Non-invasive assessment of stroke volume and cardiovascular parameters based on peripheral pressure waveform.

Cardiovascular diseases are the leading cause of death globally, making the development of non-invasive and simple-to-use tools that bring insights into the state of the cardiovascular system of utmost importance. We investigated the possibility of using peripheral pulse wave recordings to estimate stroke volume (SV) and subject-specific parameters describing the selected properties of the cardiovascular system. Peripheral pressure waveforms were recorded in the radial artery using applanation tonometry (SphygmoCor) in 35 hemodialysis (HD) patients and 14 healthy subjects. The pressure waveforms were then used to estimate subject-specific parameters of a mathematical model of pulse wave propagation coupled with the elastance-based model of the left ventricle. Bioimpedance cardiography measurements (PhysioFlow) were performed to validate the model-estimated SV. Mean absolute percentage error between the simulated and measured pressure waveforms was 4.0% and 2.8% for the HD and control group, respectively. We obtained a moderate correlation between the model-estimated and bioimpedance-based SV (r = 0.57, p<0.05, and r = 0.58, p<0.001, for the control group and HD patients, respectively). We also observed a correlation between the estimated end-systolic elastance of the left ventricle and the peripheral systolic pressure in both HD patients (r = 0.84, p<0.001) and the control group (r = 0.70, p<0.01). These preliminary results suggest that, after additional validation and possibly further refinement to increase accuracy, the proposed methodology could support non-invasive assessment of stroke volume and selected heart function parameters and vascular properties. Importantly, the proposed method could be potentially implemented in the existing devices measuring peripheral pressure waveforms.

The Impact of Energy Drink Consumption on Heart Rate Variability after Exercise.

The effects of caffeine or caffeine-based energy drinks on the recovery of autonomic nervous system balance after exercise have been the subject of several studies which yielded inconclusive results. In a recent study by Porto et al., the impact of a caffeine-based energy drink on heart rate variability (HRV) before and after a moderate aerobic exercise (running on a treadmill) has been studied in a randomized, crossover trial on healthy and active young males. It was concluded that an energy drink consumed before exercise did not affect HRV indices during post-exercise recovery. However, this conclusion is somewhat inconsistent with the reported data and hence may be misleading. Here, I discuss the shortcomings of that study and point out some inaccuracies in the reported results. Considering the above, it appears that energy drink consumption may affect some HRV indices after exercise, at least those related to high frequency changes in the autonomic activity.

Vascular refilling coefficient is not a good marker of whole-body capillary hydraulic conductivity in hemodialysis patients: insights from a simulation study.

Refilling of the vascular space through absorption of interstitial fluid by micro vessels is a crucial mechanism for maintaining hemodynamic stability during hemodialysis (HD) and allowing excess fluid to be removed from body tissues. The rate of vascular refilling depends on the imbalance between the Starling forces acting across the capillary walls as well as on their hydraulic conductivity and total surface area. Various approaches have been proposed to assess the vascular refilling process during HD, including the so-called refilling coefficient (Kr) that describes the rate of vascular refilling per changes in plasma oncotic pressure, assuming that other Starling forces and the flow of lymph remain constant during HD. Several studies have shown that Kr decreases exponentially during HD, which was attributed to a dialysis-induced decrease in the whole-body capillary hydraulic conductivity (LpS). Here, we employ a lumped-parameter mathematical model of the cardiovascular system and water and solute transport between the main body fluid compartments to assess the impact of all Starling forces and the flow of lymph on vascular refilling during HD in order to explain the reasons behind the observed intradialytic decrease in Kr. We simulated several HD sessions in a virtual patient with different blood priming procedures, ultrafiltration rates, session durations, and constant or variable levels of LpS. We show that the intradialytic decrease in Kr is not associated with a possible reduction of LpS but results from the inherent assumption that plasma oncotic pressure is the only variable Starling force during HD, whereas in fact other Starling forces, in particular the oncotic pressure of the interstitial fluid, have an important impact on the transcapillary fluid exchange during HD. We conclude that Kr is not a good marker of LpS and should not be used to guide fluid removal during HD or to assess the fluid status of dialysis patients.

Basic physics of hemodiafiltration.

