scholarly journals Reaction of hemostasis system in hypercapnic hypoxia after the course of mexidol assessed by the method of thromboelastography

2018 ◽  
Vol 99 (6) ◽  
pp. 936-941
Author(s):  
S V Moskalenko ◽  
I I Shakhmatov ◽  
Yu A Bondarchuk ◽  
O V Alekseeva ◽  
O M Ulitina
Keyword(s):  
Alpha Angle ◽  
Maximum Intensity ◽  
Clot Formation ◽  
Male Rats ◽  
Clot Lysis ◽  
Standard Diet ◽  
Single Exposure ◽  
Average Mass ◽  
Hemostasis System ◽  
Hypercapnic Hypoxia

Aim. To study the reaction of hemostasis system to a single effect of hypercapnic hypoxia of maximum intensity in rats and possibility of correcting hemostasis disorders by means of a preliminary course of an antihypoxant - mexidol. Methods. The study involved sexually mature male rats (48 specimens) of the Wistar line with an average mass of 274.0 ± 32.0 g. The rats were kept on a standard diet, food and water were fed once a day between 10 and 11 hours. In the evening, animals underwent a single hypercapnic hypoxia in a special flow chamber. The state of hypercapnic hypoxia of maximum intensity was modeled at O2 content of 5.0 %, CO2 - 5.0 % during a single 20-minute exposure. As a training regimen, a 30-fold course of mexidol was used, the drug was administered intraperitoneally to rats at a dose of 50 mg/kg for 1.5 hours prior to exposure to hypercapnic hypoxia. Results. After a single exposure to hypercapnic hypoxia of maximum intensity, shortening of the onset of clot formation, an increase of alpha angle, and maximum clot density were recorded. Also, the clot formation time shortened and the maximum clot lysis index increased. With a single exposure to hypercapnic hypoxia of maximum intensity after the course of mexidol, a decrease in the maximum clot density was recorded. Conclusion. A single exposure to hypercapnic hypoxia of maximum intensity was characterized by a shift of hemostatic potential toward hypercoagulability along with fibrinolytic system activation. The course use of antihypoxant mexidol, preceding hypercapnic hypoxia of maximum intensity, significantly reduces the risk of clot formation.

scholarly journals Reaction of the hemostatic system in response to hypercapnic hypoxia of maximum intensity ­depending on different types of preconditioning

2019 ◽  
Vol 100 (4) ◽  
pp. 642-649
Author(s):  
S V Moskalenko ◽  
I I Shakhmatov ◽  
I V Kovalev ◽  
K I Shakhmatova ◽  
V M Vdovin
Keyword(s):  
Anticoagulant Activity ◽  
Maximum Intensity ◽  
Male Rats ◽  
Control Group ◽  
Combined Exposure ◽  
Adaptive Changes ◽  
Hemostasis System ◽  
Hypercapnic Hypoxia ◽  
Ethylmethylhydroxypyridine Succinate ◽  
Plasma Unit

Aim. To study the adaptation reactions of the hemostasis system to hypercapnic hypoxia of maximum intensity in rats subjected to preliminary multiple exposure to ethylmethylhydroxypyridine succinate and hypercapnic hypoxia of submaximal intensity. Methods. In the experiment, Wistar male rats (80 individuals) were used. Training cycles: 30-fold daily exposure to hypercapnic hypoxia of submaximal intensity (20 minutes — 9.0±0.5% O2, 7.0±0.5% CO2); administration of ethylmethylhydroxypyridine succinate (50 mg/kg) to animals for 30 days; combined effects of the two described modes. Tested experimental exposure was simulated as a single hypercapnic hypoxia of maximum intensity (20 minutes — 5.0±0.5% O2, 5.0±0.5% CO2) at the end of each of three 30-day training cycles. Results. Preliminary 30-day exposure to both isolated hypercapnic hypoxia of submaximal intensity and combined exposure to ethylmethylhydroxypyridine succinate contributes to hypocoagulation shift in the hemostasis system and reduces the level of the markers of pre-thrombotic state in response to a single hypercapnic hypoxia of maximum intensity. The state of the hemostasis system after 30-day cycle of isolated use of an antihypoxant is characterized by the inhibition of the vascular-platelet system of the hemostasis system and preserved hypercoagulation shifts in its plasma unit. The obtained results suggest that both preliminary isolated effect of hypercapnic hypoxia of submaximal intensity and the combined effect of hypercapnic hypoxia and ethylmethylhydroxypyridine succinate increase the resistance of the hemostasis system in experimental animals to acute hypercapnic hypoxia of maximum intensity compared to rats of the control group. This was confirmed by the inhibition of the vascular-platelet system, hypocoagulation in the plasma unit, decrease in the level of thrombotic readiness markers and increase in the anticoagulant activity of the blood system compared to the control. At the same time, isolated course administration of ethylmethylhydroxypyridine succinate did not cause the same amount of adaptive changes to maximum intensity hypercapnic hypoxia, since only platelet suppression of the hemostasis and hypocoagulation via the internal coagulation pathway were registered. Conclusion. Isolated exposure of hypercapnic hypoxia of submaximal intensity and its combined exposure with ethylmethylhydroxypyridine succinate increase the resistance of the hemostasis system to acute hypercapnic hypoxia of maximum intensity; isolated course administration of ethylmethylhydroxypyridine succinate does not cause the same amount of adaptive changes.

