Collaterals improve recanalization in acute ischemic stroke patients treated with intravenous thrombolysis, but the mechanisms are poorly understood. To investigate it, an in vitro flow model of the middle cerebral artery was developed with or without collaterals. An occlusion was achieved using human blood clots. Recanalization time, thrombolysis (clot length decrease and red blood cell (RBC) release), pressure gradient across the clot and clot compaction were measured. Results showed that with or without collateral alteplase-treated RBC dominant clots showed recanalization time 98±23 min vs 130±35 min (difference 32 min, 95% CI -6-58 min), relative clot reduction 31.8±14.9% vs 30.3±13.2% (difference 1.5%, 95% CI 10.4-13.4%) and RBC release 0.30±0.07 vs 0.27±0.09 (difference 0.03, 95% CI 0.04-0.10). Similar results were observed with fibrin-dominant clots. In RBC dominant clots, the presence vs absence of collateral caused different pressure gradients across the clot 0.41±0.09 vs 0.70±0.09 mmHg (difference 0.29 mmHg, 95% CI -0.17-0.41 mmHg), and caused the reduction of initial clot compaction by 5%. These findings align with observations in patients, where collaterals shortened recanalization time. However, collaterals did not increase thrombolysis. Instead, they decreased the pressure gradient across the clot, resulting in less clot compaction and easier distal displacement of the clot.

• MeSH
• arteria cerebri media účinky léků   patofyziologie   diagnostické zobrazování   MeSH
• erytrocyty účinky léků   MeSH
• fibrinolytika terapeutické užití   farmakologie   MeSH
• ischemická cévní mozková příhoda * farmakoterapie   patofyziologie   MeSH
• kolaterální oběh * účinky léků   MeSH
• lidé MeSH
• tkáňový aktivátor plazminogenu terapeutické užití   farmakologie   MeSH
• trombolytická terapie metody   MeSH
• trombóza farmakoterapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• fibrinolytika MeSH
• tkáňový aktivátor plazminogenu MeSH

On-chip vascular microfluidic models provide a great tool to study aspects of cardiovascular diseases in vitro. To produce such models, polydimethylsiloxane (PDMS) has been the most widely used material. For biological applications, its hydrophobic surface has to be modified. The major approach has been plasma-based surface oxidation, which has been very challenging in the case of channels enclosed within a microfluidic chip. The preparation of the chip combined a 3D-printed mold with soft lithography and commonly available materials. We have introduced the high-frequency low-pressure air-plasma surface modification of seamless channels enclosed within a PDMS microfluidic chip. The plasma treatment modified the luminal surface more uniformly than in previous works. Such a setup enabled a higher degree of design freedom and a possibility of rapid prototyping. Further, plasma treatment in combination with collagen IV coating created a biomimetic surface for efficient adhesion of vascular endothelial cells as well as promoted long-term cell culture stability under flow. The cells within the channels were highly viable and showed physiological behavior, confirming the benefit of the presented surface modification.

• Klíčová slova
• 3D printing, PDMS, endothelial cell, in vitro model, plasma oxidation, surface modification,
• MeSH
• buněčné kultury MeSH
• cévní endotel * MeSH
• endoteliální buňky * MeSH
• hydrofobní a hydrofilní interakce MeSH
• mikrofluidika MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH