Contributions
Abstract: PB2226
Type: Publication Only
Background
Rethrombosis and thromboembolia are the most common side effects of thrombolytic therapy. One of the possible causes of thrombosis is the entering of thromboplastin in the blood stream. Marker of thromboplastin is an intrinsic membrane glycoprotein 5’-nucleotidase (5’NT) that is present as an enzyme in a wide variety of cells. Recently it was shown that compensatory reaction of haemostasis system by using different fibrinolytic drugs was connected with the stimulation of the sympathetic nervous system. Besides, it is known that selective and nonselective α–adrenoreceptor blocking agents have fibrinolytic and antiplatelet effects. The prevention of thrombosis complication is very important field of pathophysiology and medical practices. Therefore, we studied effects of different α–adrenoreceptor antagonists and the influence of these substances combinations with various anticoagulant and fibrinolytic agents on blood coagulation during many years.
Aims
The study of the influence of low molecular weight heparin (LMWH, 4.4 kD) and high molecular weight heparin (HMWH) and their combinations with different α –adrenoreceptor antagonists (AA) on experimental thrombosis prevention.
Methods
Experiments were carry out on 50 white laboratory rats weighing 200-230 g according to the ethical principles of the Helsinki Declaration. Anticoagulant and antithrombotic effects of LMWH or HMWH were studied in two rat models of thrombosis – thrombosis in v. jugularis (Wessler) and thrombosis in arterio-venous shunt (direct registration of blood pressure). The α–AA digydroergotoxin (DET – 1mg/kg), α1–AA prazosin (PZ – 2mg/kg), LMWH or HMWH (40 USP/kg) were injected in v.jugularis. Saline was administrated in control rat groups. The thrombus were formed 15 or 180 min after substances injected. The degree of thrombus formation (TF) was detected in ball (Wessler model) and by time of TF (arterio-venous shunt model). In blood plasma the activity of 5’NT was detected. The results were processed statistically.
Results
The increase of anticoagulant and antithrombotic effects of LMWH or HMWH by pretreatment of DET or PZ were shown in both animal models of venous thrombosis. The degree of TF by Wessler model may be estimated as 3.7 (saline), 1.3 (LMWH), 1.8 (HMWH), 0.9-1.1 (DET+ LMWH or PZ + LMWH) and 1-1.3 (DET+ HMWH or PZ + HMWH ). Besides, it has been shown that TF was accompanied with significant hypercoagulation of blood: 5’NT activity was increased in 2 time comparatively with normal level. LMWH or HMWH combinations with DET or PZ administration led to normalization of 5’NT level in blood plasma. In arterio-venous shunt model it has been shown that the time of TF was 2 min (saline), that was accompanied with the decrease of blood pressure (on 40-50 mmHg). In this case the time of TF was prolonged in 4 time (LMWH) or 2 time (HMWH) comparatively with saline group 15 min after injection; in 4.5-5 time (DET+ LMWH or PZ + LMWH) or 3-3.5 time (DET + HMWH or PZ + HMWH ) comparatively with saline group 180 min after injection.
Conclusion
Thus we confirmed that LMWH (as one, as in combination with α–adrenoreceptor antagonists) has definite advantages over HMWH. Besides our results show that α–adrenoreceptor antagonists significantly improvement antithrombotic effect of anticoagulant agents (LMWH and HMWH). Therefore the combination of LMWH with selective and nonselective α–adrenoreceptor antagonists may be effective used for prevention of venous thrombosis development and thromboembolia.
Session topic: 34. Thrombosis and vascular biology
Keyword(s): Thrombosis, Heparin, Antithrombotic Therapy, Anticoagulants
Abstract: PB2226
Type: Publication Only
Background
Rethrombosis and thromboembolia are the most common side effects of thrombolytic therapy. One of the possible causes of thrombosis is the entering of thromboplastin in the blood stream. Marker of thromboplastin is an intrinsic membrane glycoprotein 5’-nucleotidase (5’NT) that is present as an enzyme in a wide variety of cells. Recently it was shown that compensatory reaction of haemostasis system by using different fibrinolytic drugs was connected with the stimulation of the sympathetic nervous system. Besides, it is known that selective and nonselective α–adrenoreceptor blocking agents have fibrinolytic and antiplatelet effects. The prevention of thrombosis complication is very important field of pathophysiology and medical practices. Therefore, we studied effects of different α–adrenoreceptor antagonists and the influence of these substances combinations with various anticoagulant and fibrinolytic agents on blood coagulation during many years.
Aims
The study of the influence of low molecular weight heparin (LMWH, 4.4 kD) and high molecular weight heparin (HMWH) and their combinations with different α –adrenoreceptor antagonists (AA) on experimental thrombosis prevention.
Methods
Experiments were carry out on 50 white laboratory rats weighing 200-230 g according to the ethical principles of the Helsinki Declaration. Anticoagulant and antithrombotic effects of LMWH or HMWH were studied in two rat models of thrombosis – thrombosis in v. jugularis (Wessler) and thrombosis in arterio-venous shunt (direct registration of blood pressure). The α–AA digydroergotoxin (DET – 1mg/kg), α1–AA prazosin (PZ – 2mg/kg), LMWH or HMWH (40 USP/kg) were injected in v.jugularis. Saline was administrated in control rat groups. The thrombus were formed 15 or 180 min after substances injected. The degree of thrombus formation (TF) was detected in ball (Wessler model) and by time of TF (arterio-venous shunt model). In blood plasma the activity of 5’NT was detected. The results were processed statistically.
Results
The increase of anticoagulant and antithrombotic effects of LMWH or HMWH by pretreatment of DET or PZ were shown in both animal models of venous thrombosis. The degree of TF by Wessler model may be estimated as 3.7 (saline), 1.3 (LMWH), 1.8 (HMWH), 0.9-1.1 (DET+ LMWH or PZ + LMWH) and 1-1.3 (DET+ HMWH or PZ + HMWH ). Besides, it has been shown that TF was accompanied with significant hypercoagulation of blood: 5’NT activity was increased in 2 time comparatively with normal level. LMWH or HMWH combinations with DET or PZ administration led to normalization of 5’NT level in blood plasma. In arterio-venous shunt model it has been shown that the time of TF was 2 min (saline), that was accompanied with the decrease of blood pressure (on 40-50 mmHg). In this case the time of TF was prolonged in 4 time (LMWH) or 2 time (HMWH) comparatively with saline group 15 min after injection; in 4.5-5 time (DET+ LMWH or PZ + LMWH) or 3-3.5 time (DET + HMWH or PZ + HMWH ) comparatively with saline group 180 min after injection.
Conclusion
Thus we confirmed that LMWH (as one, as in combination with α–adrenoreceptor antagonists) has definite advantages over HMWH. Besides our results show that α–adrenoreceptor antagonists significantly improvement antithrombotic effect of anticoagulant agents (LMWH and HMWH). Therefore the combination of LMWH with selective and nonselective α–adrenoreceptor antagonists may be effective used for prevention of venous thrombosis development and thromboembolia.
Session topic: 34. Thrombosis and vascular biology
Keyword(s): Thrombosis, Heparin, Antithrombotic Therapy, Anticoagulants