scholarly journals Reaction of the hemostatic system in response to hypercapnic hypoxia of maximum intensity ­depending on different types of preconditioning

2019 ◽  
Vol 100 (4) ◽  
pp. 642-649
Author(s):  
S V Moskalenko ◽  
I I Shakhmatov ◽  
I V Kovalev ◽  
K I Shakhmatova ◽  
V M Vdovin
Keyword(s):  
Anticoagulant Activity ◽  
Maximum Intensity ◽  
Male Rats ◽  
Control Group ◽  
Combined Exposure ◽  
Adaptive Changes ◽  
Hemostasis System ◽  
Hypercapnic Hypoxia ◽  
Ethylmethylhydroxypyridine Succinate ◽  
Plasma Unit

Aim. To study the adaptation reactions of the hemostasis system to hypercapnic hypoxia of maximum intensity in rats subjected to preliminary multiple exposure to ethylmethylhydroxypyridine succinate and hypercapnic hypoxia of submaximal intensity. Methods. In the experiment, Wistar male rats (80 individuals) were used. Training cycles: 30-fold daily exposure to hypercapnic hypoxia of submaximal intensity (20 minutes — 9.0±0.5% O2, 7.0±0.5% CO2); administration of ethylmethylhydroxypyridine succinate (50 mg/kg) to animals for 30 days; combined effects of the two described modes. Tested experimental exposure was simulated as a single hypercapnic hypoxia of maximum intensity (20 minutes — 5.0±0.5% O2, 5.0±0.5% CO2) at the end of each of three 30-day training cycles. Results. Preliminary 30-day exposure to both isolated hypercapnic hypoxia of submaximal intensity and combined exposure to ethylmethylhydroxypyridine succinate contributes to hypocoagulation shift in the hemostasis system and reduces the level of the markers of pre-thrombotic state in response to a single hypercapnic hypoxia of maximum intensity. The state of the hemostasis system after 30-day cycle of isolated use of an antihypoxant is characterized by the inhibition of the vascular-platelet system of the hemostasis system and preserved hypercoagulation shifts in its plasma unit. The obtained results suggest that both preliminary isolated effect of hypercapnic hypoxia of submaximal intensity and the combined effect of hypercapnic hypoxia and ethylmethylhydroxypyridine succinate increase the resistance of the hemostasis system in experimental animals to acute hypercapnic hypoxia of maximum intensity compared to rats of the control group. This was confirmed by the inhibition of the vascular-platelet system, hypocoagulation in the plasma unit, decrease in the level of thrombotic readiness markers and increase in the anticoagulant activity of the blood system compared to the control. At the same time, isolated course administration of ethylmethylhydroxypyridine succinate did not cause the same amount of adaptive changes to maximum intensity hypercapnic hypoxia, since only platelet suppression of the hemostasis and hypocoagulation via the internal coagulation pathway were registered. Conclusion. Isolated exposure of hypercapnic hypoxia of submaximal intensity and its combined exposure with ethylmethylhydroxypyridine succinate increase the resistance of the hemostasis system to acute hypercapnic hypoxia of maximum intensity; isolated course administration of ethylmethylhydroxypyridine succinate does not cause the same amount of adaptive changes.

scholarly journals Platelet Apoptosis and PAI-1 Content Are Involved in the Procoagulant Profile of Immune Thrombocytopenia Patients Responders to Agonists of Thrombopoietin Receptor.

