Lung assist devices influence cardio-energetic parameters: Numerical simulation study.

We aim at an analysis of the effects mechanical ventilators (MVs) and thoracic artificial lungs (TALs) will have on the cardiovascular system, especially on important quantities, such as left and right ventricular external work (EW), pressure-volume area (PVA) and cardiac mechanical efficiency (CME). Our analyses are based on simulation studies which were carried out by using our CARDIOSIM(©) software simulator. At first, we carried out simulation studies of patients undergoing mechanical ventilation (MV) without a thoracic artificial lung (TAL). Subsequently, we conducted simulation studies of patients who had been provided with a TAL, but did not undergo MV. We aimed at describing the patient's physiological characteristics and their variations with time, such as EW, PVA, CME, cardiac output (CO) and mean pulmonary arterial/venous pressure (PAP/PVP). We were starting with a simulation run under well-defined initial conditions which was followed by simulation runs for a wide range of mean intrathoracic pressure settings. Our simulations of MV without TAL showed that for mean intrathoracic pressure settings from negative (-4 mmHg) to positive (+5 mmHg) values, the left and right ventricular EW and PVA, right ventricular CME and CO decreased, whereas left ventricular CME and the PAP increased. The simulation studies of patients with a TAL, comprised all the usual TAL arrangements, viz. configurations "in series" and in parallel with the natural lung and, moreover, hybrid configurations. The main objective of the simulation studies was, as before, the assessment of the hemodynamic response to the application of a TAL. We could for instance show that, in case of an "in series" configuration, a reduction (an increase) in left (right) ventricular EW and PVA values occurred, whereas the best performance in terms of CO can be achieved in the case of an in parallel configuration.

The role of extracellular conditions during CaCo-2 cells growth: a preliminary study for numerical model validation.

OBJECTIVES: One important limitation in cell therapy protocols, and regenerative medicine (an innovative and promising strategy for different pathologies treatment), is the lack of knowledge about cells engraftment, proliferation and differentiation. In order to allow an efficient and successful cell transplant, it is necessary to predict the logistics, economic and timing issues during cellular injection. It has been reported that several parameters, such as cells number, temperature and extracellular pH (pH0) value can influence metabolic pathways and cellular growth. Numerical analysis and model can help to reduce and understand the effects of the above environmental conditions on cell survival. The aim of this paper is to develop the first step of cells transplantation in order to identify "in vitro", which parameters can be useful to develop and validate a numerical model, able to evaluate "in vivo" cells engraftment and proliferation. MATERIAL AND METHODS: We studied the variation of extracellular parameters--such as medium volume, buffer system, nutrient concentrations and temperature on human colon carcinoma cells (CaCo-2) "in vitro culture"--pursuing the goal of understanding in deeper details cellular processes such as growth, metabolic activity, survival and pH0. RESULTS: Results showed that CaCo-2 cells growth and mortality increase after two days in culture when cells were suspended in 3.5 ml volume to respect of 10 ml volume. Different temperature values influenced CaCo-2 cells growth and metabolic activity showing a direct relationship with the volume of the medium. CONCLUSIONS: Our results describe as CaCo-2 cell growth, metabolic activity, mortality and extracellular pH were influenced by extracellular parameters, enabling us to develop and validate a numerical model to be use to predict cells engraftment and proliferation.

Cardiac resynchronization therapy: could a numerical simulator be a useful tool in order to predict the response of the biventricular pacemaker synchronization?

BACKGROUND AND OBJECTIVES: Cardiac resynchronization therapy (CRT) can be considered as an established therapy for patients with moderate or severe heart failure (HF), depressed systolic function and a wide QRS complex. Biventricular stimulation through the CRT is applied at patients with an intra and/or inter-ventricular conduction delay. The goal of this technique is to resynchronize contraction between and within ventricles. A numerical model of the cardiovascular system, together with the numerical model of the biventricular pacemaker (BPM), can be an useful tool to study the better synchronization of the BPM in order to reduce the inter-ventricular and/or intra-ventricular conduction delay. SUBJECTS AND METHODS: Within a group of patients which were representative of the most common disease etiologies of heart failure, seven patients, affected by dilated cardiomyopathy undergoing CRT with BPM, were studied and simulated using the numerical model of the cardiovascular system CARDIOSIM. The patients were submitted to echocardiographic evaluation (with pulsate Doppler and tissue Doppler imaging) and electrocardiography evaluation in order to evaluate intra-ventricular and/or inter-ventricular dyssynchrony. These evaluations were made three times: the first one before BPM implantation, the second and the third one respectively within seven days and six months after BPM implantation. Also haemodynamic parameters were measured. Using the software simulator, the pathological conditions before CRT, within seven days and within six months since CRT were reproduced for each patients in order to evaluate the following haemodynamic parameters: the end-systolic and end-diastolic left ventricular volume, the systolic pulmonary arterial pressure, the systolic, diastolic and mean aortic blood pressure and the ejection fraction. Also the trend of the left ventricular elastance was studied for each patient in order to evaluate the benefits produced by the CRT. RESULTS: The results obtained by means the numerical simulator were in good agreement with clinical data measured on the patients. For each patient also the evolution of the left ventricular elastance was in accordance with the literature data. CONCLUSION: The cardiovascular numerical model seems to be a useful tool to study the synchronization of the BPM in order to reduce the inter-ventricular and/or intra-ventricular conduction delay and to reproduce the condition of a patient.