Standard high-flux hemodialysis (HD) clears urea very efficiently but is less efficient at clearing uremic toxins with larger molecule size, which diffuse more slowly. Hemodiafiltration (HDF) provides much higher convection rates, thereby reliably increasing the clearance of these larger toxins. However, the high ultrafiltration volumes employed by HDF significantly increase the concentration of proteins and lipids in the dialyzer blood compartment. This has the effect of increasing plasma viscosity, which opposes solute diffusion, and increasing plasma oncotic pressure, which opposes convection. The negatively charged plasma proteins also influence the equilibration of ions between dialysate and blood compartments. These effects result in varying conditions for solute transport along the length of the dialyzer and along the radial distance from the membrane within the dialyzer fibers. High-flux dialyzers can be designed to augment solute diffusion and internal filtration, so that their performance approaches that of HDF. This avoids some of the mechanical complexity of HDF, but such enhanced dialyzers may be more difficult to manufacture, control and monitor. Here, we present and discuss the most important physical phenomena associated with HDF therapy, providing an overview of its main concepts and principles. In particular, we discuss the physics of solute diffusion and convection and the factors affecting them, and we compare predilution or postdilution HDF with enhanced HD.

Calculation of the Gibbs-Donnan factors for multi-ion solutions with non-permeating charge on both sides of a permselective membrane.

Separation of two ionic solutions with a permselective membrane that is impermeable to some of the ions leads to an uneven distribution of permeating ions on the two sides of the membrane described by the Gibbs-Donnan (G-D) equilibrium with the G-D factors relating ion concentrations in the two solutions. Here, we present a method of calculating the G-D factors for ideal electroneutral multi-ion solutions with different total charge of non-permeating species on each side of a permselective membrane separating two compartments. We discuss some special cases of G-D equilibrium for which an analytical solution may be found, and we prove the transitivity of G-D factors for multi-ion solutions in several compartments interconnected by permselective membranes. We show a few examples of calculation of the G-D factors for both simple and complex solutions, including the case of human blood plasma and interstitial fluid separated by capillary walls. The article is accompanied by an online tool that enables the calculation of the G-D factors and the equilibrium concentrations for multi-ion solutions with various composition in terms of permeating ions and non-permeating charge, according to the presented method.

Monitoring relative blood volume changes during hemodialysis: Impact of the priming procedure.

The monitoring of relative blood volume (RBV) changes during hemodialysis is increasingly used to evaluate the effect of dialyzer ultrafiltration on intravascular volume to guide the removal of excess fluid in a manner that maintains hemodynamic stability of the patient. RBV monitoring is typically based on an optical or acoustic sensor placed in the arterial blood line that measures a marker of hemoconcentration, such as hematocrit, hemoglobin, or total blood protein. However, the accuracy of RBV monitors and the impact of their clinical use remain the subject of ongoing debate. Here, we show that, depending on the procedure of filling the extracorporeal circuit with the patient's blood at the beginning of the dialysis session, the indications of an RBV monitor may be misleading as to the actual changes of the intravascular volume. When the blood is first pumped into the dialyzer, the priming fluid (saline) that fills the circuit may be either infused into the patient or disposed of to a drain bag. In the latter case, the intravascular volume is suddenly reduced, which is not accounted for by RBV monitors that track only the subsequent reductions in blood volume due to dialyzer ultrafiltration. We analyzed this general aspect of RBV monitoring using model-based simulations and showed quantitatively how RBV changes calculated using hematocrit differ depending on the priming procedure.

Transcapillary transport of water, small solutes and proteins during hemodialysis.

The semipermeable capillary walls not only enable the removal of excess body water and solutes during hemodialysis (HD) but also provide an essential mechanism for maintaining cardiovascular homeostasis. Here, we investigated transcapillary transport processes on the whole-body level using the three-pore model of the capillary endothelium with large, small and ultrasmall pores. The transcapillary transport and cardiovascular response to a 4-h hemodialysis (HD) with 2 L ultrafiltration were analyzed by simulations in a virtual patient using the three-pore model of the capillary wall integrated in the whole-body compartmental model of the cardiovascular system with baroreflex mechanisms. The three-pore model revealed substantial changes during HD in the magnitude and direction of transcapillary water flows through small and ultrasmall pores and associated changes in the transcapillary convective transport of proteins and small solutes. The fraction of total capillary hydraulic conductivity attributed to ultrasmall pores was found to play an important role in the transcapillary water transport during HD thus influencing the cardiovascular response to HD. The presented model provides a novel computational framework for a detailed analysis of microvascular exchange during HD and as such may contribute to a better understanding of dialysis-induced changes in blood volume and blood pressure.