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3738-3738
Author(s):  
Raul Justo Sanz ◽  
Elena Monzón Manzano ◽  
Ihosvany Fernandez-Bello ◽  
Teresa Álvarez-Roman ◽  
Mónica Martín ◽  
...  
Keyword(s):  
Research Funding ◽  
Immune Thrombocytopenia ◽  
Alpha Angle ◽  
Clot Formation ◽  
Clot Lysis ◽  
Control Group ◽  
Healthy Controls ◽  
Prothrombinase Complex ◽  
Thrombopoietin Receptor ◽  
Pai 1

Abstract Background: The treatment goal for patients with immune thrombocytopenia (ITP) is to raise platelet counts to levels that minimize or stop bleeding. Thrombopoietin receptor agonists (TPO-RAs) have been successfully and extensively employed as second-line therapy for ITP. TPO-RAs, however, have a small but significant increase in the risk of thrombosis. Aim: The aim of this study was to elucidate the mechanisms involved in the procoagulant effect of TPO-RAs. Methods: This is a prospective, observational and transversal study. Eighty-two patients with chronic primary ITP, 40 without treatment for at least six months (UT-ITP) and 42 responders to TPO-RA therapy (64.3% with eltrombopag and 35.7 % with romiplostim) were recruited. One hundred and twelve healthy participants were also included. ROTEM® (naTEM test: only recalcification) was performed on platelet rich plasma adjusted to a platelet count of 25 x 109/L. Clotting time (CT, time from start of measurement until 2 mm of amplitude [in seconds], alpha angle, which reflects the rate of fibrin polymerisation (tangent to the curve at 2 mm amplitude [in degrees]), maximum clot firmness, which reflects the maximum tensile strength of the thrombus (MCF, [in mm]) and LI60, which describes the percentage of maximum clot strength present at 60 min (in %), were recorded. Surface exposure of phosphatidylserine (PS), active caspase-3, -8 or -9 and prothrombinase complex binding to platelets were assessed by flow cytometry. Plasma and platelet levels of PAI-1 were determined by ELISA (eBioscience Ltd., Hatfield, United Kingdom). The effect of TPO and romiplostim on PAI-1 content of MEG-01 cells was evaluated by Western blot. Three MEG-01 cell cultures were initiated simultaneously: control without drugs and treated with either TPO (100 ng/mL) or romiplostim (53 μg/mL). Samples were collected at the start and after 24, 48 and 72 hours to determine the PAI-1 content. The statistical analysis was performed using SPSS 9.0 software (SPSS Inc., Chicago, Illinois, USA). Results: The ROTEM® studies showed significant differences in the dynamics of clot formation when comparing the control with ITP samples. There was a delay in clot formation in the UT-ITP group, as observed by a prolonged CT [expressed as median (p25-p75): control: 516 (490- 633) s; UT-ITP: 938 (914-1348) s, p<0.001], and a diminished alpha angle (mean±SD; control: 61.7±5.6 degrees; UT-ITP: 49.2±7.3 degrees, p<0.05). Nevertheless, samples from patients with UT-ITP reached the same MCF as those from healthy controls (control: 45.3±2.4 mm; UT-ITP: 46.9±3.7 mm). On the other hand, patients with ITP undergoing TPO-RA therapy presented an initial clot formation similar to that of the control group [expressed as median (p25-p75): CT, 672 (598-928) s; alpha angle, 55.8±5.8 degrees] but achieved a higher MCF (53.1±4.5 mm, p<0.05) and a reduced clot lysis after 60 min (control: 91.8±4.0%; UT-ITP: 93.7±4.0%, TPO-RA ITP: 97.6±1.7, p<0.05). Higher values of MCF observed with platelets from ITP patients treated with TPO-RAs might be a consequence of their augmented apoptosis signs: platelets from this group exposed more PS than controls and this situation was accompanied by an increased activity of caspases-3,7, -8 and -9 (Figure 1 A and B). Moreover, platelets from ITP patients on treatment with TPO-RAs bound more prothrombinase complex than platelets from UT-ITP patients and healthy controls (Figure 1 C). Reduced clot lysis observed in ITP patients treated with TPO-RA was due, at least in part, to increased plasma and platelet levels of PAI-1 (Table 1). Increase in platelet content of PAI-1 might be the result of the effect of TPO-RAs during megakaryopoiesis since treatments of MEG-01 cells with TPO or romiplostim induced a 3-fold increase in their endogenous PAI-1 content after an incubation period of 48 hs. Conclusion: The patients with ITP undergoing TPO-RAs therapy presented a procoagulant profile due to the formation of a more fibrinolysis-resistant clot because of increased platelet and plasma PAI-1 levels. Moreover, platelets from this group of patients showed more signs of apoptosis that causes a higher exposure of PS and, consequently, a larger surface for the binding of the prothrombinase complex. Work supported by grant from FIS-FEDER PI15/01457. NB holds a Miguel Servet II (FIS-FEDER CP14/00024). Disclosures Álvarez-Roman: SOBI: Consultancy; NovoNordisk: Consultancy; Shire: Consultancy. Jimenez-Yuste:Grifols: Consultancy, Research Funding; Octapharma: Consultancy, Research Funding; CSL Behring: Consultancy; Bayer: Consultancy, Research Funding; Roche: Consultancy, Research Funding; Shire: Consultancy, Research Funding; Sobi: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; NovoNordisk: Consultancy, Research Funding. Butta:FIS-Fondos FEDER: Research Funding.

