A simplified mesoscale 3D model for characterizing fibrinolysis under flow conditions.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
22 08 2023
22 08 2023
Historique:
received:
25
05
2023
accepted:
19
08
2023
medline:
24
8
2023
pubmed:
23
8
2023
entrez:
22
8
2023
Statut:
epublish
Résumé
One of the routine clinical treatments to eliminate ischemic stroke thrombi is injecting a biochemical product into the patient's bloodstream, which breaks down the thrombi's fibrin fibers: intravenous or intravascular thrombolysis. However, this procedure is not without risk for the patient; the worst circumstances can cause a brain hemorrhage or embolism that can be fatal. Improvement in patient management drastically reduced these risks, and patients who benefited from thrombolysis soon after the onset of the stroke have a significantly better 3-month prognosis, but treatment success is highly variable. The causes of this variability remain unclear, and it is likely that some fundamental aspects still require thorough investigations. For that reason, we conducted in vitro flow-driven fibrinolysis experiments to study pure fibrin thrombi breakdown in controlled conditions and observed that the lysis front evolved non-linearly in time. To understand these results, we developed an analytical 1D lysis model in which the thrombus is considered a porous medium. The lytic cascade is reduced to a second-order reaction involving fibrin and a surrogate pro-fibrinolytic agent. The model was able to reproduce the observed lysis evolution under the assumptions of constant fluid velocity and lysis occurring only at the front. For adding complexity, such as clot heterogeneity or complex flow conditions, we propose a 3-dimensional mesoscopic numerical model of blood flow and fibrinolysis, which validates the analytical model's results. Such a numerical model could help us better understand the spatial evolution of the thrombi breakdown, extract the most relevant physiological parameters to lysis efficiency, and possibly explain the failure of the clinical treatment. These findings suggest that even though real-world fibrinolysis is a complex biological process, a simplified model can recover the main features of lysis evolution.
Identifiants
pubmed: 37608073
doi: 10.1038/s41598-023-40973-1
pii: 10.1038/s41598-023-40973-1
pmc: PMC10444897
doi:
Substances chimiques
Fibrin
9001-31-4
Fibrinolytic Agents
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
13681Investigateurs
Charles Majoie
(C)
Ed van Bavel
(E)
Henk Marquering
(H)
Nerea Arrarte-Terreros
(N)
Praneeta Konduri
(P)
Sissy Georgakopoulou
(S)
Yvo Roos
(Y)
Alfons Hoekstra
(A)
Raymond Padmos
(R)
Victor Azizi
(V)
Claire Miller
(C)
Max van der Kolk
(M)
Aad van der Lugt
(A)
Diederik W J Dippel
(DWJ)
Hester L Lingsma
(HL)
Nikki Boodt
(N)
Noor Samuels
(N)
Stephen Payne
(S)
Tamas Jozsa
(T)
Wahbi K El-Bouri
(WK)
Michael Gilvarry
(M)
Ray McCarthy
(R)
Sharon Duffy
(S)
Anushree Dwivedi
(A)
Behrooz Fereidoonnezhad
(B)
Kevin Moerman
(K)
Patrick McGarry
(P)
Senna Staessens
(S)
Simon F de Meyer
(SF)
Sarah Vandelanotte
(S)
Francesco Migliavacca
(F)
Gabriele Dubini
(G)
Giulia Luraghi
(G)
Jose Felix Rodriguez Matas
(JF)
Sara Bridio
(S)
Bastien Chopard
(B)
Franck Raynaud
(F)
Rémy Petkantchin
(R)
Vanessa Blanc-Guillemaud
(V)
Mikhail Panteleev
(M)
Alexey Shibeko
(A)
Karim Zouaoui Boudjeltia
(K)
Commentaires et corrections
Type : ErratumIn
Informations de copyright
© 2023. Springer Nature Limited.
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