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Biomedical subjects

J Swedenborg

Publications and source records attributed to J Swedenborg.

At least 55 records · Page 3Linked to original sources

Infusion methods for determination of peripheral resistance: influence of infused medium and back pressure.

It has been suggested that peripheral vascular resistance (PR), measured intraoperatively, can predict the outcome of infrainguinal reconstructions. There is, however, a great deal of variability in design and predictive value with this method, and it is prone to technical difficulties and possible errors. The present study evaluated the influence of the choice of infusion medium and the back pressure on PR as measured by the infusion technique. In a porcine model of experimentally induced stenosis, standard PR (calculated by the pressure difference across the stenosis and the Doppler volume flow) was compared with PR based on infusions of blood or saline solution. With blood as the infusion medium there was a significant correlation between the PR and the standard values (r = 0.795, p = 0.0005), whereas there was no correlation when saline solution was infused (r = 0.067, p = 0.345). Subtracting the back pressure resulted in a slight improvement in the correlations between standard PR and PR measured after infusion of blood but not saline solution. In summary, blood should be used as an infusion medium in methods of PR determination, but the influence of back pressure remains uncertain.

Animals↗

Correlation between peripheral vascular resistance and time to peak flow during reactive hyperaemia.

Earlier studies have proposed that the time to reach peak hyperaemic flux recorded with laser Doppler (tp) is a simple and accurate method of evaluating ischaemic limbs and possibly a method of estimating the peripheral vascular resistance (PR). The aim of this study was to investigate the relationship between the tp and changes in limb vascular resistance caused by arterial stenosis. Forty postocclusive hyperaemia tests with arterial stenoses of different pressure gradients were performed in four pigs. A laser Doppler fluxmeter was used to record postocclusive hyperaemia in the skin of one hind limb. A specially designed tourniquet was used for the arterial occlusion. Proximal and distal to the occlusion level a snare was used to form different grades of stenosis. The PR (mmHg.ml-1.min-1) was either estimated by infusion of a known blood volume into the tested limb over a given time period with simultaneous measurement of pressure or calculated on the basis of measurements of limb blood flow and blood pressure gradients. The tp was closely related to total limb vascular resistance assessed by the blood infusion method (r = 0.83, p < 0.0003) and to the resistance calculated from volume blood flow and intraarterial pressures (r = 0.86, p < 0.0001). This study suggests that the tp accurately reflects limb vascular resistance in an experimental model. Thus tp may be used as a quantitative indicator of overall blood flow impairment, and should be evaluated in patients with lower-limb atherosclerosis.

Animals↗

Little impact of elective surgery on the incidence and mortality of ruptured aortic aneurysms.

Rupture of an abdominal aortic aneurysm is an important cause of death, particularly for men over 60 years of age. The aim of elective surgery for abdominal aortic aneurysms is to prevent future death from rupture of the aneurysm. The present study examines the influence of elective surgery upon the rate of rupture, comparing 1980 when little elective surgery was done and 1989 when considerably more elective surgery was performed in a well defined population. The rate of rupture and death from such a cause was not affected by the increased number of elective operations. It is concluded that the number of operations generally performed is too small to significantly affect the mortality from rupture. In order to decrease this mortality patients with a high risk of rupture should be found and offered elective surgery.

Age Distribution↗

Antithrombin III inhibits thrombin-induced proliferation in human arterial smooth muscle cells.

Thrombin has attracted increasing attention as a possible mitogen for vascular smooth muscle cells in lesion development both after vascular injury and in atherogenesis. In this study, the ability of antithrombin III to inhibit alpha-thrombin-induced DNA synthesis and cell proliferation in human arterial smooth muscle cells was analyzed. We demonstrate a concentration-dependent initiation of DNA synthesis and cell proliferation by alpha-thrombin. This effect was abolished when complex formation with antithrombin III was allowed before thrombin was added to the cell cultures. Addition of alpha-thrombin and antithrombin III simultaneously at the beginning of the incubation period also resulted in an inhibition of thrombin-induced DNA synthesis, but to a lower degree. The inhibitory activity of antithrombin III was enhanced in the presence of heparin, which on its own had no inhibitory effect on thrombin-induced DNA synthesis. In contrast, the mitogenic activity of alpha-thrombin could be inhibited by heparin in the presence of low concentrations of serum. This inhibition was dependent on the presence of antithrombin III in serum, since heparin lacked effect if antithrombin III was depleted from serum by immunoaffinity chromatography. Analysis of the enzymatic activity of thrombin showed that the influence on catalytic activity of thrombin corresponded to the mitogenic activity of thrombin in the presence of heparin, antithrombin III, and serum. The results suggest that the mitogenic activity of thrombin is regulated by antithrombin III. Therefore, antithrombin III may serve dual functions by inhibiting thrombin in the coagulation cascade and by neutralizing its growth-promoting effects on vascular smooth muscle cells.

