Multimodal cardiovascular model for hemodynamic analysis: Simulation study on mitral valve disorders

Valvular heart diseases are a prevalent cause of cardiovascular morbidity and mortality worldwide, affecting a wide spectrum of the population. In-silico modeling of the cardiovascular system has recently gained recognition as a useful tool in cardiovascular research and clinical applications. Here, we present an in-silico cardiac computational model to analyze the effect and severity of valvular disease on general hemodynamic parameters. We propose a multimodal and multiscale cardiovascular model to simulate and understand the progression of valvular disease associated with the mitral valve. The developed model integrates cardiac electrophysiology with hemodynamic modeling, thus giving a broader and holistic understanding of the effect of disease progression on various parameters like ejection fraction, cardiac output, blood pressure, etc., to assess the severity of mitral valve disorders, naming Mitral Stenosis and Mitral Regurgitation. The model mimics an adult cardiovascular system, comprising a four-chambered heart with systemic, pulmonic circulation. The simulation of the model output comprises regulated pressure, volume, and flow for each heart chamber, valve dynamics, and Photoplethysmogram signal for normal physiological as well as pathological conditions due to mitral valve disorders. The generated physiological parameters are in agreement with published data. Additionally, we have related the simulated left atrium and ventricle dimensions, with the enlargement and hypertrophy in the cardiac chambers of patients with mitral valve disorders, using their Electrocardiogram available in Physionet PTBI dataset. The model also helps to create ‘what if’ scenarios and relevant analysis to study the effect in different hemodynamic parameters for stress or exercise like conditions.

Automated Blood Sampling in a Canine Telemetry Cardiovascular Model

Successful implementation of automated blood sampling (ABS) into a telemetry instrumented canine cardiovascular model provides simultaneous cardiovascular assessment of novel compounds while collecting multiple blood samples for analysis of drug level, cytokines, and biomarkers. Purpose-bred male Beagle dogs (n = 36) were instrumented with a dual-pressure telemetry transmitter and vascular access port. Modifications to acclimation practices, surgical procedures, and housing were required for implementation of ABS in our established cardiovascular canine telemetry colony. These modifications have increased the use and reproducibility of the model by combining early pharmacokinetic and cardiovascular studies, thus achieving both refinement and reduction from a 3R perspective. In addition, the modified model can shorten timelines and reduce the compound requirement in early stages of drug development. This telemetry–ABS model provides an efficient means to quickly identify potential effects on key cardiovascular parameters in a large animal species and to obtain a more complete pharmacokinetic–pharmacodynamic profile for discovery compounds.

A Simple Cardiovascular Model for the Study of Hemorrhagic Shock

Hemorrhagic shock is the number one cause of death on the battlefield and in civilian trauma as well. Mathematical modeling has been applied in this context for decades; however, the formulation of a satisfactory model that is both practical and effective has yet to be achieved. This paper introduces an upgraded version of the 2007 Zenker model for hemorrhagic shock termed the ZenCur model that allows for a better description of the time course of relevant observations. Our study provides a simple but realistic mathematical description of cardiovascular dynamics that may be useful in the assessment and prognosis of hemorrhagic shock. This model is capable of replicating the changes in mean arterial pressure, heart rate, and cardiac output after the onset of bleeding (as observed in four experimental laboratory animals) and achieves a reasonable compromise between an overly detailed depiction of relevant mechanisms, on the one hand, and model simplicity, on the other. The former would require considerable simulations and entail burdensome interpretations. From a clinical standpoint, the goals of the new model are to predict survival and optimize the timing of therapy, in both civilian and military scenarios.

Aortic flow below and visceral circulation during aortic counterpulsation: Evaluation of an in vitro model

Introduction: This study aimed to test a computer-driven cardiovascular model for the evaluation of the visceral flow during intra-aortic balloon pump (IABP) assistance. Methods: The model includes a systemic and pulmonary circulation as well as a heart contraction model. The straight polyurethane tube aorta had a single visceral while four windkessel components mimicked resistance compliance of the brachiocephalic, renal and sub-mesenteric, pulmonary, and systemic circulation. Twelve flow probes were placed in the circuit to measure pressures and flows with the IABP on and off. Results: With the balloon off, the meantime to reach the steady state was 48 ± 16 s; with the balloon on, this figure was 178 ± 20 s. The stability of pressure and flow signals was obtained after 72 ± 11 min. The number of cycles of stability of the system was 93 [86–103]. Measurements were reliable either with samples of 10 or 20 beats. Bland Altman method demonstrated the reliability of measurements. Finally, all measurements were comparable to published in vivo data. Conclusion: The presented mock circulation was reliable and gave values with high accuracy both at baseline and during mechanical assistance. This system allows evaluation of the mesenteric flow during IABP, under different clinical/hemodynamic conditions. Nonetheless, its translational potential needs to be further evaluated