Microvascular Obstruction (MVO) is a common consequence of acute myocardial infarction. MVO is underdiagnosed and treatment is often nonspecific and ineffective. A multi-scalein-vitrobenchtop model was established to investigate drug perfusion in MVO affected microcirculation. The central element of the benchtop model was a fluidic microchip containing channels with diameters between\documentclass[12pt]{minimal}
				\usepackage{amsmath}
				\usepackage{wasysym} 
				\usepackage{amsfonts} 
				\usepackage{amssymb} 
				\usepackage{amsbsy}
				\usepackage{mathrsfs}
				\usepackage{upgreek}
				\setlength{\oddsidemargin}{-69pt}
				\begin{document}$$555$$\end{document}555and 50μm representing\documentclass[12pt]{minimal}
				\usepackage{amsmath}
				\usepackage{wasysym} 
				\usepackage{amsfonts} 
				\usepackage{amssymb} 
				\usepackage{amsbsy}
				\usepackage{mathrsfs}
				\usepackage{upgreek}
				\setlength{\oddsidemargin}{-69pt}
				\begin{document}$$2\%$$\end{document}2%of the microvascular tree fed by the left anterior descending artery (LAD). The outlets of the chip could be closed to mimic MVO. Two methods for intracoronary infusion of pharmacologic agents (simulated by dye) to regions with MVO were investigated using an occlusion-infusion catheter. The first case was a simple, bolus-like infusion into the LAD, whereas the second case consisted of infusion with concomitant proximal occlusion of the LAD phantom with a balloon. Results show that local dye concentration maxima in the chip with MVO were 2.2–3.2 times higher for the case with proximal balloon occlusion than for the conventional infusion method. The cumulated dose could be raised by a factor 4.6–5.2. These results suggest that drug infusion by catheter is more effective if the blood supply to the treated vascular bed is temporarily blocked by a balloon catheter.Supplementary InformationThe online version contains supplementary material available at 10.1007/s10439-023-03142-z.