Antithrombin III↗

Thrombogenicity of the injured vessel wall--role of antithrombin and heparin.

The thrombogenicity of the vessel wall after endothelial denudation is partly explained by an impaired inhibition of thrombin on the subendothelium. We have previously reported that thrombin coagulant activity can be detected on the vessel wall after balloon injury in vivo. The glycosaminoglycans of the subendothelium differ from those of the endothelium and have a lower catalyzing effect on antithrombin III, but inhibition of thrombin can still be augmented by addition of antithrombin III to the injured vessel surface. In this study the effect of antithrombin III and heparin on thrombin coagulant activity on the vessel wall was studied after in vivo balloon injury of the rabbit aorta using biochemical and immunohistochemical methods and thrombin was analysed after excision of the vessel. Continuous treatment with heparin, lasting until sacrifice of the animal, or treatment with antithrombin III resulted in significant reduction of thrombin coagulant activity on the injured aorta. Heparin given only in conjunction with the injury did not prevent thrombin coagulant activity or deposition of fibrin on the surface. The capacity of the injured vessel wall to inhibit thrombin in vitro was improved on aortic segments obtained from animals receiving antithrombin III but not from those given heparin. It is concluded that treatment with antithrombin III interferes with thrombin appearance on the vessel wall after injury and thereby reduces the risk for thrombosis.

Animals↗

Effect of heparin on thrombin inhibition in the microcirculation.

Disappearance of thrombin enzymatic activity was measured during recirculation through the microvasculature in a rat Langendorff heart preparation. This resulted in a 50% loss of thrombin from the recirculating solution. No increased loss of thrombin could be demonstrated if a mixture of antithrombin III and thrombin was recirculated, compared to thrombin alone. If, however, a heparin/thrombin mixture was recirculated, a 90% loss of thrombin could be demonstrated. Pretreating the microvasculature with large amounts of heparin resulted in recovery of antithrombin III in the recirculated heparin solution. At a subsequent recirculation with a heparin/thrombin mixture the loss of thrombin was decreased to the control level, as seen when recirculation with thrombin alone was performed. It is concluded that disappearance of thrombin enzymatic activity from a solution when recirculated through the microcirculation can be considerably increased if recirculated together with heparin, which probably reacts with endogenous antithrombin III on the vessel wall. The disappearance of thrombin in the absence of heparin was, however, unaffected by antithrombin III. The latter finding is compatible with the hypothesis that, in the microcirculation, antithrombin III/glycosaminoglycans play only a minor role for inhibition of thrombin coagulant activity and that thrombin binds mainly to thrombomodulin.

Animals↗

Hyperhomocysteinemia in patients operated for lower extremity ischaemia below the age of 50--effect of smoking and extent of disease.

Moderate hyperhomocysteinemia may be a risk factor for atherosclerotic peripheral vascular disease (PVD). In order to develop PVD at an early age risk factors are more strongly expressed and hyperhomocysteinemia may be one such factor. Homocysteine is derived from methionine and is metabolised by cystathionine-synthase to cystathionine or remethylated to methionine. Cystathionine-synthase activity is dependent on vitamin B6 while the remethylation of homocysteine is dependent on vitamin B12 and folate. The present study analyses homocysteine in patients operated on for lower extremity ischaemia before the age of 50. Homocysteine before and after loading with methionine, vitamin B6, B12 and folate were measured at follow-up. The patients were compared to age- and sex-matched controls. Significantly more patients than controls had hyperhomocysteinemia, 16/58 vs. 4/65, defined as fasting total homocysteine above 18.6 mumol/l. Loading with methionine did not further discriminate between patients and controls. Smoking patients had higher levels of homocysteine than non-smoking patients or smoking and non-smoking controls. Smoking patients also had lower levels of vitamin B6. When comparing patients with suprainguinal, infrainguinal and multilevel disease the highest homocysteine levels were seen in the latter group. Also, in this group smoking patients had higher homocysteine levels. Multivariate analysis revealed that homocysteine was associated with low levels of vitamin B12, folate and smoking. Smoking therefore seems to be connected to increased homocysteine levels in patients with early development of atherosclerosis, partly explained by decreased levels of B6, B12 and folate.

