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Biomedical subjects

D Jaron

Publications and source records attributed to D Jaron.

At least 19 recordsLinked to original sources

Heterogeneous response of microvascular endothelial cells to shear stress.

We investigated changes in calcium concentration in cultured bovine aortic endothelial cells (BAECs) and rat adrenomedulary endothelial cells (RAMECs, microvascular) in response to different levels of shear stress. In BAECs, the onset of shear stress elicited a transient increase in intracellular calcium concentration that was spatially uniform, synchronous, and dose dependent. In contrast, the response of RAMECs was heterogeneous in time and space. Shear stress induced calcium waves that originated from one or several cells and propagated to neighboring cells. The number and size of the responding groups of cells did not depend on the magnitude of shear stress or the magnitude of the calcium change in the responding cells. The initiation and the propagation of calcium waves in RAMECs were significantly suppressed under conditions in which either purinergic receptors were blocked by suramin or extracellular ATP was degraded by apyrase. Exogenously applied ATP produced similarly heterogeneous responses. The number of responding cells was dependent on ATP concentration, but the magnitude of the calcium change was not. Our data suggest that shear stress stimulates RAMECs to release ATP, causing the increase in intracellular calcium concentration via purinergic receptors in cells that are heterogeneously sensitive to ATP. The propagation of the calcium signal is also mediated by ATP, and the spatial pattern suggests a locally elevated ATP concentration in the vicinity of the initially responding cells.

Adenosine Triphosphate↗

Incorporating O2-Hb reaction kinetics and the Fåhraeus effect into a microcirculatory O2-CO2 transport model.

The influence of O2-Hb reaction kinetics and the Fåhraeus effect on steady state O2 and CO2 transport in cat brain microcirculation was investigated using our refined multicompartmental model. The most important model predictions include: 1) capillaries are the sites in the microcirculation where the effect of O2-Hb kinetics is most pronounced; 2) while there is only a small difference between equilibrium and actual oxygen saturation, this effect is not negligible; 3) O2-Hb kinetics tends to make the PO2 level at the venous entrance higher than in venules; 4) the influence of the Fåhraeus effect leads to a lower tissue PO2 level than in venules and the outlet vein. The resultant decline in tissue PO2 may lead to a decrease in O2 consumption rate and extraction ratio; 5) although the Fåhraeus effect changes the ratio between arteriolar flux and capillary flux, incorporating the Fåhraeus effect and O2-Hb kinetics into the simulation does not change our previous conclusion, that most of the O2 and CO2 exchange takes place at the capillary level; 6) in general, influences of O2-Hb kinetics and Fåhraeus effect are synergistic; 7) a model that excludes these two mechanisms might overestimate the tissue oxygenation level especially during severe hypoxia.

Algorithms↗

Arteriolar contribution to microcirculatory CO2/O2 exchange.

The role of arterioles and capillaries in microcirculatory gas exchange was evaluated using a multicompartmental model for O2-CO2 transport in the rat skeletal microcirculation. Model predictions were examined to investigate the effects of model formulation and model parameter values. The factors in model formulation included radial blood diffusion resistance, the discrete nature of capillary blood, and the method of determining compartmental fluxes. A comparison with earlier models in the literature indicated that, by refining the method for determining compartmental fluxes, the CO2 flux contribution ratio of arterioles versus capillaries (Fa/Fc) increased by 52% during rest and diminished by 34% during moderate exercise. It also resulted in negative venular fluxes during exercise. Incorporating radial blood diffusion resistance into the model lead to a decrease of up to 43% in Fa/Fc. It also resulted in a decrease in central arteriole-venule shunt. Including the discrete nature of capillary blood into the model caused a small increase in Fa/Fc. Results indicated similar effects of these factors on oxygen Fa/Fc. Model parameters whose effects were investigated included metabolic rate (M), blood flow rate (Q), ratio of arteriolar diffusion conductance versus capillary diffusion conductance (Ea/Ec), the magnitude of arteriolar diffusion conductances (Ea), and the CO2/O2 respiratory quotient (Qu). Simulation results suggested that Q was a major factor responsible for the variations in Fa/Fc when the rest/exercise state of rat skeletal muscle changes. Ea and Qu were also responsible for differences in model predictions for different body organs or animal species. Our model predicts capillary dominance in both CO2 and O2 exchange and reveals the existence, under certain conditions, of negative venular flux contribution.

