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Biomedical subjects

U Abildgaard

Publications and source records attributed to U Abildgaard.

At least 73 records · Page 4Linked to original sources
PubMed1992

Renal function in patients with untreated acute myocardial infarction.

This study provides data on plasma volume (PV), extracellular volume (ECV) and renal function in 8 untreated patients with acute myocardial infarction (AMI). At day 2 and day 10 after AMI, glomerular filtration rate (GFR), urinary excretion rate of water (Vu), sodium clearance (CNa) and lithium clearance (CLi) were used for assessing reabsorption rates of sodium and water in proximal and distal nephron segments. PV and blood pressure at day 2 were not significantly different from values at day 10. Heart rate (HR), weight and ECV at day 2 were significantly increased when compared with values at day 10 (78 vs. 62 pr. min and 17.0 vs. 16.2 1, respectively). Plasma norepinephrine values were slightly elevated at day 2 and day 10. GFR was initially high and decreased from day 2 to day 10 (118 vs. 104 ml min-1) together with CLi and Ck. However, Vu, CNa and fractional excretion rate of sodium increased markedly from day 2 to day 10. The results suggest that sodium and water retention in the initial phase of AMI without left ventricular failure is due to an increase in tubular reabsorption in distal nephron segments mediated by mechanisms other than the sympathetic nervous system.

Absorption↗
PubMed1992

The present status of tissue factor pathway inhibitor.

Tissue factor pathway inhibitor (TFPI) is the factor Xa-dependent inhibitor of the factor VIIa/tissue factor complex. The plasma concentration of this 276 amino acid, 40 kDa glycoprotein is normally about 100 ng/ml. There are three intravascular pools of TFPI: 50-90% is on the endothelium, 10-50% is in plasma and less than 2.5% is in platelets. The TFPI in plasma is mainly associated with lipoproteins-only about 5% is free TFPI. The lipoprotein-associated TFPI seems to be of less anticoagulant effect than the free TFPI. Both unfractionated heparin, low-molecular-weight heparins and pentosan polysulphate induce release of TFPI after intravenous injection, whereas dermatan sulphate does not. The interactions with TFPI account for a considerable amount of the anticoagulant effect of heparin. Studies have shown increased TFPI levels in plasma from patients with advanced malignancy and in subjects with fatal DIC or septicaemia. The reason for this is unknown. For measuring the anticoagulant activity of TFPI in plasma, end-point or antigen assays may be less useful than the clotting assay with dilute tissue factor. Animal studies indicate that the main physiological role of TFPI is the inhibition of small amounts of tissue factor. TFPI is probably essential for a normal haemostatic balance.

Disease↗
PubMed1991

Safety of high doses of low molecular weight heparin (Fragmin) in acute myocardial infarction. A dose-finding study.

We postulated that low molecular weight heparin (LMWH) in doses producing plasma levels in the range of 0.6-1.0 anti-Xa U/ml may reduce the incidence of left ventricular thrombi (LVT) secondary to acute anterior wall myocardial infarction (AAMI). In an open, dose-finding study, 72 patients with acute myocardial infarction (AMI) were treated with Fragmin (KABI) 240-360 anti-Xa U/kg/24h subcutaneously for 6-10 days. 300 anti-Xa U/kg/24h given as 2 or 3 injections resulted in a mean plasma concentration of about 0.8 anti-a U/ml. There were 3 minor haemorrhages, all in a subgroup of 22 patients also being treated with 0.3 g aspirin orally per day after 1.5 mill. U streptokinase intravenously on admission. In the 38 patients with AAMI receiving 300 anti-Xa U/kg/24h there were only 3 LVT during the period of treatment (8%). In conclusion, 300 anti-Xa U Fragmin/kg/24h s.c to patients with AMI appears safe, but minor haemorrhage may occur in patients receiving aspirin concomitantly. Although these data are limited, the low incidence of LVT in patients with AAMI suggests efficacy of this dose of Fragmin to prevent LVT.

Adult↗
PubMed1991

[Treatment of deep venous thrombosis with low molecular weight heparin (Fragmin)].

