Dov Jaron - Academia.edu (original) (raw)

Papers by Dov Jaron

PubMed, Jun 1, 1987

We have examined the feasibility of using reflectance photoplethysmography to assess Gz accelerat... more 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.

PubMed, Oct 1, 1993

We propose a model to explain experimentally observed effects of Gz onset rates and levels on the... more 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.

Nitric Oxide, Jun 1, 2021

Endothelial dysfunction, characterised by impaired nitric oxide (NO) bioavailability, arises in r... more Endothelial dysfunction, characterised by impaired nitric oxide (NO) bioavailability, arises in response to a variety of cardiovascular risk factors and precedes atherosclerosis. NO is produced by tight regulation of endothelial nitric oxide synthase (eNOS) activity in response to vasodilatory stimuli. This regulation of eNOS is mediated in part by store-operated calcium entry (SOCE). We hypothesised that both ATP- and flow-induced eNOS activation are regulated by SOCE derived from Orai1 channels and members of the transient receptor potential canonical (TRPC) channel family. Bovine aortic endothelial cells (BAECs) were pre-treated with pharmacological inhibitors of TRPC channels and Orai1 to examine their effect on calcium signaling and eNOS activation in response to flow and ATP. The peak and sustained ATP-induced calcium signal and the resulting eNOS activation were attenuated by inhibition of TRPC3, which we found to be store operated. TRPC4 blockade reduced the transient peak in calcium concentration following ATP stimulation, but did not significantly reduce eNOS activity. Simultaneous TRPC3 & 4 inhibition reduced flow-induced NO production via alterations in phosphorylation-mediated eNOS activity. Inhibition of TRPC1/6 or Orai1 failed to lower ATP-induced calcium entry or eNOS activation. Our results suggest that TRPC3 is a store-operated channel in BAECs and is the key regulator of ATP-induced eNOS activation, whereas flow stimulation also recruits TRPC4 into the pathway for the synthesis of NO.

A partial pressure dependent metabolic mechanism was incorporated into our previous multicompartm... more A partial pressure dependent metabolic mechanism was incorporated into our previous multicompartmental model for O2-CO2 coupled transport in the cat cerebral microcirculation-tissue system. The refined model predicts the distribution of O2 and CO2 concentrations and regional flux along the microcirculation under various hemodynamic and metabolic conditions. Our simulation indicates that capillaries are the main site for O2 as well as

The authors derive a compartmental model for oxygen transport in vascular blood which is suitable... more The authors derive a compartmental model for oxygen transport in vascular blood which is suitable for both steady and time-varying analysis, and which can be used with any kind of oxygen dissociation function. The derivation focuses on the establishment of expressions for the lumped convective term and the lumped oxygen dissociation function. Results of the simulation show that the value

Microcirculation, Jul 10, 2018

Objectives: The effect of nitric oxide (NO) on smooth muscle cell contractility is crucial in reg... more Objectives: The effect of nitric oxide (NO) on smooth muscle cell contractility is crucial in regulating vascular tone, blood flow, and O 2 delivery. Quantitative predictions for interactions between the NO production rate and the myogenic response for microcirculatory blood vessels are lacking.

IEEE Engineering in Medicine and Biology Magazine, Mar 1, 1991

A model of the cardiovascular system developed for use in the study of cardiovascular responses t... more A model of the cardiovascular system developed for use in the study of cardiovascular responses to acceleration of the type encountered by pilots of high-performance aircraft is described. The model includes simulations of the heart; arterial, venous, and peripheral circulations; and physiological compensatory mechanisms important to acceleration studies. It can predict blood pressure and flow in any part of the circulation under conditions of G(z) stress and with the application of G-protection techniques. Predictions of the model have been used to analyze the cause of loss of pilot function under G forces, and to design an improved anti-G suit.

Proceedings of the Annual International Conference of the IEEE Engineering in Medicine and Biology Society, 1988

A description is given of the development of a novel mode of acceleration protection for pilots o... more A description is given of the development of a novel mode of acceleration protection for pilots of high-performance aircraft. Design of the protection system was done in iterative cycles of mathematical modeling, hardware and software design, and experimental testing. The model was used both as a means of quantitatively investigating acceleration effects and as a tool for studying the relative