scholarly journals Detection of the State of Thrombotic Readiness in Rats under One-Time Suprathreshold Physical Activity of Various Durations by Means of Thromboelastography

2019 ◽  
pp. 460-469
Author(s):  
Alexander A. Blazhko ◽  
Igor I. Shakhmatov ◽  
Igor V. Kovalev ◽  
Valeriy I. Kiselev ◽  
Yuliya A. Bondarchuk ◽  
...  
Keyword(s):  
Physical Activity ◽  
Alpha Angle ◽  
The State ◽  
Clot Formation ◽  
Clot Lysis ◽  
Coagulation Time ◽  
Integrated Method ◽  
Hemostatic System ◽  
The One ◽  
Maximum Clot Firmness

Suprathreshold physical activity causing distress in the organism can lead to the damage of various organs and systems including the hemostatic system. A modern integrated method of the hemostatic system assessment is thromboelastography. The purpose of the present study was to evaluate the state of the hemostatic system under one-time suprathreshold physical activity of various durations by means of thromboelastography. Experimental groups of rats were exposed to 4-hour and 8-hour physical activities in the form of forced running on a moving platform with the speed of 6-8 m/min. Immediately after the one-time physical activity, blood samples taken from rats were examined using the thrombelastograph in the Natem mode for 35 minutes. The 4-hour physical activity caused a reduction in coagulation time (CT) and an increase in the alpha angle and the maximum clot firmness (MCF). After the 8-hour activity, the thrombelastograph registered a reduction in coagulation time (CT), an increase in the alpha angle, a decrease in the clot formation time (CFT), a decrease in the maximum clot firmness (MCF), and a reduction in the maximum clot lysis (ML). The 4-hour physical activity resulted in partial activation of the hemostatic system without changing the fibrinolytic activity of blood plasm. The changes revealed in thromboelastography parameters indicate a high risk of the development of thrombotic readiness. The 8-hour physical activity causes a shift of the hemostatic system parameters in rats towards the increased clot formation: hypercoagulation, fibrinogen and platelet consumption, inhibition of fibrinolysis. The combination of changes in thromboelastogram parameters is indicative of the development of thrombotic readiness

scholarly journals Blood loss and coagulation profile in pregnant and non-pregnant queens undergoing elective ovariohysterectomy

