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Biomedical subjects

B Lindblad

Publications and source records attributed to B Lindblad.

At least 145 records · Page 8Linked to original sources

Effect of anticoagulant and antiplatelet drugs on in vitro smooth muscle cell proliferation.

Effects of anticoagulant and antiplatelet drugs on vascular smooth muscle cell plating efficiency and proliferation were assessed using in vitro tissue culture techniques. Canine carotid artery smooth muscle cells were derived, pooled and plated into tissue culture cluster wells to which various drugs were added. Regular beef lung and porcine intestinal and low molecular weight porcine intestinal heparins reduced smooth muscle cell counts. Among antiplatelet drugs, reduced smooth muscle cell counts were seen with dipyridamole and ibuprofen, as well as with the combinations of ASA and dipyridamole, and ASA and dazoxiben. Although in vitro results cannot necessarily be extrapolated to in vivo settings, especially in regard to antiplatelet drugs, results of this study indicate direct effects of certain commonly used clinical agents in reducing smooth muscle cell growth.

Animals↗

Protamine reversal of anticoagulation achieved with a low molecular weight heparin. The effects on eicosanoids, clotting and complement factors.

Hemodynamic and hematologic effects of protamine reversal of low molecular weight heparin (LMWH) anticoagulation with and without protamine pretreatment, as well as reversal of anticoagulation with unfractionated standard heparin (SH), were studied in canine subjects. Protamine reversal caused less severe thrombocytopenia in the two LMWH groups compared to SH animals, while neutropenia occurred equally in all groups. Cl-esterase inhibitor levels were minimally increased, whereas C3 levels and leucotriene levels were unaltered. TxB2 and 6-keto-PGF1 alpha increased during protamine reversal of LMWH anticoagulation. TCT and APTT were affected less with LMWH than SH anticoagulation. Anti-Xa levels increased with anticoagulation in all animals, but protamine did not reverse the elevated anti-Xa levels in LMWH anticoagulated dogs to the same degree as occurred with SH anticoagulation. TCT, APTT and bleeding times were normalized by protamine in all animals. Protamine reversal of LMWH anticoagulation with or without protamine pretreatment did not reveal any clear differences in eicosanoids or complement factors compared to SH anticoagulation, although differences in anti-Xa activity clearly separated these two heparins.

Animals↗

125I-fibrinogen uptake on peripheral venous cannulas: a comparison between different cannula materials and coatings.

Using a similar technique as 125I-Fibrinogen uptake test for detection of deep venous thrombi, the radioactivity over cannulas inserted into veins on the dorsal aspect of the hands was measured 1, 2, 4 and 24 h after insertion. In three groups of 10 postoperative patients it was by random allocation inserted on one side a siliconized tetrafluorethylene cannula and on the other side one of either: a nonsiliconized tetrafluorethylene cannula and on the other side one of either: a nonsiliconized tetrafluorethylene, a heparinized tetrafluorethylene or a fluorethylenpropylene cannula. The same volume and type of infusion was given in both cannulas. No difference in protein deposition was seen between siliconized and nonsiliconized tetrafluorethylene. A tendency of lower protein deposition, especially at 24 h on heparinized tetrafluorethylene was found. The fluorethylenpropylene cannulas had both over cannula and adjacent vein higher protein deposition at all measurements compared to the siliconized tetrafluorethylene cannula (p less than 0.01). The results implicate that fluorethylenprophylene could induce a higher incidence of thrombophlebitis than tetrafluorethylene cannulas.

Adsorption↗

Alternative techniques of seeding cultured endothelial cells to ePTFE grafts of different diameters, porosities, and surfaces.

Attachment of 111Indium-oxine labeled cultured canine venous endothelial cells to expanded polytetrafluorethylene (ePTFE) grafts was evaluated in vitro. Three alternative seeding techniques were studied in grafts having different diameters, porosities, and surfaces, including: (I) manual milking of blood containing endothelial cells within the graft; (II) a two-step procedure of incubating grafts initially with blood and then with an endothelial cell suspension; and (III) mechanical spinning of grafts filled with blood containing endothelium. Method II had significantly higher cell attachment to the graft (11.6%) than did Method I (1.5%) or III (4.7%). A somewhat higher seeding efficiency was noted in 10-mm-I.D. grafts (11.6%) compared to 6-mm-I.D. grafts (6.3%). Different graft porosity, created by altering internodal distances, did not cause significant changes in cell attachment (10 microns, 13.4%; 30 microns, 6.3%; 90 microns, 16.0%). Fibronectin-coated surfaces, which should have enhanced cell adhesion, demonstrated a 6.0% cell attachment, a lower efficiency than the 11.6% observed with a blood coating alone. Acetone-soaked surfaces, which should have predictably exhibited less hydrophobicity, produced quite variable attachments (range 3.4 to 59.7%, mean 23.4%). In the present investigation the best seeding technique was method II, the two-step incubation procedure. Consistent differences were not noted with various ePTFE graft configurations or surfaces.