Algorithms↗

Autoregulation in the stenosed coronary circulation.

Coronary vessel stenosis increases vascular resistance and limits the dynamic range of autoregulation. In this study, the limitation imposed by stenosed vessels on oxygen delivery to the myocardium was investigated using a theoretical model. For different degrees of stenosis and for different levels of arteriovenous oxygen content difference, the model predicted the limits of the contractility range for which ventricular oxygen balance is positive. The model also predicted the existence of an optimal contractility level which minimizes the cost of arterial pressure generation and provides the largest coronary oxygen reserve. With severe stenosis, myocardial oxygen balance is extremely sensitive to changes in the level of stenosis. The range of contractility in which the coronary circulation can meet the myocardial oxygen needs is dramatically reduced by small increases in stenosis severity or small decreases in arteriovenous oxygen difference. When the optimal contractility level is maintained, the heart can tolerate these detrimental changes to a greater extent.

Animals↗

Contributions of oxygen dissociation and convection to the behavior of a compartmental oxygen transport model.

We previously derived a compartmental model for oxygen transport in vascular blood in which lumped terms, representing convective and oxygen dissociative effects, were obtained from a distributed model by space averaging. In this paper, we compare the results of this model and those of another compartmental model from the literature in which these terms were selected arbitrarily. The use of space-averaged parameters resulted in a more distinct difference in calculated partial pressures of oxygen between capillary and venule compartments, more accurate distribution patterns for partial pressures of oxygen through the venule compartments, and a capability to simulate conditions under which mean oxygen partial pressure in tissue is higher than in the venules. These results are supported by available experimental findings. Results also showed that the employment of space-averaged convective terms had a greater effect on the distribution of compartmental partial pressures than did the use of the cross-sectional averaged oxygen-hemoglobin binding function. The latter produced significant changes only for certain compartments, and only under extreme physiologic conditions. The results demonstrate our model's ability to reflect relationships among capillary, venule, and tissue compartmental partial pressures under varying conditions.

Algorithms↗

A mathematical model of G time-tolerance.

We propose a model to explain experimentally observed effects of Gz onset rates and levels on the time of occurrence of loss of vision and/or consciousness. The model is based on the existence of two generally accepted parameters: a G limit beyond which cerebral perfusion ceases, and a buffer time between loss of perfusion and loss of function. When applied to ramp onset G profiles, the model predicts a generally hyperbolic locus of endpoints, similar to the well-known Stoll curve, except for the dip. The advantage of the model is its applicability to any G onset profile. Data from the literature support the assumptions of the model and its results, including the absence of the dip in the locus for a ramp onset. The results call into question some concepts used to design G avoidance inflight strategies and the usefulness of some experimental centrifuge methods. The model may enable an increase in the accuracy of predictions of the time of visual or cerebral loss of function under various G profiles.

Adaptation, Physiological↗

Cardiovascular responses to external counterpulsation: a computer simulation.

A mathematical model of the human cardiovascular system is presented which includes a simulation of cardiac assistance by external counterpulsation. The model was established to study the effects of external counterpulsation on cardiovascular haemodynamics. The closed simulation includes both the left and the right heart and the pulmonary circulation. The model is able to provide data for the behaviour of the system under varying modes of assistance. Our results suggest that control of external counterpulsation is more difficult than control of the intra-aortic balloon pump and requires regulation of a larger number of variables. The results also suggest that a tradeoff exists between improved oxygen delivery to the heart and reduction in the oxygen consumption of the myocardium, an observation similar to that reported for the intra-aortic balloon pump.

Counterpulsation↗

Optimal controller for intraaortic balloon pumping.

An optimal control algorithm was adapted to identify and track the optimal deflation time of the intraaortic balloon pump (IABP). Routines for handling physiologically imposed constraints were added to the algorithm which was implemented in a computer-controlled system. The system was designed to provide real time optimization for the clinical setting. The controller continuously maximizes a performance index while observing the constraints. The index is composed of clinically available hemodynamic variables which indicate changes in myocardial energy balance. Proper values for the algorithm parameters were determined and the system was tested in animal experiments. The results indicate that controlling deflation time relative to the R wave, which precedes the next ejection phase, reduces the time required for optimization when the heart rate varies.

Algorithms↗

Optimal control system for the intra-aortic balloon pump.