Application of a user-friendly comprehensive circulatory model for estimation of hemodynamic and ventricular variables.

PURPOSE: Application of a comprehensive, user-friendly, digital computer circulatory model to estimate hemodynamic and ventricular variables. METHODS: The closed-loop lumped parameter circulatory model represents the circulation at the level of large vessels. A variable elastance model reproduces ventricular ejection. The circulatory model has been modified embedding an algorithm able to adjust the model parameters reproducing specific circulatory conditions. The algorithm reads input variables: heart rate, aortic pressure, cardiac output, and left atrial pressure. After a preliminary estimate of circulatory parameters and ventricular elastance, it adjusts the amount of circulating blood, the value of the systemic peripheral resistance, left ventricular elastance, and ventricular rest volume. Input variables and the corresponding calculated variables are recursively compared: the procedure is stopped if the difference between input and calculated variables is within the set tolerance. At the procedure end, the model produces an estimate of ventricular volumes and Emaxl along with systemic and pulmonary pressures (output variables). The procedure has been tested using 4 sets of experimental data including left ventricular assist device assistance. RESULTS: The algorithm allows the reproduction of the circulatory conditions defined by all input variable sets, giving as well an estimate of output variables. CONCLUSIONS: The algorithm permits application of the model in environments where the simplicity of use and velocity of execution are of primary importance. Due to its modular structure, the model can be modified adding new circulatory districts or changing the existing ones. The model could also be applied in educational applications.

Right ventricular assistance by continuous flow device. A numerical simulation.

OBJECTIVES: This work is another step in the development of the circulatory model CARDIOSIM and of its model library. Continuous flow assistance is often used to support the right ventricular failure. Computer simulation is one of the methods to study the effect of this assistance on the failing ventricle. The purpose of this study was to evaluate the effect of this support on some hemodynamic variables, when different right ventricular end-systolic elastance and pump speed values were applied. METHODS: The rotary blood pump model was included into the software package CARDIOSIM, which reproduces the cardiovascular system. Lumped parameters models were used to reproduce the circulatory phenomena. Variable elastance models reproduced the Starling's law of the heart for both ventricles. In the study right ventricular end-systolic elastance (EmaxRIGHT) and the rotational speed of the pump took three different values. All the other parameters of the model were constants. RESULTS: The rotational speed of the pump had a significant influence on right ventricular end-diastolic and end-systolic volumes, right atrial pressure (Pra), right ventricular (Qro) and pump flows. The effects on pulmonary arterial pressure (Pap) were more evident when the right ventricular end-systolic elastance was low. When the speed of the device increased the mean value of Pra decreased for each value of EmaxRIGHT. The total flow (Qro+pump flow) increased when the speed of the pump increased. CONCLUSIONS: Our simulation (in good agreement with the results presented in literature) showed that Hemopump produces a rise in total flow, a drop in blood flow pumped out by the right ventricle and a drop in right atrial pressure.

The impact of rotary blood pump in conjunction with mechanical ventilation on ventricular energetic parameters - numerical simulation.