Adult↗

Level of arterial obstruction in patients with peripheral arterial occlusive disease (PAOD) determined by laser Doppler fluxmetry.

AIM: To evaluate the laser Doppler fluxmeter as a non-invasive screening method to determine the level of peripheral arterial occlusive disease (PAOD) in the lower limb. DESIGN: Open study of the veno-arterial reflex (VAR) during a shift in body position using a laser Doppler fluxmeter at five probe positions distal to the knee, compared with the occlusion level determined by arteriography and segmental plethysmography. MATERIALS: 50 legs comprising 10 normal controls, 20 legs with suprainguinal obstructions (10 claudication and 10 critical ischaemia) and 20 legs with infrainguinal obstructions (10 claudication and 10 critical ischaemia). RESULTS: Controls had normal VAR (mean flux reductions of 38% during dependency) at all probe positions. Legs with infrainguinal disease had normal reflexes proximally but significantly disturbed reflexes distally, whereas suprainguinal disease showed alterations at all sites. Claudicants had diminished flux reduction (mean 12%) whilst those with critical ischaemia increased the flux (mean 32%). CONCLUSION: This simple, non-invasive technique may be of use in determining the level of obstruction in PAOD.

Aged↗

Antioxidant treatment inhibits the development of intimal thickening after balloon injury of the aorta in hypercholesterolemic rabbits.

The effect of the antioxidant butylated hydroxytoluene (BHT) on the accumulation of intimal smooth muscle cells (SMC) and development of intimal thickening after balloon catheter injury of the aorta were studied in rabbits with dietary-induced hyperlipidemia. Two sets of New Zealand White rabbits (eight rabbits in each group) were fed either 0.25% cholesterol or 0.25% cholesterol/1% BHT for a total of 6 wk. Serum lipid levels did not differ between the two groups. 3 wk after the start of the study, a balloon injury of the aorta was performed, after which the rabbits were kept on their respective diets for another 3 wk. After this period of time, the rabbits were killed and their aortas were investigated. The BHT-treated rabbits had only one fourth of the intimal thickness (P < 0.0001) and half the number of SMC/mm intima (P < 0.001), as compared to the rabbits fed only cholesterol. There was also a lower number of macrophages in the BHT-treated group. T lymphocytes were present in the intima of cholesterol-fed rabbits, whereas no such cells could be identified in the BHT-fed animals. There were significantly lower levels of autooxidation products of cholesterol (7-oxocholesterol, cholesterol-5,6-epoxide, and 7 beta-hydroxycholesterol) in the aortas of BHT-treated rabbits, P < 0.001. In conclusion, the antioxidant BHT effectively inhibited the accumulation of intimal SMC and the development of intimal thickening of the aorta in hypercholesterolemic rabbits after a balloon catheter-induced injury. These results indicate that antioxidants may modify intimal response to injury.

Actins↗

The correlation of symptoms, occult blood tests, and neoplasms in patients referred for double-contrast barium enema.

One hundred and forty-nine patients (86 women) with a mean age of 64 years (52-74 years), referred for double-contrast barium enema (DCE), were invited to have fecal occult blood test and rectosigmoidoscopy (60 cm) (RSS) before the DCE. Carbon dioxide was used for inflation at RSS to enable the two examinations to be done at the same time. Eight adenomas < 1.0 cm in diameter, 11 adenomas > or = 1.0 cm in diameter, and 5 carcinomas were diagnosed in altogether 23 patients. There was no correlation between symptoms, diverticula, or neoplasm, but a positive rehydrated Hemoccult II test was correlated to the presence of neoplasms (cancer and adenoma > or = 1.0 cm in diameter), but Hemoccult is not suitable as selection basis for work-up of symptomatic subjects. To diagnose colorectal neoplasms, we have to accept a certain number of negative work-ups of the large bowel. If DCE is chosen for work-up of the large bowel, it has to be combined with rectosigmoidoscopy (60 cm).

Adenoma↗

Thrombin inactivation and the effects of antithrombin and heparin in a recirculating Langendorff preparation.