Hemodialysis-induced changes in hematocrit, hemoglobin and total protein: Implications for relative blood volume monitoring.

BACKGROUND: Relative blood volume (RBV) changes during hemodialysis (HD) are typically estimated based on online measurements of hematocrit, hemoglobin or total blood protein. The aim of this study was to assess changes in the above parameters during HD in order to compare the potential differences in the RBV changes estimated by individual methods. METHODS: 25 anuric maintenance HD patients were monitored during a 1-week conventional HD treatment. Blood samples were collected from the arterial dialysis blood line at the beginning and at the end of each HD session. The analysis of blood samples was performed using the hematology analyzer Advia 2120 and clinical chemistry analyzer Advia 1800 (Siemens Healthcare). RESULTS: During the analyzed 30 HD sessions with ultrafiltration in the range 0.7-4.0 L (2.5 ± 0.8 L) hematocrit (HCT) increased by 9.1 ± 7.0% (mean ± SD), hemoglobin (HGB) increased by 10.6 ± 6.3%, total plasma protein (TPP) increased by 15.6 ± 9.5%, total blood protein (TBP) increased by 10.4 ± 5.8%, red blood cell count (RBC) increased by 10.8 ± 7.1%, while mean corpuscular red cell volume (MCV) decreased by 1.5 ± 1.1% (all changes statistically significant, p < 0.001). HGB increased on average by 1.5% more than HCT (p < 0.001). The difference between HGB and TBP increase was insignificant (p = 0.16). CONCLUSIONS: Tracking HGB or TBP can be treated as equivalent for the purpose of estimating RBV changes during HD. Due to the reduction of MCV, the HCT-based estimate of RBV changes may underestimate the actual blood volume changes.

Modeling Pathological Hemodynamic Responses to the Valsalva Maneuver.

The Valsalva maneuver (VM) consisting in a forced expiration against closed airways is one of the most popular clinical tests of the autonomic nervous system function. When properly performed by a healthy subject, it features four characteristic phases of arterial blood pressure (BP) and heart rate (HR) variations, based on the magnitude of which the autonomic function may be assessed qualitatively and quantitatively. In patients with some disorders or in healthy patients subject to specific conditions, the pattern of BP and HR changes during the execution of the Valsalva maneuver may, however, differ from the typical sinusoidal-like pattern. Several types of such abnormal responses are well known and correspond to specific physiological conditions. In this paper, we use our earlier mathematical model of the cardiovascular response to the Valsalva maneuver to show that such pathological responses may be simulated by changing individual model parameters with a clear physiological meaning. The simulation results confirm the adaptability of our model and its usefulness for diagnostic or educational purposes.

Mathematical modelling of cardiovascular response to the Valsalva manoeuvre.

The Valsalva manoeuvre (VM) used for clinical autonomic testing results in a complex cardiovascular response with a concomitant action of several regulatory mechanisms whose nonlinear interactions are difficult to analyse without the aid of a mathematical model. The article presents a new non-pulsatile compartmental model of the human cardiovascular system with a variable intrathoracic pressure enabling the simulation of the haemodynamic response to the VM. The model is based on physiological data and includes three baroreflex mechanisms acting on heart rate, systemic resistance and venous unstressed volume. New nonlinear functions have been proposed to model cardiac output dependence on preload and afterload. Following the individual fitting of some parameters with a clear physiological meaning, the model is able to fit clinical data from patients with both typical and abnormal haemodynamic response to the VM. The sensitivity analysis showed that the model is most sensitive to the parameters describing the vascular pressure-volume relationships (the maximal volume of systemic veins and the relative level of vascular compliance). The use of nonlinear pressure-volume relationships for systemic veins proved crucial for the accurate modelling of the VM. On the contrary, the introduction of aroreflex time delays did not change significantly the haemodynamic response to the manoeuvre. The model can be a useful tool for aiding the interpretation of patient's response to the VM and provides a framework for analysing the interactions between the cardiovascular system and autonomic regulatory mechanisms.