Animals↗

Haemodynamic and haematologic alterations with protamine reversal of anticoagulation: comparison of standard heparin and a low molecular weight heparin fragment.

Reversal of anticoagulation with protamine sulfate causes many adverse haemodynamic and haematologic effects which could be due to differences in the mechanism of action of standard and low molecular weight heparin. Three groups of dogs were investigated: one group received normal saline pretreatment followed by heparinisation with standard heparin 150 IU/kg followed by protamine sulfate reversal 1.5 mg/kg after aortic interposition grafting: the second group were given normal saline pretreatment followed by heparinisation with low molecular weight heparin 150 U antiXa/kg and after grafting protamine sulfate reversal 1.5 mg/kg. The third group were given protamine sulfate pretreatment 2.25 mg/kg followed by low molecular weight heparin 150 U antiXa/kg and later protamine sulfate reversal 1.5 mg/kg after grafting. The same haemodynamic changes were seen regardless of the type of heparin or pretreatment with protamine given along with low molecular weight heparin. There was a suggestion that regular heparin cause a more pronounced increase in pulmonary artery pressure and a decrease in heart rate. On the other hand the systemic hypotension and reduction of cardiac output seemed more pronounced in the low molecular weight heparin group. Platelet count decreased less in the low molecular weight heparin group, but white blood cell count was equally reduced. Pretreatment with protamine did not abolish the adverse effects of protamine when reversing anticoagulation achieved with low molecular weight heparin, a finding not shared with standard heparin-protamine interactions.

Animals↗

Effect of different oxygen saturations on venous versus arterial endothelial cell growth in vitro.

Canine carotid arterial and external jugular venous endothelial cells were derived, cutured, passed, and pooled. Three X 10(6) cells were seeded into capped roller-bottles. Three roller-bottes were seeded with venous, and another three with arterial derived endothelial cells for each of three "oxygen saturations" 5, 20 and 50% O2 respectively, and incubated for seven days and then counted. Arterial endothelial cells showed no cell proliferation in high oxygen saturation compared to an 83% increase in cell numbers when oxygen supply had been held to 20%. Venous endothelial cells showed no cell proliferation in medium or high oxygen supply but low oxygen supply (5% O2) gave a 91% increase in cell counts. The small number of roller-bottles investigated does not allow firm conclusions but our results warrant further evaluation.

Aerobiosis↗

Pulmonary vascular response to live Escherichia coli: influences of different antiplatelet substances.

The aim of this study was to investigate whether pretreatment with drugs that interfere with platelet functions in different ways could modify the pulmonary vascular response in a porcine septic shock model. Septic shock was induced by i.v. infusion of live Escherichia coli bacteria. Bacteriemic animals were divided into five groups: untreated or pretreated with a thromboxane-A2 synthetase inhibitor (UK 38 485), a serotonin-receptor antagonist (ketanserin), a combination of these two drugs, or a platelet antiaggregating drug (dipyridamole). E. coli induced significant pulmonary hemodynamic and respiratory changes. The pulmonary responses to E. coli infusion were attenuated after pretreatment with UK 38 485 but unaffected by prior administration of ketanserin or dipyridamole. The combined pretreatment did not attenuate the pulmonary hypertension or other pulmonary responses to E. coli more than UK 38 485 alone. Dipyridamole did not alter the pulmonary circulation after bacterial infusion. It was concluded that thromboxane-A2 is an important, but not the only, mediator of the pulmonary vascular response in septic-shocked pigs and that factors such as serotonin and platelet aggregability seem to be of minor, if any, importance for the hemodynamic response.

Animals↗

The rationale for "second-look operation" in mesenteric vessel occlusion with uncertain intestinal viability at primary surgery.

In a 10-year period, 80 patients, median age 78 years, were operated on for mesenteric vascular occlusion--arterial in 50 cases, venous in 24 and of uncertain etiology in six cases. Abdominal pain out of proportion to physical findings occurred in only eight cases. Vague abdominal symptoms with increasing tenderness led to surgical exploration in most cases. Median patient delay was 34 hours and doctor's delay 15 hours. Resection was primarily nonfeasible in 28 cases. Primary resection without second-look operation was performed in 32 cases, in seven of which signs of anastomotic insufficiency appeared. In the remaining 20 cases, primary resection (18) and/or embolectomy (3/2) was followed by a planned second-look operation within 24 hours, when five resections were performed. In a patient with viable anastomosis at second look, there were late signs of anastomotic insufficiency. Although the data do not permit firm recommendations, use of second-look operation in patients with doubtful viability of the intestine may reduce the extent of resection at primary exploration and also the incidence of insufficient anastomosis.

Adult↗

The influence of ketanserin on hemostasis in vitro.

Ketanserin is a new selective 5-HT2 receptor blocker. It has been used to indirectly study the influence of serotonin on hemostatic function in vitro. Coagulation and fibrinolysis in vitro were not affected. In high doses adrenalin induced platelet aggregation was inhibited but no influence was seen on collagen or ADP induced aggregation. It can be concluded that it is not very likely that serotonin plays an important role in initial hemostasis. However, the findings ought to be confirmed in vivo.

Adenosine Diphosphate↗

Low molecular weight heparin once daily compared with conventional low-dose heparin twice daily. A prospective double-blind multicentre trial on prevention of postoperative thrombosis.

In a randomized, prospective, double-blind multicentre trial, the effect of conventional low-dose heparin 5000 units twice daily, was compared with that of a low molecular weight heparin fragment (4000-5000) 5000 anti-factor Xa units once daily. Four hundred and thirty-two patients fulfilled the inclusion criteria and were analysed for development of deep vein thrombosis (125I-labelled fibrinogen test) and haemorrhagic complications. Thrombosis occurred in a 4.3 per cent of patients in the low-dose heparin group and in 6.4 per cent of patients in the heparin fragment group, a difference which is not significant. There was a significant delay in the onset of thrombosis in the heparin fragment group. Mortality did not differ between the groups, nor did peroperative blood loss or transfusion requirements or infectious complications. Haemorrhagic complications occurred significantly more often in the fragment group (11.6 per cent) than in the conventional heparin group (4.6 per cent). Patients in the heparin fragment group experienced local pain following the subcutaneous injection significantly less often.

Adult↗

Nuclide imaging of vascular graft-platelet interactions: comparison of indium excess and technetium subtraction techniques.

Indium-111-labeled platelet adherence to ePTFE thoracoabdominal vascular prostheses in a canine model (n = 10) was quantitated by (1) an indium-111 excess technique, contrasting graft radioactivity to that in a reference region, and (2) a technetium-99m subtraction technique, with radioactivity of circulating platelets eliminated by discounting background blood activity. Variation in graft thrombogenicity was provided by seeding six prostheses with enzymatically derived autologous endothelial cells, and implanting four prostheses without seeding. Grafts were imaged at 1, 4, and 6 weeks postimplantation, with platelet labeling using indium-111-oxine and red blood cell labeling using technetium-99m. At 7 weeks grafts were excised and gamma activity was measured in proximal, middle, and distal segments. Luminal generation of TxB2 and 6-keto-PGF1 alpha from midportions of grafts was assayed. Indium-111 excess ratios at 6 weeks correlated with actual gamma activity of excised grafts (proximal r = 0.80, P less than 0.01; middle r = 0.73, P less than 0.05; distal r = 0.48, ns) but such a correlation did not exist for the technetium-99m subtraction technique (r = -0.05, -0.25, and 0.16, in the three segments, respectively, all ns). The ratio of graft to aortic TxB2 production revealed a positive correlation with graft gamma activity (r = 0.87, P less than 0.01), and the ratio of graft 6-keto-PGF1 alpha to TxB2 production also correlated with gamma counts (r = -0.64, P = 0.05). In this experimental setting technetium-99m subtraction analysis was an imprecise method of detecting graft platelet accumulation, whereas indium-111 excess ratios proved to be a more accurate method of quantitating vascular prosthetic thrombogenicity.

Animals↗

Protamine pretreatment attenuation of hemodynamic and hematologic effects of heparin-protamine interaction. A prospective randomized study in human beings undergoing aortic reconstructive surgery.