OBJECTIVES: Aim of this work is to study the impact of left ventricular rotary blood pump assistance, on energetic variables, when mechanical ventilation (MV) of the lungs is applied. METHODS: Computer simulation was used to perform this study. Lumped parameter models reproduce the circulatory system. Variable elastance models reproduce the Starling's law of the heart for each ventricle. After the reproduction of ischemic heart disease left ventricular assistance was applied using a model of rotary blood pump. The pump speed was changed in steps and was assumed to be constant during each step. The influence of mechanical ventilation was introduced by different values of positive mean thoracic pressure. RESULTS: The increase of the rotational speed has a significant influence on some ventricular energetic variables. In fact it decreased left ventricular external work, left and right ventricular pressure-volume area and the left ventricular efficiency. Finally, it increased the right ventricular efficiency but had no influence on the right ventricular external work. The increase of thoracic pressure from -2 to +5 mmHg caused a significant decrease of external work, pressure-volume area (right ventricular pressure-volume area dropped up to 50%) and an increase of right ventricular efficiency (by 40%) while left ventricular efficiency remained almost stable. CONCLUSIONS: Numerical simulation is a very suitable tool to predict changes of not easily measurable parameters such as energetic ventricular variables when mechanical assistance of heart and/or lungs is applied independently or simultaneously.

Modelling in the study of interaction of Hemopump device and artificial ventilation.

The aim of this work is to evaluate in different ventricular conditions the influence of joint mechanical ventilation (MV) and Hemopump assistance. To perform this study, we used a computer simulator of human cardiovascular system where the influence of MV was introduced changing thoracic pressure to positive values. The simulation confirmed that haemodynamic variables are highly sensitive to thoracic pressure changes. On the other hand, Hemopump assistance raises, among the others, mean aortic pressure, total cardiac output (left ventricular output flow plus Hemopump flow) and coronary flow. The simulation showed that the joint action of Hemopump and positive thoracic pressure diminishes these effects.

Development of a hybrid (numerical-hydraulic) circulatory model: prototype testing and its response to IABP assistance.

Merging numerical and physical models of the circulation makes it possible to develop a new class of circulatory models defined as hybrid. This solution reduces the costs, enhances the flexibility and opens the way to many applications ranging from research to education and heart assist devices testing. In the prototype described in this paper, a hydraulic model of systemic arterial tree is connected to a lumped parameters numerical model including pulmonary circulation and the remaining parts of systemic circulation. The hydraulic model consists of a characteristic resistance, of a silicon rubber tube to allow the insertion of an Intra-Aortic Balloon Pump (IABP) and of a lumped parameters compliance. Two electro-hydraulic interfaces, realized by means of gear pumps driven by DC motors, connect the numerical section with both terminals of the hydraulic section. The lumped parameters numerical model and the control system (including analog to digital and digital to analog converters)are developed in LabVIEW environment. The behavior of the model is analyzed by means of the ventricular pressure-volume loops and the time courses of arterial and ventricular pressures and flows in different circulatory conditions. A simulated pathological condition was set to test the IABP and verify the response of the system to this type of mechanical circulatory assistance. The results show that the model can represent hemodynamic relationships in different ventricular and circulatory conditions and is able to react to the IABP assistance.

In vivo and simulation study of artificial ventilation effects on energetic variables in cardiosurgical patients.

OBJECTIVES: The analysis of energetic ventricular variable changes during artificial ventilation, obtained by numerical simulation was done. Twenty-one sets of hemodynamic parameters for eight cardiosurgical patients were used to estimate left and right stroke work. The data were collected for three methods of ventilation: conventional, lung-protective (with minute ventilation diminished by half) and high frequency ventilation (with frequency 5, 10, or 15 Hz). METHODS: The computer simulator (CARDIOSIM) of the cardiovascular system, was used as a tool to calculate values of energetic ventricular variables for conditions that corresponded to these during in vivo measurements. Different methods of ventilation caused differences of intrathoracic pressure, haemodynamic and finally energetic ventricular variables. The trends of these variable changes were the same in in vivo and simulation studies, in the whole range of intrathoracic pressure changes (Pt = 1.5-3.5 mmHg). RESULTS: As values of main hemodynamic variables like cardiac output or arterial, systemic and pulmonary pressures were very close in both studies. Cardiac index and left ventricular stroke work also differed less than 10% for all examined patients and computer simulation. In a case of right ventricular stroke work the difference between in vivo data and simulation was a bit greater than 10% for two of eight patients under study. CONCLUSIONS: Our comparative analysis proved that numerical simulation is a very useful tool to predict changes of main hemodynamic and energy-related ventricular variables caused by different levels of positive Pt. It means that it can help an anesthesiologist to choose an appropriate method of artificial ventilation for cardiosurgical patients.

A simple method for E(max) evaluation: in vitro results.