At our department, the routine treatment of deep venous thrombosis is low molecular weight heparin (Fragmin) in doses of 80-120 anti-Xa Units/Kg body weight/12h subcutaneously. In an open study we found that anti-thrombotic efficacy of the treatment, and safety with regard to bleeding, was the same as found in controlled studies. The patient population was characterized by old age and high morbidity. Nevertheless, eight out of 30 patients (26%) could be transferred to ambulant care on day 2-4. We conclude that low molecular weight heparin facilitates out-patient care of uncomplicated cases of deep venous thrombosis.

Adult↗
PubMed1991

The anticoagulant effect in heparinized blood and plasma resulting from interactions with extrinsic pathway inhibitor.

The influence of Extrinsic pathway inhibitor (EPI) on global clotting times of plasma was studied using activity-blocking IgG antibodies. Dilute tissue thromboplastin (TP) clotting times in plasma collected after intravenous injection of heparin were dramatically shortened by the addition of anti-EPI IgG. Anti-EPI IgG shortened the TP times to a lesser degree in plasma heparinized in vitro. Compared to plasma heparinized in vitro, the TP clotting times were markedly prolonged in post-heparin plasma of equal heparin concentration. Addition of anti-antithrombin IgG reduced the clotting times somewhat more than did anti-EPI IgG, particularly in normal plasma. In plasma from patients with cancer, about equal effect was obtained by blocking either EPI or antithrombin. These clotting time studies suggested that much of the anticoagulant effect caused by injection of heparin depended on EPI. This was confirmed by recording the release of fibrinopeptide A (FPA), as marker of thrombin generation, following addition of TP and CaCl2 to citrated blood. Thrombin generation was delayed and markedly reduced in post-heparin blood compared to that in normal blood. After incubating post-heparin citrated blood with anti-EPI IgG, the generation of FPA was more rapid; the amounts released 30 seconds after addition of TP were 6 times greater (36 vs 6 ng/ml) than in post-heparin blood without anti-EPI IgG. The subsequent FPA values were midway between pre-injection and post-heparin values. In conclusion, between one third and one half of the inhibition of TP-initiated coagulation in post-heparin plasma depends on EPI. This inhibition is mainly due to inactivation of the factor VIIa-TP complex. A small, but distinct contributing effect observed in the APTT assay (and hence no TP) indicates that even increased inactivation of activated factor X contributes. In cancer patients, these EPI-heparin interactions contribute even more to the anticoagulant effects of heparin.

Antithrombins↗
PubMed1991

Alpha-1 blockade inhibits compensatory sodium reabsorption in the proximal tubules during furosemide-induced volume contraction.

The renal effects of alpha-1 adrenoceptor blockade (i.v. infusion of doxazosin, 50 micrograms/kg prime; 30 micrograms/kg/h) on tubular sodium reabsorption during acute furosemide-induced volume contraction (i.v. infusion of furosemide, 7.5 mg/kg/h for 3 h) was investigated by clearance technique in conscious rats. By measuring inulin clearance, lithium clearance and urinary excretion rates of sodium and water, the changes in proximal and distal tubular sodium handling were dissociated. In furosemide-infused rats given doxazosin (n = 11) or volume replacement (n = 9), the fractional lithium excretion increased from 30% (control) to a steady-state value of 51% (last hour of furosemide infusion), whereas in rats infused with furosemide only (n = 9), the fractional lithium excretion increased transiently to a peak value of 52% and then declined to a steady-state value of 39%. Doxazosin attenuated the acute natriuretic response to furosemide by 54%, mainly due to increased sodium reabsorption in the distal nephron segment. This effect was associated with a significant lower mean arterial pressure compared with rats given furosemide only. The results are compatible with a contributory role of proximal tubular alpha-1 adrenoceptors in mediating compensatory Na reabsorption during furosemide-induced volume contraction.

Adrenergic alpha-Antagonists↗
PubMed1991

Extrinsic pathway inhibitor (EPI) released to the blood by heparin is a more powerful coagulation inhibitor than is recombinant EPI.

