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Biomedical subjects

J Swedenborg

Publications and source records attributed to J Swedenborg.

At least 73 records · Page 4Linked to original sources

Heparin cofactor II significance for the inhibition of thrombin at the injured vessel wall.

The thrombin inhibitory role of antithrombin III (ATIII) and heparin cofactor II (HCII) was studied in vitro using intact and injured rabbit aortae. When intact vessels were loaded with thrombin and then exposed to either heat defibrinogenated human plasma (HDHP) or ATIII the same degree of thrombin inhibition was achieved demonstrating that ATIII was the only plasma component involved in thrombin inhibition on the intact vessel wall. When the media of the vessel wall was loaded with thrombin and then exposed to ATIII or HCII a significantly higher thrombin activity remained on the surface than when it was exposed to defibrinogenated plasma. A mixture of ATIII and HCII resulted in a greater inhibition of thrombin than ATIII or HCII alone. It is concluded that, contrary to what happens on the endothelium, HCII and ATIII inhibit additively thrombin on the injured vessel wall. HCII thus plays an essential role for the inhibition of thrombin at the injured vessel wall. It is also concluded that an additional plasma component participates in thrombin inhibition on the media but its contribution is negligible as compared with ATIII or HCII.

Animals↗

Thrombin-inhibitory capacity of the injured vessel wall.

The present study examined the appearance of thrombin activity in vitro after single and repeated in vivo balloon injury of the rabbit aorta. The in vitro ability of the injured vessel wall to bind and subsequently inhibit thrombin in the presence of defibrinogenated plasma was also assessed. Thrombin activity was assayed by measuring the levels of fibrinopeptide A generated in the presence of fibrinogen. These findings were correlated with the changes observed in light and electron microscopy. Thrombin activity on the vessel wall was increased five minutes and three hours after the initial and the repeated injury, and returned to control values one week after the initial injury. When the inhibition of thrombin was assayed in the presence of defibrinogenated plasma, a diminished inhibition capacity was observed after the repeated injury, which correlated with deposition of fibrin and an enhanced inflammatory reaction as measured by the density of granulocytes covering the injured neointima. Decreased thrombin inhibitory capacity of the injured neointima appears to be linked with its increased thrombogenicity.

Angioplasty, Balloon↗

Changes in middle cerebral artery flow velocity and pulsatility index after carotid endarterectomy.

Transcranial Doppler sonography (TCD) was used in 33 patients undergoing carotid endarterectomy (CEA). Mean flow velocity (MCA MV) and the pulsatility index in the middle cerebral artery (MCA PI) were measured pre- and on six occasions postoperatively. The MCA MV was reduced by anaesthesia but was increased postoperatively (+43%, p less than 0.001) compared to the preoperative value and was still increased at late follow-up after several months. The MCA PI, which was lower preoperatively than normally reported in this age group, was not changed by anaesthesia but then rose and remained elevated, i.e. within normal limits 72 h postoperatively (+30%, p less than 0.01) as well as at late follow-up. No significant changes in MCA MV or MCA PI were noted on the contralateral side. The results from this study support earlier findings from invasive studies showing that CEA results in an increased flow in the middle cerebral artery on the operated side and an increased MCA PI suggests an increased resistance on the operated side. The findings are compatible with an increased cerebral blood flow during the first days after CEA and with the operated side supplying a greater part of the cerebral blood flow even several months after surgery.

Aged↗

Survival in patients with abdominal aortic aneurysms. Comparison between operative and nonoperative management.

