Rösch, Yannick Pascal (2023). Efficiency of intracoronary drug infusion into myocardial microcirculation with microvascular obstruction: in vitro study with a multiscale flow model. (Thesis). Universität Bern, Bern
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Abstract
Healthy coronary circulation is crucial for the heart, and thus for a person’s health. The treatment of acute myocardial infarction (MI), one of the major reasons for death, has greatly improved over the last decades. Percutaneous coronary intervention (PCI) is a standardised procedure where a stent is used to reopen MI-patients’ blocked coronary arteries. Re-establishing flow in the macrocirculation was a long time in the focus of MI-research. Poor patient outcome is today often linked to impaired microcirculation after the MI. Myocardial microvascular obstruction (MVO) describes the occlusion of vessels of the microvasculature caused by distal embolisation with microthrombi, mostly smaller than 120 μm. About half of all ST elevation MI (STEMI) patients are reported to show MVO after PCI. The prognostic outcome of patients with MVO is up to half as good as for patients without. Treatment of MVO is a key issue to be addressed in MI treatment. This study addressed this need by establishing an in vitro multiscale benchtop model, representing the coronary circulation by starting with physiological blood flow in an aortic root phantom and going down to the microcirculation of the left anterior descending coronary artery (LAD). A morphologically correct microchip was used to investigate drug distribution in vessels between 700 μm and 50 μm. Due to the small scale, only pharmaceutical approaches are possible. So far, no therapies convinced. Failing due to fluid dynamic reasons is suspected. Different dye infusion protocols (representing intracoronary infusion of pharmaceutical agents) were tested to investigate local flow conditions in MVO-affected regions and to quantify drug delivery efficiency. Both, a simple MVO model with plugged outlets and an enhanced MVO model using real porcine microthrombi was used. Basic knowledge about microthrombi causing occlusions could be gained. A multi-lumen occlusion infusion catheter was used for intracoronary infusion, while proximally occluding the coronary artery by inflating its balloon. Like this, the maximal drug concentration, as well as the cumulated drug dose, could be improved by enabling a wash-in effect driven by the intramyocardial pump effect. Depending on the MVO model used, up to three times higher maximal drug concentrations and up to five times higher cumulated doses could be obtained. Further, studies to investigate the effect of collateral flow, bypassing the balloon occlusion, and optimising the infusion protocol were performed. While the collateral flow led to a significant decrease of the evaluated values, lower infusion rates showed to be beneficial to increase the two defined measures, respectively to decrease the needed dose. The obtained results and findings demonstrate the beneficial effect of performing proximal vessel occlusion by balloon inflation for simultaneous intracoronary drug infusion to increase the local concentration of therapeutic agents and reach dead-ended vessel obstructions which otherwise would not be reached by the therapeutic agents. Future treatment strategies for MVO may benefit from the gained knowledge and could lead to huge improvements in patients outcome.
| Item Type: | Thesis |
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| Dissertation Type: | Single |
| Date of Defense: | 21 March 2023 |
| Subjects: | 500 Science > 570 Life sciences; biology 600 Technology > 610 Medicine & health |
| Institute / Center: | 04 Faculty of Medicine 10 Strategic Research Centers > ARTORG Center for Biomedical Engineering Research |
| Depositing User: | Hammer Igor |
| Date Deposited: | 15 Jan 2025 09:32 |
| Last Modified: | 15 Jan 2025 23:25 |
| URI: | https://boristheses.unibe.ch/id/eprint/5742 |
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