Hemodynamic and hematologic responses to protamine sulfate reversal of heparin's anticoagulant effects were studied in 15 consecutive randomized patients undergoing aortic reconstructive surgery. In a double-blinded manner, patients were pretreated with either normal saline solution (n = 8) or protamine (0.75 mg/kg/3 min, n = 7) 5 minutes before heparinization (150 IU/kg). After aortic grafts were placed, protamine (1.5 mg/kg/3 min) was administered intravenously to reverse the heparin. Arterial blood pressure, heart rate, pulmonary artery and capillary wedge pressure, central venous pressure, and cardiac output were monitored, as were platelet count, white blood cell count, activated clotting time, total hemolytic complement levels, and C3a levels. Calculated parameters included systemic vascular resistance and pulmonary vascular resistance. Pretreatment with protamine compared with saline solution prevented the hypotension (+6 vs. -16 mm Hg, p less than 0.05) and declining pulmonary artery pressure (+1 vs. -7 mm Hg, p less than 0.01) observed with protamine reversal of heparin. Significant differences between the two groups in central venous pressure and pulmonary vascular resistance were of less clinical relevance. Protamine pretreatment lessened the thrombocytopenia found during reversal compared with saline-pretreated patients although the difference was not statistically significant. Minimal hypotension occurring after protamine pretreatment alone was not accompanied by hemodynamic or hematologic changes, other than decreased heart rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Does dihydroergotamine reduce plasma volume?

Indications on a plasma volume reduction by dihydroergotamine (DHE) has been found in earlier studies. This study was made in order to further evaluate such a change. In animal experiments (sheep, n = 10) measurements were performed of red blood cell volume and plasma volume using radioactive labelling techniques. Red blood cell volume was unchanged but a plasma volume decrease of 10% was found after two hours and it persisted for 24 hours. In postoperative patients (n = 9), who had been given an infusion of ringer-glucose (5.5%) at a rate of 100 ml/hour, DHE caused an increase in diuresis but neither ADH (n = 9) nor aldosterone (n = 3) levels were changed. The data from the present study further support the earlier findings of a reduced plasma volume after DHE administration. The main effect of dihydroergotamine is on the vascular bed and especially on capacitance vessels (increased tonus). The reduced plasma volume by DHE seems to be one additional effect of DHE.

Aldosterone↗

Prospective double-blind comparison between Fragmin and conventional low-dose heparin: thromboprophylactic effect and bleeding complications.

In a randomized, prospective, double-blind multicenter trial, the effect of low-dose conventional heparin (5,000 IU/12 h) was compared to a low molecular weight (LMW) heparin fragment (5,000 antifactor Xa U/24 h). 432 patients 40 years or older undergoing elective abdominal surgery were included, 382 correctly treated. 45% had malignant diseases. The groups did not differ in risk factors. Analysis was made both on the basis of intention to treat and correct prophylaxis. No difference in results between these 2 groups was seen. Deep vein thrombosis (125I-fibrinogen) occurred in 4.3% of the low-dose heparin group and in 6.4 of the LMW heparin group. There was a significant delay in the onset of deep vein thrombosis in the LMW heparin group. Mortality, peroperative blood loss, transfusions or infectious complications did not differ. Hemorrhagic complications occurred significantly more often in the LMW heparin group (11.6%) than in the low-dose heparin group (4.6%). Significantly fewer patients experienced local injection pain in the LMW heparin group. APTT and AT III were similar in both groups, but anti-Xa activity was significantly higher in the LMW heparin group. Single daily LMW heparin injection reduced the frequency of deep vein thrombosis to the same level as low-dose heparin twice daily. The dose or administration interval of LMW heparin in this study caused significantly more bleeding complications.

Aged↗

Endothelial cell seeding efficiency onto expanded polytetrafluorethylene grafts with different coatings.

Initial adherence of 111Indium-oxine labeled, cultured canine venous endothelial cells to expanded polytetrafluorethylene (ePTFE) grafts was evaluated using different precoatings of the surface or different pretreated cells. The precoatings evaluated consisted of blood for 5 (Group I) or 15 min (Group II), fibronectin (Group IV), and cryoprecipitate (Group VI). In addition to endothelial cells subcultured immediately before labeling, cells subcultured 48 hours prior to labeling and kept in suspension were studied. Such cells were evaluated on grafts precoated with blood for 5 min (Group III) and fibronectin precoated surfaces (Group V). The amount of fibronectin that adhered to the graft surface with our technique was less den 1%. Seeding efficiency was higher with the blood precoated surfaces (5.3, 3.0, 2.2% in Groups I, II and III respectively) than fibronectin (1.7%, 1.7% in Groups IV, V respectively) or cryoprecipitate (1.9%, Group VI) precoated surfaces. No significant difference between cells immediately subcultured and these kept in suspension for 48 hours regarding adherence to blood (5.3 vs. 2.2%) or fibronectin precoated (1.7 vs. 1.7%) grafts was documented. The seeding efficiency of ePTFE grafts is low and further efforts to improve adherence must be made. From the present studies we recommend the use of blood precoating for about 5 min followed by cell incubation for approximately 10 min in order to achieve optimal seeding efficiency.

Animals↗