2020 ◽  
pp. 1098612X2095961
Author(s):  
James Mack Fudge ◽  
Bernie Page ◽  
Amy Mackrell ◽  
Inhyung Lee ◽  
Unity Jeffery
Keyword(s):  
Blood Loss ◽  
Whole Blood ◽  
Point Of Care ◽  
Alpha Angle ◽  
Clot Formation ◽  
Clot Lysis ◽  
Intraoperative Blood Loss ◽  
Increased Risk ◽  
Midline Approach ◽  
Clot Formation Time

Objectives The aims of this study were to determine if there is increased risk of intraoperative bleeding in pregnant cats undergoing elective ovariohysterectomy (OHE), and to compare coagulation in queens in various stages of estrus and pregnancy subjected to elective OHE using a whole-blood viscoelastic assay. Methods Intraoperative blood loss was compared between non-pregnant and pregnant cats undergoing elective OHE. Viscoelastic evaluations of whole blood drawn pre- and postoperatively were performed using a point-of-care device measuring clot time (CT), clot formation time (CFT), alpha angle, maximum clot formation (MCF), amplitude at 10 and 20 mins (A10 and A20, respectively), and lysis index at 30 and 45 mins after MCF (LI30 and LI45, respectively). Results One hundred and ninety-three cats underwent OHE by a ventral midline approach. Median blood loss was greater for pregnant cats (2.0 ml, range <0.5–13 ml) than non-pregnant cats (<0.5 ml, range <0.5–15 ml; P <0.0001). Preoperatively, pregnant cats had a shorter median CFT (165 s vs 190.5 s), increased median A10 (31 from 25.5 VCM units) and A20 (38 from 35 VCM units), and a lower median LI45 (99% from 100%) than non-pregnant cats. Postoperatively, A10 and A20 increased, and LI30 and LI45 decreased in both non-pregnant and pregnant queens. In pregnant queens, mean CT also increased postoperatively. Conclusions and relevance Pregnant cats were relatively hypercoagulable and had an increased rate of clot lysis than non-pregnant cats. Intraoperative blood loss was increased in pregnant vs non-pregnant cats, but no clinically relevant bleeding conditions occurred.

scholarly journals FC 015LACK OF PLASMINOGEN RELATES TO A HYPERCOAGULABLE STATE IN MICE WITH EXPERIMENTAL NEPHROTIC SYNDROME

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Mengyun Xiao ◽  
Stefanie Hammer ◽  
Wissam A Khalel ◽  
Lisann Pelzl ◽  
Bernhard N Bohnert ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Alpha Angle ◽  
Formation Time ◽  
Clot Formation ◽  
Hypercoagulable State ◽  
Clot Lysis ◽  
Activity Measurement ◽  
Clotting Time ◽  
Plasminogen Deficiency ◽  
Clot Formation Time