An optimal control system for the intra-aortic balloon pump (IABP) is presented. Control of the IABP is based on a performance index formulated to reflect a tradeoff between maximising cardiac oxygen supply and minimising cardiac oxygen consumption. In the performance index, mean diastolic pressure (MDP) was used to represent oxygen availability and peak systolic pressure (PSP) was used to represent oxygen consumption. An algorithm, implemented using an 8-bit microcomputer, changes the deflation time of the IABP to maximise this performance index by using an optimisation technique that employs both a search and an approximation. The search produces three equally spaced points which define a region that includes the maximum of the performance index. From these points, the optimum deflation time is estimated by a quadratic approximation. The algorithm has been successfully tested using performance index curves generated by computer simulations.

Algorithms↗

Computer simulation of the mechanically-assisted failing canine circulation.

A model of the cardiovascular system is presented. The model includes representations of the left and right ventricles, a nonlinear multielement model of the aorta and its main branches, and lumped models of the systemic veins and the pulmonary circulation. A simulation of the intra-aortic balloon pump and representations of physiological compensatory mechanisms are also incorporated in the model. Parameters of the left ventricular model were set to simulate either the normal or failing canine circulation. Pressure and flow waveforms throughout the circulation as well as ventricular pressure and volume were calculated for the normal, failing, and assisted failing circulation. Cardiac oxygen supply and consumption were calculated from the model. They were used as direct indices of cardiac energy supply and utilization to assess the effects of cardiac assistance.

Animals↗

Cardiac energy considerations during intraaortic balloon pumping.

Cardiac oxygen availability and oxygen consumption were used in a theoretical study as indexes of myocardial energy supply and utilization, respectively. A detailed computer simulation of the closed-loop canine cardiovascular system was utilized to study the dependence of these indexes on timing of the intraaortic balloon pump. Oxygen availability exhibited higher sensitivity to balloon timing than oxygen utilization. While maximum augmentation of oxygen availability was 58 percent, oxygen consumption could be reduced by only 13 percent. Animal experiments were initiated to validate the theoretical results. The results of both the animal experiments and the computer simulation suggested that neither balloon timing which maximizes oxygen availability nor timing which minimizes oxygen consumption correlates with timing which minimizes aortic end diastolic pressure. Thus, end diastolic pressure, presently used as a determinant of proper timing in patients undergoing cardiac assistance, was found to be a poor index of ventricular energy consumption. A performance index comprised of clinically available variables, was formulated to reflect myocardial energy balance. In this performance index, mean diastolic pressure was used to represent energy availability and peak systolic pressure was used as an index of oxygen consumption. Their relationship to oxygen balance and their dependence on timing were studied using the computer simulation of the canine cardiovascular system and animal experiments. Theoretical and experimental results suggest that such an index is capable of representing O2 balance and can be used to control phasing of the device.

Animals↗

Reflectance photoplethysmography as an adjunct to assessment of gravitational acceleration tolerance: preliminary findings.

We have examined the feasibility of using reflectance photoplethysmography to assess Gz acceleration tolerance. Reflectance plethysmograms recorded using a sensor placed on the region of the superficial temporal artery were analysed along with the mean value and the pulsatile component of the Doppler velocity recorded from the opposite temporal artery. The photoplethysmogram signal and pulsatile and mean Doppler velocities were examined as predictors of impending peripheral light loss (PLL) during the experiments. Photoplethysmography correctly predicted a large percentage of the PLL runs (80.5%) and non-PLL runs (98.3%). Mean Doppler velocity predicted a higher percentage of PLL runs (88.1%), but with an unacceptably low rate of non-PLL runs (77.2%). The pulsatile Doppler velocity yielded only 50.7% correct prediction of PLL runs. The results of this preliminary study indicate that, with an improved design of the sensor and the electronics, it may be possible to use reflectance photoplethysmography in acceleration tolerance experiments as a reliable predictor of impending peripheral light loss.

Acceleration↗

An experimental microcomputer controlled system for synchronized pulsating anti-gravity suit.

An experimental system to deliver synchronized external pressure pulsations to the lower body is described in this technical note. The system is designed using a microcomputer with a real time interface and an electro-pneumatic subsystem capable of delivering pressure pulses to a modified anti-G suit at a fast rate. It is versatile, containing many options for synchronizing, phasing and sequencing of the pressure pulsations and controlling the pressure level in the suit bladders. Details of its software and hardware are described along with the results of initial testing in a Dynamic Flight Simulator on human volunteers.

Computers↗