EPI released to the blood after injection of heparin, as well as recombinant EPI (r-EPI) added to normal plasma prolonged both the dilute Tissue Thromboplastin (TTP) time and the Activated Partial Thromboplastin Time (APTT). It is known that EPI inhibits both factor Xa and the factor VIIa-TTP complex. The prolongation of the APTT by EPI reflects only its inhibition of factor Xa. Addition of anti-EPI immunoglobulins (IgG) to normal plasma shortened the dilute TTP time 7.3 seconds (p less than 0.001) and the APTT by 0.7 seconds (p less than 0.001). In postheparin plasma, with polybrene added to neutralize the direct effect of heparin, the TTP was about 26 seconds longer and the APTT about 9 seconds longer than baseline values. These effects were completely abolished by anti-EPI IgG, as were the effects of r-EPI. The EPI activity (chromogenic substrate-assay) of this postheparin plasma was 1.7 U/ml. The EPI activity of the plasma spiked with r-EPI to obtain comparable effects on clotting were much higher; about 22 U/ml for the TTP effect and about 5 U/ml for the APTT effect. The findings indicate that r-EPI is considerably less potent than postheparin EPI as inhibitor of plasma coagulation. This is most striking when coagulation is initiated through the extrinsic pathway. Possibly, the anticoagulant effect of r-EPI mainly depends on its Xa inhibitory effect.

Blood Coagulation Tests↗
PubMed1991

Involvement of the extrinsic pathway in the activities of low molecular weight heparins.

Anticoagulant effects of the three LMW heparins (LMWHs) Enoxaparine, Fragmin, Logiparin and of unfractionated heparin (UFH) were compared. The heparins were added to plasma to nominal concentration of 0.2 and 0.5 anti XaU/ml plasma. Dilute tissue thromboplastin (TTP) and CaCl2 were added to platelet poor plasma (PPP), platelet rich plasma (PRP) and citrated blood. Thrombin activity was recorded with chromogenic substrate. In PPP, UFH was definitely more inhibitory than LMWH. In PRP, 0.2 U/ml of LMWHs were about as effective as UFH. At 0.5 U/ml PRP, UFH and Logiparin were more effective than Enoxaparine and Fragmin. Factor XII deficient plasma was very sensitive to heparin, and UFH and Logiparin were again more inhibitory. In whole blood, fibrinopeptide A determinations showed that UFH was more inhibitory than LMWH. We conclude that the net anticoagulant effects of these heparins result from interactions with platelets in addition to accelerated inactivation of clotting factors. The in vivo anticoagulant effect of these drugs can therefore not be predicted from their nominal anti Xa and anti IIa effects alone.

Blood Coagulation↗
PubMed1991

Extrinsic pathway inhibitor (EPI) and the post-heparin anticoagulant effect in tissue thromboplastin induced coagulation.

It is known that the anticoagulant effect of blood or plasma is greater when heparin is given in vivo than when added in similar heparin concentrations in vitro. In this study, we neutralized heparin in citrated blood with polybrene, and then triggered coagulation with dilute tissue thromboplastin (TTP) and CaCl2. The clotting time was longer and the release of fibrinopeptide A (FPA) was retarded in the post injection samples compared to samples spiked with heparin in vitro. We have earlier reported that the extrinsic pathway inhibitor (EPI) is released to the blood after heparin injection. This was demonstrated here also for LMW heparin Enoxaparine both after intravenous and subcutaneous administration. Polyclonal blocking antibodies to EPI were added to blood or plasma heparinized in vivo or in vitro, and the direct heparin effect was neutralized with polybrene. When TTP and CaCl2 now were added and clotting time and the release of FPA recorded, the postheparin effect was greatly reduced by the antibodies. Addition of EPI antibodies to post-heparin plasma samples from cancer patients caused a marked reduction in the thromboplastin clotting times. We conclude that the release of EPI to the blood contributes significantly to the anticoagulant effect of heparin ex vivo.

Antibodies↗
PubMed1991

Effects of Felodipine on the dog kidney: a lithium clearance study.

