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ABSTRACT: The effect of the fibrinolysis inhibitor tranexamic acid on early thrombus formation following microvascular trauma was investigated in the central arteries of ears in 86 rabbits (in all 172 vessels), divided into four separate blind randomised studies. In the first part a common end-to-end anastomosis was done and in the last three studies a severe trauma-arteriotomy/intimectomy was performed. Parameters studied were vessel bleeding times, patency rates, weights of intraluminal thrombotic material, haematocrit and plasma fibrinolytic activity. In the first study consisting of 14 control animals and 18 animals treated with 14 mg/kg bw of tranexamic acid, end-to-end anastomosis was performed on the central artery of one ear and on the central vein of the other ear. In the second, third, and fourth studies consisting of 18, 20, and 16 control vessels and the same number of corresponding vessels in treated animals a 7-mm longitudinal arteriotomy followed by a deep 5-mm-long intimectomy was performed. The second and third treated groups were given 14 mg/kg bw of tranexamic acid 5 min and 1 h, respectively, before reflow and the fourth group 28 mg/kg bw 5 min before reflow. The difference between the second and third studies was the addition, to mimic clinical situations, of 8.5 ml saline/kg bw 2 h before reflow in the third study. In conclusion, treatment with a single clinical dose, 14 mg/kg of tranexamic acid, did not influence vessel bleeding times or thrombus formation in the anastomotic or severe trauma models and seems safe to use. Not even a double clinical dose, 28 mg/kg, influenced thrombus formation in a statistically significant way.
Microsurgery 02/1996; 17(5):278-85. · 1.61 Impact Factor
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ABSTRACT: The study was composed of two parts, arterial and venous; the 24 rabbits in each arm were divided into three equal groups and treated with either saline (control) or 1 mg/kg body weight (bw) of a new recombinant hirudin HBW 023 given as a single dose or standard heparin 1 mg/kg bw followed by quarter doses of heparin every half hour. Both arms included a control group given equal volumes of saline. The study continued for 2 hours. The following parameters were evaluated: bleeding times from arteriotomy/venotomy, patency rates, and the weights of thrombotic materials. Plasma samples were taken for evaluation of anti-factor lla (anti-Flla), anti-factor Xa (anti-Fxa), and activated partial thromboplastin time (APTT). The bleeding times were significantly prolonged but were still within clinically acceptable levels, following both HBW 023 and heparin treatment. Patency rates were significantly improved in both the arterial and venous arms following HBW 023 and heparin treatment. A corresponding reduction in thrombotic materials was simultaneously registered in the arterial and venous arms following HBW 023 and heparin treatment. Hirudin (HBW 023) significantly improved the reduction compared with the heparin group in the venous study. Heparin treatment caused expected high levels of anti-FXa and prolonged APTT, but hirudin, being at least as effective in antithrombotic potency, changed the pre-treatment levels only slightly. Anti-Flla levels were immediately increased by both heparin and hirudin (the highest levels) but reached low levels after 2 hours of single-dose hirudin treatment, despite a simultaneously excellent antithrombotic effect. We conclude that the new recombinant hirudin HBW 023, like standard heparin, is a highly efficient antithrombotic agent in both small arteries and veins following severe vessel wall trauma. The bleeding times were simultaneously prolonged significantly (still within acceptable limits) following both heparin and HBW 023 treatment in the arterial arm but were only prolonged following heparin treatment in the venous arm. The advantage of r-hirudin HBW 023 was furthermore the single dose administration.
Microsurgery 02/1996; 17(2):89-96. · 1.61 Impact Factor
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ABSTRACT: 5-Fluorouracil (5-FU) is a widely used antineoplastic agent. 5-FU induced cardiotoxicity is a still relatively unknown side-effect of this drug. This phenomenon could be due to a direct cytotoxic effect on the endothelial cells. We tested this hypothesis in an experimental study in rabbits, by scanning or transmission electron microscopic evaluation of endothelium in small arteries (the central artery of the ear) after in vivo treatment with 5-FU. Both local and systemic effects of 5-FU on endothelium were studied 15, 30, 60 and 120 minutes after intra-arterial or intraperitoneal treatment. Perfusion fixation at physiological pressure and temperature was used in order to minimize damage to the endothelium during the preparation procedure. Eighteen rabbits weighing 2.5-3.0 kg were used, and 6 animals served as controls. The following parameters were evaluated: vessel wall and endothelial cell contraction, cell edema, cytolysis, occurrence of denuded areas, platelet adhesion/aggregation and fibrin formation. For the description of each parameter a scale of negative points was used. Irreversible cell damage was observed in 5-FU treated animals: disruption of the endothelial sheet and patchy exposure of the subendothelium, sometimes as a focus for thrombus formation. Our findings support the hypothesis that the thrombogenic effect of 5-FU secondary to its direct cytotoxic effect on endothelium might be one of the pathophysiological mechanisms behind 5-FU induced cardiotoxicity.
Scanning microscopy 07/1995; 9(2):561-76.
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ABSTRACT: A clinical dose of dextran 70 had significant antithrombotic effects in small, severely traumatized veins, and the effect was enhanced by the addition of low-molecular-weight heparin. These effects were achieved without bleeding problems in this model.