Microvascular Research, Jul 1, 1993

Annals of Biomedical Engineering, Mar 1, 1985

The effectiveness of intraaortic balloon pumping was investigated by using a lumped parameter mod... more The effectiveness of intraaortic balloon pumping was investigated by using a lumped parameter model of the cardiovascular/assist device system. The model consists of a time-varying elastance left ventricular simulation, a 2-element windkessel arterial simulation, and an RC venous return and pulmonary simulation. The four major hemodynamic variables, stroke volume (SV), aortic mean diastolic pressure (MDP), tension time index (TTI), and aortic end diastolic pressure (EDP), were divided into two categories related to system energy supply and demand: "external" and "'internal" variables. The effects of balloon pumping on these variables can be described by closed-form equations that yield an optimal solution. The model prediction suggests that, in the ideal case, optimization of balloon pumping calls for instantaneous inflation of the balloon to maximum volume at end systole and instantaneous complete deflation at end diastole. For finite inflation/deflation rates, the optimal time for the start of inflation is end systole. Deflation timing, however, involves a tradeoff between maximizing the external variables and minimizing the internal variables. These predictions were tested using a nonlinear digital computer model. The results also suggest that when SV is not being monitored, optimal inflation timing can be controlled from the measurements of TTI or pulmonary venous pressure; optimal deflation timing can be controlled by a weighted combination of MDP and EDP.

When myocardial infarction compromises cardiac output, treatment sometimes involves the applicati... more When myocardial infarction compromises cardiac output, treatment sometimes involves the application of a pulsatile synchronous left ventricular assist device (LVAD). The authors use a computer simulation to explore the possibility of optimal phasing of pump cycle with respect to events in the cardiac cycle from the standpoint of improved myocardial energetics and system flow. Central to the simulation is a

Cellular and Molecular Bioengineering, Mar 19, 2018

Colocalization of endothelial nitric oxide synthase (eNOS) and capacitative Ca2+ entry (CCE) chan... more Colocalization of endothelial nitric oxide synthase (eNOS) and capacitative Ca2+ entry (CCE) channels in microdomains such as cavaeolae in endothelial cells (ECs) has been shown to significantly affect intracellular Ca2+ dynamics and NO production, but the effect has not been well quantified. We developed a two-dimensional continuum model of an EC integrating shear stress-mediated ATP production, intracellular Ca2+ mobilization, and eNOS activation to investigate the effects of spatial colocalization of plasma membrane eNOS and CCE channels on Ca2+ dynamics and NO production in response to flow-induced shear stress. Our model examines the hypothesis that subcellular colocalization of cellular components can be critical for optimal coupling of NO production to blood flow. Our simulations predict that heterogeneity of CCE can result in formation of microdomains with significantly higher Ca2+ compared to the average cytosolic Ca2+. Ca2+ buffers with lower or no mobility further enhanced Ca2+ gradients relative to mobile buffers. Colocalization of eNOS to CCE channels significantly increased NO production. Our results provide quantitative understanding for the role of spatial heterogeneity and the compartmentalization of signals in regulation of shear stress-induced NO production.

ABSTRACT In order to understand changes in the ventilation/perfusion ratio encountered by pilots ... more ABSTRACT In order to understand changes in the ventilation/perfusion ratio encountered by pilots of high performance aircraft, we developed an n-zone hemodynamic model of the pulmonary circulation to be associated with a compartmental model of the respiratory system. The results of our studies are intended to improve our understanding of pilots' tolerance to sustained high acceleration stress.

Cellular Signalling, Nov 1, 2021

BACKGROUND Protein Kinase C (PKC) is a promiscuous serine/threonine kinase regulating vasodilator... more BACKGROUND Protein Kinase C (PKC) is a promiscuous serine/threonine kinase regulating vasodilatory responses in vascular endothelial cells. Calcium-dependent PKCbeta (PKCβ) and calcium-independent PKCeta (PKCη) have both been implicated in the regulation and dysfunction of endothelial responses to shear stress and agonists. OBJECTIVE We hypothesized that PKCβ and PKCη differentially modulate shear stress-induced nitric oxide (NO) production by regulating the transduced calcium signals and the resultant eNOS activation. As such, this study sought to characterise the contribution of PKCη and PKCβ in regulating calcium signaling and endothelial nitric oxide synthase (eNOS) activation after exposure of endothelial cells to ATP or shear stress. METHODS Bovine aortic endothelial cells were stimulated in vitro under pharmacological inhibition of PKCβ with LY333531 or PKCη targeting with a pseudosubstrate inhibitor. The participation of PKC isozymes in calcium flux, eNOS phosphorylation and NO production was assessed following stimulation with ATP or shear stress. RESULTS PKCη proved to be a robust regulator of agonist- and shear stress-induced eNOS activation, modulating calcium fluxes and tuning eNOS activity by multi-site phosphorylation. PKCβ showed modest influence in this pathway, promoting eNOS activation basally and in response to shear stress. Both PKC isozymes contributed to the constitutive and induced phosphorylation of eNOS. The observed PKC signaling architecture is intricate, recruiting Src to mediate a portion of PKCη's control on calcium entry and eNOS phosphorylation. Elucidation of the importance of PKCη in this pathway was tempered by evidence of a single stimulus producing concurrent phosphorylation at ser1179 and thr497 which are antagonistic to eNOS activity. CONCLUSIONS We have, for the first time, shown in a single species in vitro that shear stress- and ATP-stimulated NO production are differentially regulated by classical and novel PKCs. This study furthers our understanding of the PKC isozyme interplay that optimizes NO production. These considerations will inform the ongoing design of drugs for the treatment of PKC-sensitive cardiovascular pathologies.

