method is about +/- 5% at the levels encountered when urine from normal healthy individuals was analyzed. The daily urinary excretion of 2,3-dinor-TxB2 in twenty normal healthy males and females was 457 +/- 210 (mean +/- SD) and 444 +/- 160 (mean +/- SD) ng/24 hrs respectively. The diurnal and day-to-day variations were found to be relatively small.

Adult↗
PubMed1984

The prostaglandin-analogue-9-deoxo-16,16-dimethyl-9-methylene-PGE2 inhibits the antidiuretic effect of vasopressin (AVP) in the conscious sheep.

The effects of intravenous infusions of the stable prostaglandin analogue 9-deoxo-16,16-dimethyl-9-methylene-PGE2 (9-methylene-PGE2) in a dosage of 10 or 24 micrograms/min were studied in the consicious euhydrated, dehydrated, and hyperhydrated with the simultaneous administration of exogenous arginine vasopressin (AVP), sheep. The infusions decreased urine osmolality and increased urine flow and renal free water clearance. The results indicate that 9-methylene-PGE2 exhibits its diuretic effect by antagonizing the antidiuretic action of AVP. In the hyperhydrated sheep receiving AVP the syndrome of inappropriate antidiuretic hormone release (SIADH) was simulated. As the prostaglandin analogue effectively blocked the antidiuretic effect of the AVP-administration it appears that 9-methylene-PGE2 may play a future role as a diuretic agent, especially in conditions characterized by water retention and dilutional hyponatremia such as SIADH.

16,16-Dimethylprostaglandin E2↗