A modeling tool to study the combined effects of drug administration and LVAD assistance in pathophysiological circulatory conditions

The aim of this work is to develop a tool to study the effect of sodium nitroprusside (SNP) on hemodynamics in conjunction with baroreflex and mechanical circulatory assistance. To this aim, a numerical model of the pharmacodynamic effect of SNP was developed and inserted into a cardiovascular circulatory model integrated with baroreflex and LVAD (continuous flow pump with atrio-aortic connection)sub-models.

The experiments were carried out in two steps. In the first step the model was verified comparing simulations with experimental data acquired from mongrel dogs on mean arterial pressure (MAP), cardiac output (CO), heart rate (HR), peripheral resistance, and left ventricular properties. In the second step, the combined action of SNP and mechanical circulatory assistance was studied. Data were measured at pump off and at pump on (20000 rpm and 24000 rpm). At pump off, with a 2.5 μg/kg per min SNP infusion in heart failure condition, the MAP was reduced by approximately 8%, CO and HR increased by about 16% and 18%, respectively. In contrast, during assistance (24000 rpm) the changes in MAP, CO and HR were around -9%, +12%, and +20%, respectively. Furthermore, the effects of the drug on hemodynamic parameters at different heart conditions were significantly different. Thus, the model provides insight into the complex interactions between baroreflex, drug infusion, and LVAD and could be a support for clinical decision-making in cardiovascular pathologies.