Plastic & Reconstructive Surgery 09/1994; 94(2):352-8. · 3.38 Impact Factor
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ABSTRACT: A severe microarterial trauma (arteriotomy/intimectomy) was introduced to the central arteries of rabbit ears. Twenty-one patent vessels, 3 at each interval of 2 hours, 1, 3, 7, 14, 30, and 90 days after reperfusion were taken for light and scanning electron microscopy studies. These vessels remained patent at all time intervals. A physiological "in vivo" perfusion technique with fixation fluid of normal temperature (37 degrees C), pressure (120 mm Hg) and osmolarity (300 mOsm) was used to ensure fixed relaxed vessels. The endothelial, internal elastic, and part of the medial layers of vessel walls were removed following intimectomy. The inner surface of the intimectomy region was irregular and partly covered with thrombotic materials between 2 hours and 3 days postreperfusion. Endothelialization of the traumatized region was first observed at 3 days and was completed between 7 and 14 days. Intimal hyperplasia developed during this period and had not diminished in thickness by 30 or 90 days. The trauma and healing process of the arteriotomy/intimectomy are similar to the healing of vascular anastomoses and virtually identical to the clinical trauma of vessel avulsion, but neointima formation is more pronounced and engages vessel walls far outside the intimectomy site.
Microsurgery 02/1994; 15(2):130-40. · 1.61 Impact Factor
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ABSTRACT: Twenty-seven rabbits divided into 4 groups (2 control groups) received saline, standard heparin (400 IU both as anti-F Xa and activated partial thromboplastin time per kg of body weight), or low molecular weight heparin (lmwh) (Fragmin 560 IU as anti-F Xa and 140 IU as APTT units per kg of body weight). The figures represent the total dose given over 3 hours. The central arteries of the rabbits' ears were prepared and positioned in clamps. Platelets labeled with 32P were injected. Arteriotomy/intimectomy was performed. After reestablishment of blood flow, arteriotomy bleeding times, platelet accumulation, patency, and weight of thrombotic materials were measured. The bleeding time in the Heparin Group was significantly prolonged compared with its control group. But the bleeding times between the LMWH Group and the control group were not significantly different. The patency rates were increased in both the Heparin Group (100%, p < 0.01) and the LMWH Group (73%, p = 0.078) compared with respective control groups (43-50%). The mean weights of thrombotic material in each artery were significantly lower in the Heparin Group and in the LMWH Group than in their control groups. The mean values of radioactivity in all groups increased up to 15 minutes after the vessels were reperfused. There were no statistical differences between the treated groups and control groups. It was concluded that standard heparin is a very powerful inhibitor of thrombosis during the most crucial hours after reperfusion of severely traumatized small arteries, without significant effects on primary platelet adhesion/aggregation.(ABSTRACT TRUNCATED AT 250 WORDS)
Annals of Plastic Surgery 10/1993; 31(3):255-61. · 1.32 Impact Factor
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ABSTRACT: In two separate blind, randomized studies, 48 rabbits were divided into five groups. Three treated groups received dextran 70 (0.51 g/kg) as a single injection, dextran 70 combined with low molecular-weight heparin (LMWH) (560 IU/kg as anti-FXa and 140 IU/kg as APTT in 3 hr), and dextran 70 plus tranexamic acid (14 mg/kg) following severe arterial trauma (arteriotomy/intimectomy). Two control groups received the same amount of saline. The bleeding times from the arteriotomy were recorded, and patency rates and the weight of thrombotic materials were registered 2 hr after reperfusion of the trauma region. The bleeding times in three treated groups, all including dextran, were significantly prolonged compared to the control groups (P < 0.05 or 0.01). The patency rates of treated groups, which were 100% (18/18 vessels patent) in the dextran-treated group, 90% (18/20 vessels patent) in the dextran+LMWH group and 95% 19/20 vessels patent) in dextran+tranexamic acid group, were significantly higher than those of their control groups (55-67% patent vessels) (p < 0.05 or 0.01). The mean weights of thrombotic materials were significantly reduced in the treated groups compared to the corresponding control groups (p < 0.01). In conclusion, dextran 70 in an ordinary dose exerted such a profound antithrombotic effect (100% patency) in small traumatized arteries that the addition of a high dose of LMWH could not further improve patency rates or decrease thrombotic materials but did not prolong vessel bleeding times compared to the single dextran treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
Microsurgery 01/1993; 14(4):289-95. · 1.61 Impact Factor
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ABSTRACT: Administration of low-molecular-weight heparin (LMWH) and standard heparin was studied by evaluating vessel bleeding, patency, and thrombotic material following severe vascular trauma. Arteriotomy and intimectomy or venotomy and intimectomy were performed on small rabbit arteries or veins in two separate blinded studies. All vessels were closed using a continuous microvascular suture. Patency and weight of thrombotic materials were evaluated 2 hr after reperfusion. In the arterial study, two groups of 23-24 arteries were treated with saline or LMWH systemically. Bleeding times were 89 +/- 15 sec in the control group and 103 +/- 27 sec in the LMWH group; there was no significant difference between the groups. Patency was significantly increased in the LMWH group (79%) compared to the control group (52%). The weight of thrombotic material in the LMWH group (1.39 +/- 0.20 mg per artery) was significantly different compared to the control group (2.19 +/- 0.22 mg per artery). In the venous study, 65 veins were divided into three groups (21-23 vessels/group) and treated with systemic saline, heparin, or LMWH. Bleeding times in the conventional heparin group (37 +/- 7 sec), the control group (23 +/- 3 sec), and LMWH group (22 +/- 4 sec) were not significantly different. The patency rates were significantly increased in the heparin (42%) and LMWH (39%) groups compared to the control group (0%). The weight of thrombotic material in each vein was significantly less in the LMWH (1.07 +/- 0.24 mg) and heparin (1.78 +/- 0.52 mg) groups than in the control group (3.78 +/- 0.29 mg).(ABSTRACT TRUNCATED AT 250 WORDS)
Microsurgery 02/1992; 13(6):295-8. · 1.61 Impact Factor