Abstract Background and Aims Urinary excretion of the fibrinolytic enzyme plasminogen has been identified as a characteristic feature of nephrotic syndrome (NS) in both human and experimental mouse models. Lack of plasminogen may lead to a hypercoagulable state and thrombosis, and mice with plasminogen deficiency have been shown to suffer from developing spontaneous thrombosis. However, the role of plasminogen in hypercoagulable state and thrombosis in an experimental nephrotic syndrome has not been investigated before. Method We investigated the relationship between plasminogen and a hypercoagulable state in an inducible nephrotic mouse model with conditional podocyte-specific podocin deletion (Nphs2Δipod * Plg+/+, n=12). The Nphs2Δipod mice with constitutive plasminogen knockout were used as negative plasminogen control (Nphs2Δipod * Plg-/-, n=15). All mice received a daily oral doxycycline administration for 2 weeks for NS induction. The last day of doxycycline treatment was set as day 0. Spot urine was collected daily for proteinuria and urinary plasmin activity measurement. Citrate blood was collected from each mouse before induction of NS, 7 days and 21 days after induction, respectively (Nphs2Δipod * Plg+/+ mice, n=4/timepoint; Nphs2Δipod * Plg-/- mice, n=5/timepoint). A global assessment of coagulation (extrinsic coagulation test, EX test) was examined by ClotPro® system. Besides, fibrinolysis was tested by adding tissue plasminogen activator (TPA test). Results According to the EX test, uninduced mice with plasminogen deficiency showed a significantly reduced clotting time (CT, Plg-/- vs. Plg+/+, 42 ± 1s vs. 54 ± 4s, p=0.0213), and decreased clot formation time (CFT, Plg-/- vs. Plg+/+, 82 ± 5s vs. 206 ± 28s p&lt;0.0001) with a larger alpha-angle (Plg-/- vs. Plg+/+, 75 ± 1° vs. 66 ± 2°, p=0.0041). The maximum clot firmness (MCF) was significantly increased in uninduced plasminogen knockout mice (Plg-/- vs. Plg+/+, 45 ± 0.5mm vs. 32 ± 2.5mm p&lt;0.0001). According to the TPA test, uninduced Nphs2Δipod *Plg-/-mice had a faster velocity of clot formation (α-angle, 75.6 ± 0.2° vs. 66.5 ± 1.6°, p=0.0254) and did not show any clot lysis in contrast to uninduced nphs2Δipod * plg+/+mice. After induction of NS, both Nphs2Δipod * Plg-/-mice and Nphs2Δipod * Plg+/+ mice developed massive proteinuria to a comparable extent (Plg-/- vs. Plg+/+on day 21, 218 ± 46mg/mg crea vs. 203 ± 28mg/mg crea), and plasminuria was detectable in nephrotic nphs2Δipod * plg+/+ mice. With the ongoing loss of plasminogen in the urine, CT and CFT was significantly reduced in nephrotic Nphs2Δipod * Plg+/+ mice. MCF was significantly increased with a faster velocity of clot formation measured by both the EX and TPA test. Moreover, clot lysis was significantly reduced. In nephrotic nphs2Δipod *plg-/-mice at day 21, there was also a tendency towards a decrease in CT, CFT and an increased velocity of clot formation. According to both EX and TPA test, there were no significant differences between the genotypes in nephrotic mice any more. Conclusion The results highlight that loss of plasminogen in the nephrotic state contributes to a hypercoagulable state with shortened clotting time, clot formation time, increased clot firmness, and most strikingly, loss of clot lysis. Changes in nephrotic wild-type mice were similar to mice with constitutive plasminogen deficiency, indicating that loss of plasminogen plays a role in the hypercoagulable state of nephrotic syndrome.

HEMOSTASIOLOGICAL PROFILE IN RATS UNDER SINGLE EXPOSURE TO SUBMAXIMAL AND MAXIMUM HYPERCAPNIC HYPOXIA

2020 ◽  
pp. 127-137
Author(s):  
S.V. Moskalenko ◽  
I.I. Shakhmatov ◽  
V.I. Kiselev ◽  
V.M. Vdovin ◽  
A.A. Blazhko
Keyword(s):  
Blood Plasma ◽  
Anticoagulant Activity ◽  
Male Rats ◽  
Simultaneous Increase ◽  
Fibrinogen Concentration ◽  
Single Exposure ◽  
Platelet Number ◽  
Hypercapnic Hypoxia ◽  
Aggregation Activity ◽  
In Blood Plasma