E(max) is an important parameter to evaluate the state of the heart and of its contractile capability. Its determination is not easy and rather inaccurate: However, it can be clinically relevant during mechanical and/or pharmacological heart assistance as it can suggest how to modify pharmacological therapy or the control strategy of the device. Aim of this study is to develop a method based on ventricular energetics to evaluate E(max). If arterial elastance line slope is modified, for example by a slight peripheral resistance increase, E(max) (assuming that it is constant) can be evaluated computing the energy transferred to the arterial elastance before and after the change. The corresponding equation contains known or easily computable variables and the difference delta between end diastolic volume and ventricular rest volume. If the ratio of deltas before and after the disturbance is near to 1, the equation returns a fair estimation of E(max). The method was tested in vitro, in different circulatory conditions, using an open loop numerical model of the circulation built out of a variable elastance model of the ventricle connected to a modified windkessel representing the systemic arterial tree. The results obtained in in vitro experiments suggest clinically testing this method.

A hybrid mock circulatory system: development and testing of an electro-hydraulic impedance simulator.

Mock circulatory systems are used to test mechanical assist devices and for training and research purposes; when compared to numerical models, however, they are not flexible enough and rather expensive. The concept of merging numerical and physical models, resulting in a hybrid one, is applied here to represent the input impedance of the systemic arterial tree, by a conventional windkessel model built out of an electro-hydraulic (E-H) impedance simulator added to a hydraulic section. This model is inserted into an open loop circuit, completed by another hybrid model representing the ventricular function. The E-H impedance simulator is essentially an electrically controlled flow source (a gear pump). Referring to the windkessel model, it is used to simulate the peripheral resistance and the hydraulic compliance, creating the desired input impedance. The data reported describe the characterisation of the E-H impedance simulator and demonstrate its behaviour when it is connected to a hybrid ventricular model. Experiments were performed under different hemodynamic conditions, including the presence of a left ventricular assist device (LVAD).

Modelling of cardiovascular system: development of a hybrid (numerical-physical) model.

Physical models of the circulation are used for research, training and for testing of implantable active and passive circulatory prosthetic and assistance devices. However, in comparison with numerical models, they are rigid and expensive. To overcome these limitations, we have developed a model of the circulation based on the merging of a lumped parameter physical model into a numerical one (producing therefore a hybrid). The physical model is limited to the barest essentials and, in this application, developed to test the principle, it is a windkessel representing the systemic arterial tree. The lumped parameters numerical model was developed in LabVIEW environment and represents pulmonary and systemic circulation (except the systemic arterial tree). Based on the equivalence between hydraulic and electrical circuits, this prototype was developed connecting the numerical model to an electrical circuit--the physical model. This specific solution is valid mainly educationally but permits the development of software and the verification of preliminary results without using cumbersome hydraulic circuits. The interfaces between numerical and electrical circuits are set up by a voltage controlled current generator and a voltage controlled voltage generator. The behavior of the model is analyzed based on the ventricular pressure-volume loops and on the time course of arterial and ventricular pressures and flow in different circulatory conditions. The model can represent hemodynamic relationships in different ventricular and circulatory conditions.

Energetic parameter changes with mechanical ventilation in conjunction with BVAD assistance.

The aim was to assess the influence of a biventricular assist device (BVAD) on ventricular energetics parameters (external work, oxygen consumption, cardiac mechanical efficiency) for both ventricles, when mechanical ventilation was applied. The experiments were performed using a computer simulator of cardiovascular system (CARDIOSIM) after modelling a pathological state of the left ventricle (E(v)Left = 0. 9 mmHg cm(-3) and increasing pulmonary resistance (Rap = 0.3 mmHg cm(-3 s). The effect of mechanical ventilation was mean intrathoracic pressure changes from 0 to +5 mmHg. This simulation showed that application of BVAD for both ventricles reduces external work and that this effect is stressed by positive intrathoracic pressure, reduces cardiac mechanical efficiency that is quite insensitive to intrathoracic pressure and increases oxygen consumption, which is reduced by positive intrathoracic pressure. The increase of potential energy at the onset of BVAD evidences a rightwards shift of ventricular work cycle (unloading of the ventricles). In general, positive intrathoracic pressure during BVAD assistance adversely affects ventricular energetics.

Study of systolic pressure variation (SPV) in presence of mechanical ventilation.

Systolic pressure variation (SPV) and its components (dUp and dDown) have been demonstrated to be of interest in assessing preload in mechanically ventilated patients. The aim of this paper is to analyse the sensitivity of these variables to preload and volemic changes during mechanical ventilation in different conditions of the cardiovascular system. Computer simulation experiments have been done using a modular lumped parameter model of the cardiovascular system. The effect of mechanical ventilation has been reproduced operating on intrathoracic pressure. Experiments have been performed varying preload through filling pressure. Sensitivity of SVP dUp and dDown is described varying separately left ventricular elastance (Ev), systemic arterial resistance (Ras) and systemic arterial compliance (Cas). The sensitivity of SPV and dDown to preload and filling pressure is appreciable for high values of Ev and for a wide variation of Ras. Preliminary clinical data concerning the three parameters show good correlation with simulation results.

