Table 1.

PE modelling by blood clots induction in vivo.

№	Animal species	Blood clots agents		Aim of study	Administration vessel	Study duration	CTEPH pathway possibility	Authors
		Substance/action	Substance/action
1	Mice	Collagen + epinephrine	Collagen – 0,8 μg/g; Epinephrine – 60 μg/kg	Studying of catestatin role in blood clots	Inferior vena cava	30 min	–	[100]
2	Mice	Thrombin	20 U	Studying of gelsolin role in PE prevention	Tail vein	15 min	–	[101]
3	Mice	Collagen + epinephrine	Collagen – 400 μg/kg; Epinephrine – 60 μg/kg	Studying of functional role of platelet isoform CD45	retro-orbital sinus	Acute study (After respiratory distress) < 300 s	–	[102]
4	Mice	Collagen + epinephrine	Collagen – 400 μg/kg; Epinephrine – 60 μg/kg	Definition of functional role of ELMO1 peptide in platelets	Intravenous (n/d)	Acute study (After respiratory distress)	–	[103]
5	Mice	Application of ferric chloride (III)-(soaked filter paper) on femoral vein	Size of filter paper - 1 х 2 mm. FeCl3 concentration– 1,8%. Exposure time – 5 min	Studying of generation rate, stability and embolization risk in case of factor V Leiden (FVL) variant	Femoral vein	2 h	–	[31]
6	Mice	Collagen + epinephrine	Collagen – 280 μg/kg; Epinephrine – 29 μg/kg	Studying of inhibitor tyrosineproteinkinase MER effectiveness in platelets inactivation and blood clots prevention	Intravenous (n/d)	15 min	–	[104]
7	Mice	1) Thromboplastin 2) Collagen + epinephrine	Thromboplastin – 5 μL; Collagen – 64 μg/kg; Epinephrine – 5,4 μg/kg	Studying of platelets TLT-1 receptor role of immune origin hemorrhage	Intravenous (n/d)	30 min	–	[105]
8	Mice	Collagen/2MeSADP + epinephrine	Collagen – 400 μg/kg; 2MeSADP – 20 μg/kg; Epinephrine – 30 μg/kg	Studying of platelets activation mechanisms in case of hemostasis	retro-orbital sinus/Inferior vena cava	Acute study (After respiratory distress)	–	[106]
9	Mice	Collagen + epinephrine	Collagen – 430 μg/kg; Epinephrine – 20 μg/kg	Studying of glucose metabolism effect on platelets function regulation	Intravenous (n/d)	25 min	–	[14]
10	Mice	Collagen + epinephrine	Collagen – 500 μg/kg; Epinephrine – 50 μg/kg	Studying of thrombin inhibitor anticoagulant potency in PE prevention	Tail vein	15 min	–	[107]
11	Mice	Thromboplastin	7,5 μL/g	Studying of the vaccination anticoagulant properties to factor XI in thrombosis prevention	Intravenous (n/d)	3 min	–	[8]
12	Mice	Collagen + epinephrine	Collagen – 0,6 μg/g; Epinephrine – 0,2 μg/g	Study of the thromboxane receptor antagonist antiplatelet properties in PE prevention	Tail vein	Acute study (After respiratory and heartbeat distress)	–	[17]
13	Mice	Collagen + epinephrine	Collagen – 500 μg/kg; Epinephrine – 50 μg/kg	Studying of the antithrombotic and anticoagulant activity of alkaloids Scolopendra subspinipes mutilans	Tail vein	15 min	–	[108]
14	Mice	1) Tissue factor (human recombinant) with phospholipids and calcium 2) High molecular polyphosphate	Till 80% mortality after 20 min after administration	Assessment of protein S mutation role in the development of venous blood clots in PROS1 knockout mice	Inferior vena cava	20 min	–	[13]
15	Mice	Collagen + epinephrine	Collagen – 0,5 μg/kg; Epinephrine – 0,06 μg/kg	Studying of the limiglydol antiplatelet properties in PE prevention	Tail vein	1 day	–	[109]
16	Mice	Splenectomy followed after 1 month narrowing of the inferior vena cava lumen, by ligation	–	Studying of splenectomy role in CTEPH formation	–	1–28 days	CTEPH +/- (after 28 days pressure in PA wasn't measured)	[92]
17	Mice	Thrombin	1500 IU/kg body weight	Studying of the antithrombotic properties of N-acylhydrazone	Tail vein	15 min	–	[28]
18	Mice	Collagen + epinephrine/collagen + epinephrine + amyloid β	Collagen – 1000 μg/kg; Epinephrine – 10 μg/kg; Amyloid β – 2,5 mg/kg	Studying of amyloid β role in thrombosis	Tail vein	15 min	–	[15]
19	Mice	Thrombin	1250 IU/kg body weight	Evaluation of the nanocarrier effectiveness for enhancing oral delivery of enoxaparin	Tail vein	15 min	–	[9]
20	Mice	1. Collagen + norepinephrine 2. Thrombin	1. Collagen – 500 μg/kg; norepinephrine – 80 μg/kg. 2. Thrombin - 2000 IU	Studying of the antithrombotic properties of N-acylhydrazone	Intravenous (n/d)	15 min	–	[11]
21	Mice	Thromboplastin	1–1,33 mg/mice	Testing of thrombosis diagnostic systems	Tail vein	30 min	–	[110]
22	Mice	Collagen	Collagen – 0,4 mg/kg	Studying of the anopheline antiplatelet properties in the PE prevention	Tail vein	1 h	–	[21]