REPORT NUMBERING SYSTEM-The numbering of technical project reports issued by the Naval Air Develo... more REPORT NUMBERING SYSTEM-The numbering of technical project reports issued by the Naval Air Development Center is arranged for specific identification purposes. Each number consists of the Center acronym, the calendar year in which the number was assigned, the sequence number of the report within the specific calendar year, and the official 2-digit correspondence code of the Command Office or the Functional Directorate responsible for the report. For example, Report No. NADC-86015-20 indicates the fifteenth Center report for the year 1986, and prepared by the Systems Directorate. The numerical codes are as follows: CODE OFFICE OR DIRECTORATE 00 Commander, Naval Air Development Center 01 Technical Director, Naval Air Development Center 02 Comptroller * 10 Directorate Command Projects 20 Systems Directorate 30 Sensors & Avionics Technology Directorate 40 Communications and Navigation Technology Directorate 50 Software Computer Directorate 60 Aircraft & Crew Systems Technology Directorate 70 Planning Assessment Resources 80 Engineering Support Group PRODUCT ENDORSEMENT-The discussion or instructions concerning commercial products herein do not constitute an endorsement by the Government nor do they convey or imply the license or right to use such products.

A transmission line model is used to estimate the pressure waveform from flow measurements at thr... more A transmission line model is used to estimate the pressure waveform from flow measurements at three sites of an excised canine carotid artery. The resulting waveform shows good correlation with the actual pressure measured using a pressure transducer inserted into the artery. An example is given, showing the comparison of the pressure waveforms calculated from the model and those measured

Annals of Biomedical Engineering, Mar 1, 1993

A popular and useful technique used to model blood flow in cardiovascular simulations is to divid... more A popular and useful technique used to model blood flow in cardiovascular simulations is to divide each blood vessel into a series of segments, each with its own lumped resistance, inertance, and compliance parameters. The values of these parameters are usually obtained through a simplification of the Navier-Stokes equations for fluid flow. However, the simplification often ignores the nonlinear and convective terms of the equations, resulting in errors in the parameter values, especially in the value found for resistance per unit length. We report a new method for the calculation of vessel resistance per unit length which takes into account the effects of vessel taper and wall compliance. It is shown that these effects can be addressed by the addition of two time-varying terms to the calculation of resistance per unit length. One term, due to vessel taper, is proportional to volumetric flow rate Q. The other term, due to vessel compliance, is proportional to Op/Ot. These variables are readily available in computer simulations of blood flow in lumped parameter systems. Using data for the descending aorta, the new parameter values, when averaged over a cardiac cycle, compare favorably with results in the literature.

Advances in Experimental Medicine and Biology, 2011

Recent evidence in the literature suggests that tissues play a greater role than blood in reducin... more Recent evidence in the literature suggests that tissues play a greater role than blood in reducing nitrite to NO under ischemic or hypoxic conditions. Our previous mathematical model for coupled NO and O(2) transport around an arteriole, modified to include superoxide generation from dysfunctional endothelium, was developed further to include nitrite reductase activity in blood and tissue. Steady-state radial and axial NO and pO(2) profiles in the arteriole and surrounding tissue were simulated for different blood flow rates and arterial blood pO(2) values. The resulting computer simulations demonstrate that nitrite reductase activity in blood is not a very effective mechanism for conserving NO due to the strong scavenging of NO by hemoglobin. In contrast, nitrite reductase activity in tissue is much more effective in increasing NO bioavailability in the vascular wall and contributes progressively more NO as tissue hypoxia becomes more severe.