This study evaluates the risk benefit relationship in the surgical treatment of abdominal aortic aneurysm (AAA). Two hundred and thirteen patients with AAA diagnosed by CT were selectively managed depending upon the size of the aneurysm, and were followed with a mean follow-up time of 5 years and 4 months. Aneurysms greater than 5 cm were generally operated on if no serious contraindication existed. Aneurysms less than 5 cm were followed by repeated examinations and operated on if an increase in size occurred. Some small aneurysms were operated on for other reasons. Elective surgical management of 134 patients resulted in a thirty day mortality of 7.5%. Later, seven additional patients died from causes related to the surgery. Survival of electively operated patients by life table analysis was 68% at 5 years. A significantly higher mortality was noted among those who had evidence of coronary heart disease at the time of operation. Forty-two patients with AAA less than 5 cm at the initial examination were not operated on and three ruptured, but all had grown to a size greater than 5 cm at the time of rupture. Patients with AAA less than 5 cm that were not operated on had a slightly but not significantly higher mortality than those who were operated on electively. This difference was mainly attributable to deaths from cardiac causes and not to ruptures. Patients with aneurysms greater than 5 cm who were not operated on had a significantly higher mortality than those that were, only 14% in the former group survived.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Coagulant and noncoagulant thrombin enzymatic activity on the endothelium.

The present study examines the role of antithrombin III (ATIII) and heparin in the inactivation of thrombin on rabbit aortae in vitro. Thrombin on the endothelium was functionally assayed with a synthetic chromogenic substrate (thrombins) or with fibrinogen (thrombinf), measured as the liberation of fibrinopeptide A. After incubation with thrombin, residual amounts were found on the endothelium. Surface-bound thrombinf constituted approximately one-half of surface-bound thrombins. Displacement of thrombin activity from the thrombin loaded endothelial surface was achieved with Polybrene. The thrombin could be quantitatively recovered in the Polybrene solution and equal amounts of thrombins and thrombinf were found. Incubation of endothelial segments with ATIII resulted in only a minimal uptake of ATIII on the surface but in a significantly increased capacity to inactivate thrombin, whereas incubation of the segments with heparin alone had the opposite effect. The effect of ATIII could be inhibited by prior incubation with Polybrene or by a subsequent incubation with heparin. It is concluded that the vessel wall content of ATIII is one determinant for the capacity to inhibit thrombin and that ATIII is bound to glycosaminoglycans on the vessel wall since it could be displaced by heparin.

Animals↗

The influence of reactive hyperemia and leg dependency on skin microcirculation in patients with peripheral arterial occlusive disease (PAOD), with and without diabetes.

The increase in venous pressure during leg dependency causes a vasoconstriction of the distal vascular bed in healthy subjects, which is due to the so-called veno-arteriolar reflex. The aim of the present study was to investigate if this reflex is disturbed in patients with severe peripheral arterial occlusive disease (PAOD), with and without diabetes. The total skin microcirculation during rest and postocclusive reactive hyperemia (PRH) after a three minute arterial occlusion at the ankle was studied by laser Doppler (LD) fluxmetry. The LD probe was attached to the dorsal region of the foot in 10 legs of healthy control subjects, patients with PAOD, and patients with PAOD and diabetes respectively. No vasoconstriction was seen in the PAOD group when the leg was moved from the supine to the dependent position. The PRH response was also significantly (p less than 0.05-0.01) impaired compared to the controls in both positions. The diabetic PAOD patients had an almost normal reactivity in spite of an equally reduced arterial circulation as the non-diabetic patients. The results show that patients with PAOD have a significantly disturbed reactivity of the skin microcirculation in the ischemic foot, while the reactivity in diabetic PAOD patients is almost normal.

Aged↗

Atherosclerotic occlusive disease after radiation for pelvic malignancies.

We have studied 15 women who were previously treated by irradiation for pelvic malignancies and who all developed symptoms of arterial occlusive disease of the iliac arteries and the distal aorta. Risk factors were evaluated in a case control study in which each patient was compared with three individually matched controls who were treated during the same period for the same type of cancer and who did not develop arterial occlusions. We conclude that smoking habits as well as treatment by irradiation are strong predictors of the development of atherosclerotic occlusive disease. Side effects of irradiation occur in the arteries more often in patients who have also radiation reactions in other organs--for example, the bowel and bladder. Irradiation acts in combination with other atherogenic factors and this should be kept in mind when radiation treatment is planned for patients with a high risk of developing atherosclerosis.