A recirculating Langendorff preparation was developed in order to study the effects of antithrombin III (AT) and heparin on thrombin inactivation in the capillary bed. Using this technique, rat hearts were shown to inhibit approximately 50% of the recirculated thrombin, while surface-bound thrombin displayed no enzymatic activity towards recirculated fibrinogen. By displacing thrombin bound to the endothelial surface with Polybrene, thrombin enzymatic activity was found to be equally active against a synthetic chromogenic substrate (S-2238) and fibrinogen. This indicates that thrombin bound to the capillary endothelial surface is not coagulantly active, but, when displaced from the endothelium, its coagulant activity is retained. Hearts pretreated with AT or heparin had no effect on thrombin inhibition or surface-bound thrombin, although there was an uptake of both substances to the heart. These findings are in contrast with the results obtained from large vessel preparations, where pretreatment with AT increased thrombin inhibition and also demonstrated lower levels of surface-bound thrombin, and where heparin eluted endogenous AT from the endothelium. It is concluded that AT plays a more important role in the inhibition of thrombin on large vessels than in the microcapillary system where thrombomodulin is the major inactivator of thrombin.

Animals↗

Peroperative anticoagulation with antithrombin or heparin in infrainguinal bypass surgery.

Patients suffering from atherosclerosis may have a hypercoagulable state which is further aggravated by surgery. Thrombin, a central enzyme in the coagulation process, cleaves fibrinogen to fibrin. Therefore, inhibition of thrombin is an important anticoagulant mechanism. This is accomplished by heparin in concert with antithrombin III (AT), but vessel wall glycosaminoglycans may act as substitutes for heparin and catalyse thrombin inhibition. The present study examines whether administration of AT or heparin is effective as an anticoagulant during infrainguinal bypass surgery. Preoperatively and during surgery the patients had elevated levels of fibrinogen, fibrinopeptide A (FPA) and thrombin-antithrombin (T-AT) complexes. There were higher levels of FPA in the venous outflow from the ischemic leg than in the arterial inflow. Taken together these measurements indicate ongoing coagulation in the operated leg. Administration of heparin decreased FPA levels and prevented intraoperative graft thrombosis, whereas in patients receiving AT, T-AT levels increased but FPA levels were unchanged. In the latter group, intraoperative graft thrombosis occurred in a high proportion. Based on additional case histories in these patients with hypercoagulability, it is suggested that fibrinogen is a risk factor for thromboembolic complications and that a combination of low dose of heparin and AT might be an effective regimen to prevent intraoperative thrombosis with a low risk of haemorrhage.

Adult↗

The anatomic range of examination by fibreoptic rectosigmoidoscopy (60 centimetres).

The purpose of the study was to investigate the anatomic location of the flexible rectosigmoidoscope (60 cm) when introduced as far as technically possible. One hundred and forty-nine consecutive patients referred for double-contrast enema (DCE) were examined with rectosigmoidoscopy before the radiologic examination, and CO2 was used for insufflation. A plain abdominal film was taken to locate the tip of the instrument when 60 cm or as much as possible of the instrument had been introduced. The sigmoid loop was passed and the tip of the scope located in the ascending colon or at the left flexure in 99 (66%) of the patients, and in a further 27 (18%) the upper part of the sigmoid colon was reached. The sigmoid colon had been passed in 71%, 80%, and 44% when 60, 50, and 40 cm of the instrument was introduced, respectively. DCE could be performed at the same session as the rectosigmoidoscopy, as CO2 was quickly absorbed. In the vast majority of patients the sigmoid colon can be inspected with a rectosigmoidoscope.

Adult↗

Effects of local hyperemia and edema on the biological zero in laser Doppler fluxmetry (LD).

The method of laser Doppler (LD) fluxmetry records the flux of moving blood cells and particles in a small tissue volume. However, also during complete arterial occlusion a flux-independent signal can be recorded, which is sometimes significantly different from the electrical zero of the instrument. This part of the signal has been called the biological zero (BZ), and can sometimes represent up to 80% of the total LD signal. In the present study, we investigated the influence of induced hyperemia produced by methylnicotinate and histamine respectively, both vasodilators but only histamine giving edema. Eleven legs of nine healthy subjects were studied. Test sites on the dorsal skin of the foot were prepared with a) histamine (10 mg/ml), b) methylnicotinate (0.1 mol/l) and c) saline. The substances were administered onto the skin with a lancet as the prick test procedure. The basal LD was measured before, and the BZ during an arterial occlusion obtained with a cuff at the ankle. Histamine induced a wheal and edema in all subjects, while methylnicotinate only caused erythema. Basal LD was significantly (p less than 0.01) increased by both substances compared to saline. The BZ was significantly higher (p less than 0.01) with histamine than with both saline and methylnicotinate. The results show that BZ is increased by vasodilation, and still more so by edema formation. It is concluded that the BZ value must always be recorded and taken into consideration when LD blood cell flux is measured in the skin.

Adult↗