Development of in vitro microfluidic models to study endothelial responses to pulsatility with different mechanical circulatory support devices.

Continuous-flow ventricular assist devices (CFVAD) and counterpulsation devices (CPD) are used to treat heart failure (HF). CFVAD can diminish pulsatility, but pulsatile modes have been implemented to increase vascular pulsatility. The effects of CFVAD in a pulsatile mode and CPD support on the function of endothelial cells (ECs) are yet to be investigated. In this study, two in vitro microfluidic models for culturing ECs are proposed to reproduce blood pressure (BP) and wall shear stress (WSS) on the arterial endothelium while using these medical devices. The layout and parameters of the two microfluidic systems were optimized based on the principle of hemodynamic similarity to efficiently simulate physiological conditions. Moreover, the unique design of the double-pump and double afterload systems could successfully reproduce the working mode of CPDs in an in vitro microfluidic system. The performance of the two systems was verified by numerical simulations and in vitro experiments. BP and WSS under HF, CFVAD in pulsatile modes, and CPD were reproduced accurately in the systems, and these induced signals improved the expression of Ca2+, NO, and reactive oxygen species in ECs, proving that CPD may be effective in normalizing endothelial function and replacing CFVAD to a certain extent to treat non-severe HF. This method offers an important tool for the study of cell mechanobiology and a key experimental basis for exploring the potential value of mechanical circulatory support devices in reducing adverse events and improving outcomes in the treatment of HF in the future.

A Flow Sensor-Based Suction-Index Control Strategy for Rotary Left Ventricular Assist Devices.

Rotary left ventricular assist devices (LVAD) have emerged as a long-term treatment option for patients with advanced heart failure. LVADs need to maintain sufficient physiological perfusion while avoiding left ventricular myocardial damage due to suction at the LVAD inlet. To achieve these objectives, a control algorithm that utilizes a calculated suction index from measured pump flow (SIMPF) is proposed. This algorithm maintained a reference, user-defined SIMPF value, and was evaluated using an in silico model of the human circulatory system coupled to an axial or mixed flow LVAD with 5-10% uniformly distributed measurement noise added to flow sensors. Efficacy of the SIMPF algorithm was compared to a constant pump speed control strategy currently used clinically, and control algorithms proposed in the literature including differential pump speed control, left ventricular end-diastolic pressure control, mean aortic pressure control, and differential pressure control during (1) rest and exercise states; (2) rapid, eight-fold augmentation of pulmonary vascular resistance for (1); and (3) rapid change in physiologic states between rest and exercise. Maintaining SIMPF simultaneously provided sufficient physiological perfusion and avoided ventricular suction. Performance of the SIMPF algorithm was superior to the compared control strategies for both types of LVAD, demonstrating pump independence of the SIMPF algorithm.

Study on the hemodynamic effects of different pulsatile working modes of a rotary blood pump using a microfluidic platform that realizes in vitro cell culture effectively.

Rotary blood pumps (RBPs) operating at a constant speed generate non-physiologic blood pressure and flow rate, which can cause endothelial dysfunction, leading to adverse clinical events in peripheral blood vessels and other organs. Notably, pulsatile working modes of the RBP can increase vascular pulsatility to improve arterial endothelial function. However, the laws and related mechanisms of differentially regulating arterial endothelial function under different pulsatile working modes are still unclear. This knowledge gap hinders the optimal selection of the RBP working modes. To address these issues, this study developed a multi-element in vitro endothelial cell culture system (ECCS), which could realize in vitro cell culture effectively and accurately reproduce blood pressure, shear stress, and circumferential strain in the arterial endothelial microenvironment. Performance of this proposed ECCS was validated with numerical simulation and flow experiments. Subsequently, this study investigated the effects of four different pulsation frequency modes that change once every 1-4-fold cardiac cycles (80, 40, 80/3, and 20 cycles per min, respectively) of the RBP on the expression of nitric oxide (NO) and reactive oxygen species (ROS) in endothelial cells. Results indicated that the 2-fold and 3-fold cardiac cycles significantly increased the production of NO and prevented the excessive generation of ROS, potentially minimizing the occurrence of endothelial dysfunction and related adverse events during the RBP support, and were consistent with animal study findings. In general, this study may provide a scientific basis for the optimal selection of the RBP working modes and potential treatment options for heart failure.