Efficacy of catheter-based drug delivery in a hybrid in vitro model of cardiac microvascular obstruction with porcine microthrombi.

Microvascular obstruction (MVO) often occurs in ST-elevation myocardial infarction (STEMI) patients after percutaneous coronary intervention (PCI). Diagnosis and treatment of MVO lack appropriate and established procedures. This study focused on two major points by using an in vitro multiscale flow model, which comprised an aortic root model with physiological blood flow and a microfluidic model of the microcirculation with vessel diameters down to 50 µm. First, the influence of porcine microthrombi (MT), injected into the fluidic microchip, on perfusion was investigated. We found that only 43% of all injected MT were fully occlusive. Second, it could also be shown that the maximal concentration of a dye (representing therapeutic agent) during intracoronary infusion could be increased on average by 58%, when proximally occluding the coronary artery by a balloon during drug infusion. The obtained results and insights enhance the understanding of perfusion in MVO-affected microcirculation and could lead to improved treatment methods for MVO patients.

Enhanced Drug Delivery for Cardiac Microvascular Obstruction with an Occlusion-Infusion-Catheter.

Microvascular Obstruction (MVO) is a common consequence of acute myocardial infarction. MVO is underdiagnosed and treatment is often nonspecific and ineffective. A multi-scale in-vitro benchtop 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 [Formula: see text] and 50 µm representing [Formula: see text] 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.

Effect of Collateral Flow on Catheter-Based Assessment of Cardiac Microvascular Obstruction.

Cardiac microvascular obstruction (MVO) associated with acute myocardial infarction (heart attack) is characterized by partial or complete elimination of perfusion in the myocardial microcirculation. A new catheter-based method (CoFI, Controlled Flow Infusion) has recently been developed to diagnose MVO in the catheterization laboratory during acute therapy of the heart attack. A porcine MVO model demonstrates that CoFI can accurately identify the increased hydraulic resistance of the affected microvascular bed. A benchtop microcirculation model was developed and tuned to reproduce in vivo MVO characteristics. The tuned benchtop model was then used to systematically study the effect of different levels of collateral flow. These experiments showed that measurements obtained in the catheter-based method were adversely affected such that collateral flow may be misinterpreted as MVO. Based on further analysis of the measured data, concepts to mitigate the adverse effects were formulated which allow discrimination between collateral flow and MVO.

Intracardiac Turbines Suitable for Catheter-Based Implantation-An Approach to Power Battery and Leadless Cardiac Pacemakers?

OBJECTIVE: Cardiac pacemakers are powered by batteries, which become exhausted after a few years. This is a problem in particular for leadless pacemakers as they are difficult to explant. Thus, autonomous devices powered by energy harvesters are desired. METHODS: We developed an energy harvester for endocardial implantation. The device contains a microgenerator to convert a flexible turbine runner's rotation into electrical energy. The turbine runner is driven by the intracardiac blood flow; a magnetic coupling allows hermetical sealing. The energy harvester has a volume of 0.34 cm3 and a weight of 1.3 g. Computational simulations were performed to assess the hemodynamic impact of the implant. The device was studied on a mock circulation and an in vivo trial was performed in a domestic pig. RESULTS: In this article, we show that an energy harvester with a 2-bladed 14-mm-diameter turbine runner delivers 10.2 ± 4.8 µW under realistic conditions (heart rate 80/min, stroke volume 75 ml) on the bench. An increased output power (>80 µW) and power density (237.1 µW/cm3) can be achieved by higher stroke volumes, increased heart rates, or larger turbine runners. The device was successfully implanted in vivo. CONCLUSION: The device is the first flow-based energy harvester suitable for catheter-based implantation and provides enough energy to power a leadless pacemaker. SIGNIFICANCE: The high power density, the small volume, and the flexible turbine runner blades facilitate the integration of the energy harvester in a pacemaker. This would allow overcoming the need for batteries in leadless pacemakers.