This study was performed in order to investigate the possible influence of sympathetic nerve activity on the effects of the dihydropyridine calcium antagonist felodipine on absolute and fractional reabsorption rates of sodium and water in proximal and distal tubular segments in the dog kidney. Clearance of 51Cr-EDTA was used as a measure of glomerular filtration rate (GFR). GFR, urinary excretion rates of sodium and water, and lithium clearance (C-Li) were used for assessing the absolute and fractional tubular reabsorption rates. Felodipine infusion into the right renal artery increased renal vascular conductance (renal blood flow divided by renal arteriovenous pressure gradient) significantly (by 9%) while GFR remained unchanged. Calculated absolute proximal reabsorption rates remained unchanged while distal sodium reabsorption rate increased significantly from 2.1 +/- 0.3 to 2.7 +/- 0.4 mmol min-1. Sodium clearance (C-Na) increased from 0.22 +/- 0.08 to 0.40 +/- 0.07 ml min-1. The alpha-adrenergic blockade with phentolamine did not affect renal haemodynamic or excretory variables, nor did it influence the haemodynamic response to felodipine. After alpha-adrenergic blockade felodipine caused an increase in C-Na from 0.28 +/- 0.06 ml min-1 to 0.63 +/- 0.04 ml min-1, which was significantly greater than that measured after felodipine alone. The distal load (C-Li) was not significantly different from that obtained after felodipine alone, but distal sodium reabsorption rate increased less significantly after alpha-adrenergic blockade. The results suggest that felodipine, by its effect on tubular flow and/or composition, activates local alpha-adrenergic reflex mechanism(s), which stimulates distal sodium reabsorption, thereby attenuating the natriuretic effect.

Absorption↗
PubMed1991

Tissue factor pathway inhibitor with high anticoagulant activity is increased in post-heparin plasma and in plasma from cancer patients.

This study was performed in order to separate plasma fractions of tissue factor pathway inhibitor (TFPI) on the basis of TFPI's heparin binding properties. A main goal was to look for differences in anticoagulant effect of the TFPI fractions from plasma. Normal plasma and plasma with increased amounts of TFPI were used; plasma from cancer patients and post-heparin plasma (plasma drawn 5 min after heparin injection). Heparin affinity chromatography separated plasma TFPI into four fractions with increasing heparin affinity: the flow-through fraction, a low affinity fraction eluting at less than 0.3 M NaCl, an intermediate affinity fraction eluting at 0.3-0.55 M NaCl and a high affinity fraction eluting at 0.55-1.0 M NaCl. These fractions corresponded partly to the three TFPI activity fractions obtained by gel filtration. In plasma from cancer patients, the two fractions with intermediate and high heparin affinity were increased three- to four-fold, compared to normal plasma. The TFPI activity in these two fractions eluted with low-molecular-weight (35-60 kD) on gel filtration. In post-heparin plasma an even larger increase in the fraction with high heparin affinity was found; compared to that in normal plasma it was increased 14-fold. TFPI was purified to 0.72 U/mg protein in this fraction (about 43-fold compared to normal plasma TFPI). The anticoagulant effect of TFPI, relative to the chromogenic substrate TFPI activity, was greater in plasma fractions with high heparin affinity than in the other plasma TFPI fractions, and it was five-fold greater than the anticoagulant effect of recombinant TFPI. Thus, plasma TFPI is heterogenous in heparin affinity and in anticoagulant potency.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Atrial fibrillation and left atrial enlargement: cause or effect?

In a blinded controlled study, 58 consecutive patients with definite left atrial enlargement (M-mode dimension of at least 45 mm) were followed up after 1-2 years. The aim of the study was to examine the following: (a) the prospective risk of developing atrial fibrillation (AF); and (b) the effect of the heart rhythm on the left atrial size. Of 36 patients in sinus rhythm, one developed paroxysmal AF and one developed persistent AF during a median follow-up period of 20 months. Thus the incidence of new AF was 5% per year. Eighteen patients died before scheduled echocardiographic follow-up, but in the remaining subjects the left atrial dimension did not change significantly: the median increment was 1 mm in 20 patients who sustained sinus rhythm vs 2 mm in 16 patients with chronic AF (P greater than 0.05). Although left atrial dilatation may cause AF and vice versa, this study demonstrated that the incidence of new AF is low, despite the fact that the left atrial dimension is substantially increased. Similarly, AF per se does not appear to have any major impact on the left atrial dimension.

Adult↗
PubMed1991

Extrinsic pathway inhibitor--the key to feedback control of blood coagulation initiated by tissue thromboplastin.