Hypoxia is the main link in the taxis pathogenesis to most extreme factors. It occurs in many pathological processes. The aim of the work was to study the hemostatic system in rats under a single exposure to submaximal and maximum hypercapnic hypoxia. Materials and Methods. The experiment enrolled 40 Wistar male rats. Single 20-minute hypercapnic hypoxia (HH) was modeled by placing the animals into a chamber with a gas mixture: submaximal HH: O2 – 9 %; CO2 –7 %; maximum HH: O2 – 5 %; CO2 – 5 %. Results. Single submaximal HH was accompanied by a decrease in the platelet number under a constant level of their aggregation activity. Hypercoagulable shift was observed along the internal pathway and at the final stage of coagulation against the decrease in fibrinogen concentration. AT III level decreased, however, there were no changes in blood APR. Single maximum HH led to more pronounced coagulable shifts. Platelet hemostasis responded by a decrease in the platelet number with a simultaneous increase in their aggregation activity. As for coagulation hemostasis, hypercoagulation was recorded at all stages of coagulation. At the same time, fibrinogen concentration in blood plasma decreased, and the level of soluble fibrin-monomer complexes (SFMCs) significantly increased. The authors reported an increase in plasma fibrinolytic activity. Conclusion. Thus, upon a single exposure to submaximal HH, hypercoagulation was not yet accompanied by thrombinemia markers. At the same time, the danger of thrombotic state development remained, since the hypercoagulable shift was recorded against a decrease in blood plasma anticoagulant activity. A further increase in HH intensity was accompanied by deteriorating hemostatic functions of experimental animals, which could be described as a state of thrombotic readiness. A decrease in the anticoagulant level in response to maximum HH exacerbated thrombosis risks. Keywords: hemostasis, hypercapnic hypoxia. Гипоксия выступает в качестве основного звена патогенеза ответной реакции организма на воздействие большинства экстремальных факторов и встречается во многих патологических процессах. Цель работы – изучить состояние системы гемостаза у крыс, подвергшихся однократному воздействию гиперкапнической гипоксии субмаксимальной и максимальной интенсивности. Материалы и методы. В эксперименте использовались крысы-самцы (40 особей) линии «Вистар». Однократная 20-минутная гиперкапническая гипоксия (ГКГ) моделировалась путем помещения животных в камеру, в которую подавалась смесь газов: ГКГ субмаксимальной интенсивности – 9 % О2, 7 % СО2; максимальной – 5 % О2, 5 % СО2. Результаты. Однократная ГКГ субмаксимальной интенсивности сопровождалась снижением количества тромбоцитов при неизменном уровне их агрегационной активности. Гиперкоагуляционный сдвиг отмечался по внутреннему пути и на конечном этапе свертывания на фоне снижения концентрации фибриногена. Уровень АТ III снижался, однако изменений со стороны АРП крови зафиксировано не было. Однократная ГКГ максимальной интенсивности приводила к более выраженным коагулологическим сдвигам. Тромбоцитарный гемостаз отреагировал снижением количества тромбоцитов при одновременном повышении их агрегационной активности. Со стороны коагуляционного гемостаза регистрировалась гиперкоагуляция на всех этапах свертывания. При этом концентрация фибриногена в плазме крови снижалась, уровень РФМК значительно повышался. Было зарегистрировано повышение фибринолитической активности плазмы крови. Выводы. Таким образом, по завершении однократного воздействия ГКГ субмаксимальной интенсивности гиперкоагуляция еще не сопровождалась появлением маркеров тромбинемии. При этом опасность развития тромботического состояния сохранялась, поскольку гиперкоагуляционный сдвиг регистрировался на фоне снижения антикоагулятной активности плазмы крови. Дальнейшее повышение интенсивности воздействия ГКГ сопровождалось ухудшением гемостатического статуса экспериментальных животных, что может быть охарактеризовано как состояние тромботической готовности. Снижение уровня антикоагулянта в ответ на ГКГ максимальной интенсивности увеличивало риск развития тромбообразования. Ключевые слова: гемостаз, гиперкапническая гипоксия.

Feasibility of Recording Clot Lysis with the Thermometric Clot Detector

1974 ◽  
Vol 20 (11) ◽  
pp. 1435-1437 ◽  
Author(s):  
William D Bostick ◽  
Peter W Carr
Keyword(s):  
Detection System ◽  
Clot Formation ◽  
Clot Lysis ◽  
Coagulation Process

Abstract We investigated the possibility of continuously recording the process of clot lysis with a thermometric clot detector. Experiments in which fibrinolytic activators and inhibitors were used demonstrate that the detection system, without any mechanical modifications, is suitable for monitoring the complete coagulation process from clot formation to the ultimate lysis of the clot itself.

Time window-dependent effect of perinatal maternal protein restriction on insulin sensitivity and energy substrate oxidation in adult male offspring

2014 ◽  
Vol 307 (2) ◽  
pp. R184-R197 ◽  
Author(s):  
Aurore Martin Agnoux ◽  
Jean-Philippe Antignac ◽  
Gilles Simard ◽  
Guillaume Poupeau ◽  
Dominique Darmaun ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Insulin Sensitivity ◽  
Adult Male ◽  
Time Window ◽  
Substrate Oxidation ◽  
Male Rats ◽  
Testable Hypothesis ◽  
Integrative Approach ◽  
Composition Analysis ◽  
Standard Diet

