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Rat Model of Metabolic Disorders: Dynamics of Hemostasis and Endothelial Function Changes

T. Obergan1, L. Lyapina1, M. Grigorjeva1, T. Shubina1

1Lomonosov Moscow State University, Moscow, Russian Federation

Abstract Number: PB0037

Meeting: ISTH 2021 Congress

Theme: Coagulation and Natural Anticoagulants » Animal Models in Thrombosis and Hemostasis

Background: Metabolic disorders resulting from the consumption of rich-fat and rich-carbohydrates foods are accompanied by hypercoagulation, endothelial dysfunction and, as a result, the occurrence of thrombotic complications. Rodent models are used to improve the understanding of the causes and progression of these diseases, as well as to create therapeutic methods for their correction.

Aims: To evaluate changes of the hemostatic system and endothelial function in rats with metabolic disorders induced by a high-calorie diet, both with and without additional administration of L-NAME (endothelial synthase blocker).

Methods: Metabolic disorders were induced in adult male Wistar rats by a high-calorie diet (HСD, 3840 kcal/kg, 130% of standard feed) and 10% glucose solution as a drink. At 43rd day of experiment, to enhance endothelial dysfunction, HCD-rats (group 3) were performed intragastric administration of L-NAME (10 mg/kg, once daily, 5 days). Normal animals (group 1, control) and HCD-rats without L-NAME (group 2) received 0.85% saline. At 48th and 55th day of HCD blood samples were collected to assess platelet aggregation (PA), anticoagulant activity (APTT test), coagulation factor XIIIa (FXIIIa) and tissue plasminogen activator (t-PA) activities.

Results: As shown in table 1, at 48th day HСD-rats had hypercoagulation (APTT decreased to 88% vs. control), increased values of PA and FXIIIa (115% and 120% vs. control, respectively) and impaired endothelial function (reduced t-PA activity to 72% vs. control), which persisted until the 55th day of experiment. The L-NAME  introduction further enhanced the blood clotting potential (Group 3): PA, APTT and FXIIIa were 136, 80 and 113% vs. HCD-rats, respectively. This was accompanied by a more pronounced decrease in endothelial function (t-PA – 68% vs. control), which increased 7 days after discontinuation of L-NAME treatment (75% vs. HCD- rats).

Parameters  Day of experiment Group 1
Normal rats (control)
(n = 10)
Group 2
HCD
(n = 10)
Group 3
HCD + L-NAME
(n = 10)
P2-3-value
PA (%) Day 48 100 ± 4.8 115 ± 12* 157 ± 18* < 0.05
Day 55 100 ± 9.4 124 ± 14* 131 ± 12* < 0.05
APTT (sec) Day 48 31.5 ± 6.9 27.7 ± 4.2*  22.3 ± 2.2*  < 0.05
Day 55 39.8 ± 8.4 33.4 ± 5.2*  33.2 ± 2.2*  NS
FXIIIa (U/ml) Day 48 71.7 ± 12.1 86.0 ± 4.1*  97.5 ± 4.4*  < 0.05
Day 55 65.0 ± 10.8 86.5 ± 5.3*  112.4 ± 8.0*  < 0.05
t-PA (mm2) Day 48 42.0 ± 10.6 30.2 ± 4.0*  28.4 ± 0.8*  NS
Day 55 55.8 ± 5.3 33.4 ± 4.2*  25.0 ± 2.4*  < 0.05
 * p1 < 0.05 – significance of differences from Control (Group 1);
  p2-3 – significance of differences between groups 2 and 3, NS – not significant

Hemostasis parameters in rat blood plasma on the 48th and 55th days of the experiment (M ± SD).

Conclusions: Thus, the proposed experimental model can be useful in the study of the hemostasis disorders that occur in metabolic diseases.

To cite this abstract in AMA style:

Obergan T, Lyapina L, Grigorjeva M, Shubina T. Rat Model of Metabolic Disorders: Dynamics of Hemostasis and Endothelial Function Changes [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/rat-model-of-metabolic-disorders-dynamics-of-hemostasis-and-endothelial-function-changes/. Accessed May 20, 2022.

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