Ventricular energetics during mechanical ventilation and intraaortic balloon pumping--computer simulation.

Computer simulation of a cardiovascular system enabled us to predict the effects of simultaneous application of mechanical ventilation (MV) and intraaortic ballon pumping (IABP) on ventricular energetics. External work (EW), pressure-volume area (PVA), potential energy (PE) and cardiac mechanical efficiency (CME) were calculated. Nummerical simulation showed that changes of positive intrathoracic pressure have a considerable effect on left and right ventricular EW, PE, PVA and CME, whether IABP is used or not. The right ventricular energetics was much less influenced by systemic resistance (Ras) changes than the left ventricular one. Simultaneous application of IABP and MV showed a remarkable effect on left ventricular EW. The net result was reversed sensitivity to pulmonary resistance (Rap) and reduced sensitivity to Ras. PVA was generally reduced, while CME is increased by simultaneous presence of IABP and MV. The sensitivity of CME to Rap and Ras variation was diminished in this situation.

Mono and bi-ventricular assistance: their effect on ventricular energetics.

When mono- and bi-ventricular mechanical assistance is used for heart recovery, its control strategy and circulatory variables affect ventricular energetics (external work-EW, oxygen consumption-VO2, cardiac mechanical efficiency-CME). This study is based on the data obtained in vitro and presents an analysis of the effects of the mono- and bi-ventricular mechanical assistance on ventricular energetics. The assistance was conducted on the principle of counterpulsation with atrio-arterial connection. It includes the following stages: 1) the characterisation of the isolated ventricle model in terms of EW, VO2 and CME as a function of the filling pressure and peripheral resistance, 2) modelling of left ventricular and pulmonary dysfunction, followed by left ventricular and bi-ventricular assistance. Experimental data enable us to draw the following conclusions: * in general, the greatest hemodynamic improvement does not correspond to the highest energetic improvement, * LVAD assistance deteriorates left ventricular CME while its effect on right ventricular energetics depends on the value of right ventricular elastance (Emax). Right ventricular CME is deteriorated by BVAD assistance irrespective of right Emax, * the energetics optimisation in bi-ventricular assistance is closely related to the right Emax, which could probably be a deciding factor in the choice of the assistance mode.

A hybrid (numerical-physical) model of the left ventricle.

Hydraulic models of the circulation are used to test mechanical devices and for training and research purposes; when compared to numerical models, however, they are not flexible enough and rather expensive. The solution proposed here is to merge the characteristics and the flexibility of numerical models with the functions of physical models. The result is a hybrid model with numerical and physical sections connected by an electro-hydraulic interface - which is to some extent the main problem since the numerical model can be easily changed or modified. The concept of hybrid model is applied to the representation of ventricular function by a variable elastance numerical model. This prototype is an open loop circuit and the physical section is built out of a reservoir (atrium) and a modified windkessel (arterial tree). The corresponding equations are solved numerically using the variables (atrial and arterial pressures) coming from the physical circuit. Ventricular output flow is the computed variable and is sent to a servo amplifier connected to a DC motor-gear pump system. The gear pump, behaving roughly as a flow source, is the interface to the physical circuit. Results obtained under different hemodynamic conditions demonstrate the behaviour of the ventricular model on the pressure-volume plane and the time course of output flow and arterial pressure.

IABP assistance: a test bench for the analysis of its effects on ventricular energetics and hemodynamics.

IABP assistance is frequently used to support heart recovery, improving coronary circulation and re-establishing the balance between oxygen availability and consumption. Hemodynamic and energetic parameters (endocardial viability ratio, ventricular energetics) are used to evaluate its effectiveness which depends on internal (timing, balloon volume and position) and external factors (circulatory conditions). Considering short, medium and long-term effects of IABP, the first depends on its mechanical action, the latter on the changes induced in circulatory parameters. The analysis of the first is important because conditions for the onset of a virtuous cycle able to support ventricular recovery are created. Simulation systems could be helpful in this analysis for the implicit reliability and reproducibility of the experiments, provided that they are able to reproduce both hemodynamic phenomena and energetic relationships. The aim of this paper is to present a system originally developed to test mechanical heart assist devices and modified for IABP testing. Data reported here are obtained from in vitro experiments. A partial verification, obtained from the literature is presented.