Extrinsic pathway inhibitor (EPI) is a Kunitz type serine protease inhibitor. EPI is a potent inhibitor of the factor VIIa/thromboplastin (TP) complex in the presence of factor Xa and is also a direct inhibitor of factor Xa. The inhibitory mechanism is complex and is currently thought to involve, in a first step, the formation of a EPI-factor Xa complex, and, in a second step, the formation a quaternary EPI-factor Xa-factor VIIa-TP complex. In the blood vessels, EPI is confined to three different pools. A major pool of EPI is bound to the endothelial surface, and this fraction may be released by heparin. Plasma contains a second, but smaller pool of EPI (approximately 10-50% of the endothelial surface pool) at a concentration of 50-100 ng/ml. This pool consists mostly of EPI-lipoprotein complexes and only less than 10% is carrier-free EPI. A third pool of EPI is confined to platelets (less than 10% of the plasma pool). The biological role of these pools has not yet been clarified, but some evidence suggest that the carrier-free EPI is biologically most active. In patients, disseminated intravascular coagulation may continue despite normal or even elevated EPI levels. However, evidence has now been provided to indicate that EPI can inhibit factor VIIa/TP complexes formed in vivo to prevent the effect of limited amounts of TP. Taken together, the present knowledge of EPI indicates that EPI functions as a key inhibitor to feedback control of blood coagulation initiated by TP.

Blood Coagulation↗
PubMed1991

Heparin requires both antithrombin and extrinsic pathway inhibitor for its anticoagulant effect in human blood.

Heparinization of blood inhibited the generation of fibrinopeptide A (FPA) after addition of thromboplastin (TP). Heparinization was more effective when performed in vivo than in vitro; the amounts of FPA at 60 s incubation were 8% and 32%, respectively, of control values in nonheparinized blood. When monospecific, neutralizing IgG against extrinsic pathway inhibitor (anti-EPI) were added to heparinized blood prior to TP, the amount of FPA increased to 65%. When monospecific IgG blocking antithrombin (anti-AT) was used, the amount of FPA increased to values similar to those in nonheparinized blood. When anti-AT and anti-EPI were both added to heparinized blood, FPA was generated about 25% faster than in normal blood. These results show that EPI contributes significantly to the anticoagulant effect of heparin in human blood.

Antibodies, Monoclonal↗
PubMed1991

Chromogenic substrate assay of extrinsic pathway inhibitor (EPI): levels in the normal population and relation to cholesterol.

A two-stage chromogenic substrate assay was standardized to measure extrinsic pathway inhibitor (EPI) activity in plasma and serum samples. In the first stage, diluted plasma or serum (0-0.8%) was incubated with factor VIIa (25 pM), tissue thromboplastin (tissue factor, TF, 1% v/v) with excess binding sites for factor VIIa, and factor Xa (0.8 nM). In the second stage, excess factor X and chromogenic substrate were added as substrate for residual TF/factor VIIa catalytic activity. Heating the samples at 56 degrees C for 15 min before assay removed greater than 95% of the factor VII amidolytic activity of the samples, defibrinated the plasma, and produced only slight reduction of EPI activity. The coefficient of variation for the same sample assayed on different days was 8.7-10.6% and the intra-assay coefficient of variation was 5.0%. Addition of anti-EPI immunoglobulin to normal plasma completely abolished the EPI activity of the sample. EPI activity was stable in plasma samples stored at -20 degrees C, but in serum, some samples lost greater than 50% activity after 3 months at -70 degrees C. Median EPI activity of umbilical cord blood was 45% (range 33-93%). In a cohort of healthy blood donors (n = 176) EPI activity was significantly correlated with age; the regression line was y = 68% + 0.60x (r = 0.39). The approximated standard deviation for the regression line was 17.9% and the age-adjusted reference limits were determined. Equal levels were seen in males and females.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

[Local, central and regional functions. Obsolete concepts?].

As a consequence of the regionalization of the health services in Norway hospitals were given either local, central or regional responsibility. This system was intended to improve the availability of expertise and costly equipment, and at the same time reduce the growth of expenditures on health care. In the last few years, however, many of the smaller hospitals have improved their technical and medical skills to such an extent that this classification system has become less meaningful. Aker hospital in Oslo carries out local, central and regional functions. In a prospective study at this hospital we found that 88% of 980 consecutive medical admissions could be classified as local hospital admissions. Only 5% of the patients needed service at the central level, and 5% at the regional level. In our opinion it would suffice to have two types of hospital ("treatment levels"), standard hospitals and referral hospitals.

Hospitals, County↗