23	Mice	Collagen + epinephrine	Collagen – 80 mg/kg; Epinephrine – 1 mg/kg	Research on the antiplatelet properties of argan oil	Tail vein	15 min	–	[26]
24	Mice	Collagen	0,075 μg/g body weight	Study of the thrombomodulin anticoagulant effect	external jugular vein	1 h	–	[7]
25	Mice	Collagen + epinephrine	Collagen – 500 μg/kg; Epinephrine – 50 μg/kg	Evaluation of the antithrombotic properties of Ginkgo biloba and cilostazol combination	Tail vein	15 min	–	[22]
26	Mice	Neutrophil elastase + collagen-induced arthritis	Neutrophil elastase – 5 U/kg. 2 times per day administration during 3 days	Studying of the neutrophilic elastase role in the PE development. Evaluation of the recombinant soluble thrombomodulin effects in reducing the PE risks.	Tail vein	4 days after last injection	–	[30]
27	Mice	Collagen + epinephrine/U46619	Collagen – 12,5 μg/kg; Epinephrine – 0,075 μg/kg; U46619 – 0,2 mg/kg	Study of the NO-releasing statin antithrombotic properties of	Intravenous (n/d)	15 min	–	[23]
28	Mice	Thromboplastin	Thromboplastin – 65 μL/kg or 140 μL/kg	Studying of CD39 antiplatelet properties on liposomes in the PE prevention	Jugular vein	30 min	–	[111]
29	Mice	Collagen III type + epinephrine	Collagen – 100 mg/kg; Epinephrine – 90 μg/kg	Investigation of the type III collagen derivatives antithrombotic properties	Jugular vein	8 min	–	[25]
30	Mice	Collagen + epinephrine	Collagen – 800 μg/kg; Epinephrine – 60 μg/kg	Studying of the α2A-adrenergic receptors role in platelet activation	Jugular vein	5 min	–	[112]
31	Mice	ADP/NE + ADP	NE – 10 μg/mouse; АДФ – 28 mg/100 g	Studying of the neutrophilic elastase role in the PE development	Intravenous (n/d)	Acute experiment (n/d)	–	[27]
32	Mice	Collagen + epinephrine	Collagen – 12,5 μg/mouse Epinephrine – 0,075 μg/mouse	Investigation of the combination of nitroaspirin and clopidogrel antiplatelet properties in the PE prevention	Intravenous (n/d)	2 min	–	[113]
33	Mice	Collagen + epinephrine/U46619 — agonist to А2 thromboxane receptors	Collagen - 12,5 μg/kg; Epinephrine – 0,075 μg/kg U46619 – 0,2 μg/kg	Studying of the NO-releasing statin antithrombotic properties	Intravenous (n/d)	15 min	–	[24]
34	Mice	Collagen + epinephrine/collagen	Collagen – 25/12/6/3 μg; Epinephrine – 1 μg	Studying of the ɑ2β1 integrin role in the platelet aggregation and thrombus formation	Right Jugular vein	3 min	–	[19]
35	Mice	Thrombin	It was counted as a 90% mortality dose	Studying of low molecular weight heparins anticoagulant action mechanisms	Tail vein	15 min	–	[114]
36	Mice	Thrombin	1250 IU/kg body weight	Investigation of the protein C anticoagulant properties in blood clots prevention	Tail vein	15 min	–	[29]
37	Mice	Collagen + epinephrine	collagen – 400 μg/kg; epinephrine – 50 μg/kg	Study of the glycoprotein IIb/IIIa antagonist antiplatelet properties in the PE prevention	Tail vein	15 min	–	[16]
38	Mice	ADP	300 μg/g body weight	Assessment of the drug antithrombotic properties	Tail vein	10 min	–	[12]
39	Mice	Collagen + epinephrine	collagen – 25 μg; epinephrine – 1,5 μg	Evaluation of the antithrombotic drugs effectiveness in the PE prevention	Tail vein	3 min	–	[10]
40	Mice and rabbits	Mice: human thrombin/collagen + epinephrine; Rabbits: thrombin/ADP/platelets activating factor	Mice: human thrombin 1250 IU/kg, collagen 1,25 mg/kg, epinephrine 75 μg/kg Rabbits: thrombin 10/20 IU/kg or ADP 20 μg/kg or platelets activating factor – 50 ng/kg.	Studying of the anticoagulant and antiplatelet properties of defibrotide	Mice – tail vein; Rabbits – marginal auricular vein	Mice – 15 min; Rabbits – 5 min	–	[20]
41	Mice	Thrombin	Thrombin (0, 25, 50, 75 IU/mouse)	Studying of the thrombomodulin anticoagulant properties in the PE prevention	Tail vein	15 min	–	[115]
42	Mice	Thrombin	3,8–15 IU/mouse	Studying of the thrombomodulin role in the PE pathogenesis	Tail vein	1 h	–	[116]
43	Mice	АDP/collagen/arachidonate	ADP – 400 mg/kg; Collagen – 25 mg/kg; Arachidonate – 90 mg/kg	Studying of the Agrimonia pilosa extract antiplatelet properties in the PE prevention	Intravenous (n/d)	3 min	–	[18]

Note: ADP — adenosinediphosphate, i/v — intravenous administration, IU — international unit, PE — pulmonary embolism, CTEPH — chronic thromboembolic pulmonary hypertension, 2MeSADP — 2-methylthio-adenosine-5′-diphosphate, n/d — no data, NO — nitrogen oxide (II), NE — neutrophil elastase, U46619 — 9,11-dideoxy-11а,9а-epoxymethanoprostaglandin F2a.