Epidemiological and experimental evidence suggests that a suboptimal environment during perinatal life programs offspring susceptibility to the development of metabolic syndrome and Type 2 diabetes. We hypothesized that the lasting impact of perinatal protein deprivation on mitochondrial fuel oxidation and insulin sensitivity would depend on the time window of exposure. To improve our understanding of underlying mechanisms, an integrative approach was used, combining the assessment of insulin sensitivity and untargeted mass spectrometry-based metabolomics in the offspring. A hyperinsulinemic-euglycemic clamp was performed in adult male rats born from dams fed a low-protein diet during gestation and/or lactation, and subsequently exposed to a Western diet (WD) for 10 wk. Metabolomics was combined with targeted acylcarnitine profiling and analysis of liver gene expression to identify markers of adaptation to WD that influence the phenotype outcome evaluated by body composition analysis. At adulthood, offspring of protein-restricted dams had impaired insulin secretion when fed a standard diet. Moreover, rats who demonstrated catch-up growth at weaning displayed higher gluconeogenesis and branched-chain amino acid catabolism, and lower fatty acid β-oxidation compared with control rats. Postweaning exposure of intrauterine growth restriction-born rats to a WD exacerbated incomplete fatty acid β-oxidation and excess fat deposition. Control offspring nursed by protein-restricted mothers showed peculiar low-fat accretion through adulthood and preserved insulin sensitivity even after WD-exposure. Altogether, our findings suggest a testable hypothesis about how maternal diet might influence metabolic outcomes (insulin sensitivity) in the next generation such as mitochondrial overload and/or substrate oxidation inflexibility dependent on the time window of perinatal dietary manipulation.

Effects of high-cholesterol and atherogenic diets on vascular relaxation in spontaneously hypertensive rats

1997 ◽  
Vol 273 (2) ◽  
pp. H647-H654 ◽  
Author(s):  
M. Cappelli-Bigazzi ◽  
S. Rubattu ◽  
C. Battaglia ◽  
R. Russo ◽  
I. Enea ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Function ◽  
Spontaneously Hypertensive Rats ◽  
Vascular Reactivity ◽  
Male Rats ◽  
Standard Diet ◽  
High Cholesterol ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Endothelium Dependent Relaxation

Hypercholesterolemia is associated with more rapid development of atherosclerosis, and hypertension is frequently associated with abnormal vascular function. Therefore, to investigate the role of hypercholesterolemia and hypertension on vascular function, we studied three groups of male rats (aged 6 wk): normotensive Wistar-Kyoto rats (WKY) as a control group and spontaneously hypertensive rats (SHR) receiving either standard diet (SD; SHR-SD) or high-cholesterol (1%) diet (ChD; SHR-ChD). Vascular reactivity was tested on isolated aortic rings at 4 wk and at 3 and 6 mo of diet. At 3 mo, endothelium-dependent relaxation to acetylcholine (ACh) and ADP was significantly reduced in SHR-ChD but not in SHR-SD compared with WKY. At 6 mo, relaxations to ACh were further impaired in both SHR groups compared with WKY. Endothelium-independent vasodilation to nitroglycerin (NTG) was not different in the three groups of animals throughout 6 mo of diet. In additional experiments, we evaluated vascular reactivity in rats fed with ChD enriched with an excess of vitamin D [atherogenic diet (AD)] capable of producing vascular atherosclerotic lesions. In particular, we studied three additional groups of WKY and SHR rats fed with SD, AD, or AD plus a nonhypotensive dose of the calcium antagonist nitrendipine (Nit). Vasodilation to ACh and ADP was significantly blunted in WKY-AD compared with WKY-SD, whereas it was partially improved in WKY-Nit. There were no differences in endothelium-independent relaxation to NTG in the three WKY groups. In contrast, SHR-AD showed a marked reduction of endothelium-dependent and -independent vasodilation, but only endothelium-dependent vasodilation was preserved by addition of Nit to the diet. These data suggest that the development of vascular dysfunction in rat genetic hypertension is accelerated by ChD, in absence of detectable vascular lesions. Our study also shows that AD alters both vascular smooth muscle and endothelium-dependent relaxation. Low doses of Nit partially preserve endothelium-dependent vasodilation but do not affect the impairment of smooth muscle function in these rats.

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