Adult↗

Surgery in patients with von Willebrand's disease.

The risk of bleeding complications in the surgical treatment of patients with von Willebrand's disease has been evaluated. Sixty-four major surgical procedures were performed in 51 patients with various forms of von Willebrand's disease. In 18 cases, the bleeding disorder was unknown at the time of surgery, resulting in bleeding complications in 12 cases (67 per cent). Forty-five operations were carried out in patients in whom the diagnosis of von Willebrand's disease was known at the time of surgery. In these patients, the following haemostatic preparations were given: factor concentrate, fresh plasma, tranexamic acid and desmopressin. Haemostatic complications occurred in three of these operations (6.7 per cent); all were managed easily. No mortality was observed. It is concluded that patients with von Willebrand's disease do not carry an increased operative risk if appropriate precautions are taken.

Adolescent↗

Implantable catheter system for long-term intravenous chemotherapy.

Fifty-three implantable catheter systems (Port-A-Cath) were placed subcutaneously in 48 patients with malignant tumours. This device consists of a stainless steel chamber covered by a silicone membrane connected to a silicone catheter placed in a central vein. All systems were used for administration of chemotherapy. The mean function time was 187 days (range 0-867). Complications necessitating reoperation occurred in six patients. In three cases, the catheter occluded from thromboses. In two patients, wound dehiscence occurred, and in one a wound infection developed. In one case, the catheter was disconnected from the port. Four patients who had had the port removed later received new ports. One patient had the second port removed and was given a third catheter system. It is concluded that subcutaneously implantable injection ports constitute a safe and convenient access for long-term intravenous chemotherapy. The complication rate is low, and it should be possible to avoid most recorded complications in the future.

Adolescent↗

Effect of acetyl salicylic acid on increased production of thromboxane after aortic graft surgery.

Contact between blood and foreign surfaces, e.g. vascular grafts, causes activation and release of platelets. One consequence of platelet activation is production of thromboxane A2 (TxA2). The physiological effects of TxA2, i.e. platelet aggregation and vaso-constriction are counteracted by another prostanoid, prostacyclin (PGI2). Acetylsalicylic acid (ASA) causes a longlasting inhibition of platelet TxA2 production and a more shortlasting inhibition of PGI2 production. The present study examines TxA2 and PGI2 synthesis in patients receiving synthetic arterial grafts, some of which were treated with ASA. The prostanoid synthesis was evaluated by measurement of their main urinary metabolites with gas chromatography-mass spectrometry. Platelet release was evaluated by measurements of beta-thromboglobulin (beta-TG) and the plasma coagulation by measurements of fibrinopeptide A (FPA). These compounds were also measured in urine in order to avoid artifacts caused by activation of platelets and plasma coagulation during blood sampling. Following replacement of the abdominal aorta with a synthetic vascular graft there was a marked increase in the synthesis of TxA2 and PGI2. Increased levels of beta-TG and FPA were also demonstrated. Administration of ASA on the first and second postoperative days significantly reduced the synthesis of TxA2 but caused no significant effects on the other parameters measured. It is concluded that ASA may be beneficial in the postoperative period since it counteracts TxA2 with vasoconstricting and platelet aggregating properties but leaves PGI2 with vasodilating and antiaggregating properties relatively uneffected.

Aged↗

Inhibition of thrombin on subendothelium. Studies on rabbit aorta, ex vivo.

The endothelium plays an active role in inhibiting and promoting the activation of coagulation. Loss of the endothelial lining results in a thrombogenic state. The inactivation of thrombin on rabbit aorta after a superficial and deep injury to the vessel wall was studied. The thrombin enzymatic activity on the subendothelium could be modulated and decreased activity was found on both types of injured vessel segments when exposed to antithrombin III (AT). An increased activity by exposing the superficially injured vessels. Most probably, heparin elutes AT from the surface of the superficially injured vessels, but on the deeply injured surface no AT is present and, consequently, heparin has no effect in this respect. These results speak in favour of treatment with AT instead of heparin in cases of arterial injury.

Animals↗