Windkessel Model Research Articles

Effects of systemic ventricular assist in failing Fontan patients: a theoretical analysis using a computational model

Mechanical circulatory support is a potential treatment for failing Fontan patients. In this study, we performed a theoretical analysis using a computational model to clarify the effects of systemic ventricular assist device (VAD) in failing Fontan patients. Cardiac chambers and vascular systems were described using the time-varying elastance model and modified Windkessel model, respectively. A VAD was simulated as a nonlinear function. In systolic and diastolic ventricular dysfunction and atrioventricular valve regurgitation models, systemic VAD increased the cardiac index and decreased the central venous pressure (CVP). However, in the high pulmonary vascular resistance model, CVP became extremely high above 15 mmHg to maintain the cardiac index when the pulmonary vascular resistance index (PVRI) was above 5 Wood units m2. In Fontan patients with ventricular dysfunction or atrioventricular valve regurgitation, systemic VAD efficiently improves the hemodynamics. In Fontan patients with PVRI of > 5 Wood units m2, systemic VAD seems ineffective.

Estimating pulmonary arterial remodeling via an animal-specific computational model of pulmonary artery stenosis.

Pulmonary artery stenosis (PAS) often presents in children with congenital heart disease, altering blood flow and pressure during critical periods of growth and development. Variability in stenosis onset, duration, and severity result in variable growth and remodeling of the pulmonary vasculature. Computational fluid dynamics (CFD) models enable investigation into the hemodynamic impact and altered mechanics associated with PAS. In this study, a one-dimensional (1D) fluid dynamics model was used to simulate hemodynamics throughout the pulmonary arteries of individual animals. The geometry of the large pulmonary arteries was prescribed by animal-specific imaging, whereas the distal vasculature was simulated by a three-element Windkessel model at each terminal vessel outlet. Remodeling of the pulmonary vasculature, which cannot be measured in vivo, was estimated via model-fitted parameters. The large artery stiffness was significantly higher on the left side of the vasculature in the left pulmonary artery (LPA) stenosis group, but neither side differed from the sham group. The sham group exhibited a balanced distribution of total distal vascular resistance, whereas the left side was generally larger in the LPA stenosis group, with no significant differences between groups. In contrast, the peripheral compliance on the right side of the LPA stenosis group was significantly greater than the corresponding side of the sham group. Further analysis indicated the underperfused distal vasculature likely moderately decreased in radius with little change in stiffness given the increase in thickness observed with histology. Ultimately, our model enables greater understanding of pulmonary arterial adaptation due to LPA stenosis and has potential for use as a tool to noninvasively estimate remodeling of the pulmonary vasculature.

P214 PREDICTION OF AMBULATORY BRACHIAL CUFF-BASED OSCILLOMETRIC PULSE WAVE VELOCITY USING A NOVEL METHOD FOR ESTIMATING TOTAL ARTERIAL COMPLIANCE

Background and Objective: Total arterial compliance (Ct) serves as a critical determinant of arterial hemodynamics, providing insights into the mechanical and structural characteristics of large arteries and influencing ventricular-arterial coupling. To estimate Ct, we developed a method utilizing data from 24-hour ambulatory blood pressure monitoring (24-h ABPM) recordings. Our objective is to evaluate the reliability of Ct in estimating oscillometric pulse wave velocity (oPWV), with the potential to eliminate the requirement for additional oPWV measurements. Methods: A cross-sectional study was conducted, involving 162 patients who underwent 24-h ABPM, resulting in a total of 8,113 blood pressure (BP) recordings. oPWV was measured during 24-h ABPM using a Custo Screen 310 device (Custo, Ottobrunn, Germany), which has been validated. Ct was estimated employing a two-element Windkessel model based on mean systolic pressure. The formula utilized for Ct estimation was Ct/BSA= (38/PPth)×(4/5)×(Td/T)-(3/7), where BSA denotes body surface area, Td represents diastolic time, T signifies the cardiac period, and PPth denotes theoretical pulse pressure. A linear regression model (LRM) was developed to estimate oPWV from Ct. Results: Among the participants, 55.1% were men, with an average age of 55.7±16.2 years and a body mass index of 27.4±3.7 kg/m2. The analyzed records revealed an average systolic blood pressure of 125.6±18.7 mmHg, diastolic blood pressure of 79.5±12.2 mmHg, heart rate of 71.0±12.2 beats per minute, Ct of 0.9±0.3 mL/mmHg, and oPWV of 7.2±1.8 m/s. The best predictive model (R2=0.42; r=0.65) for oPWV was based on the ratio of systolic time (Ts) to Ct as follows: oPWV=3.3 × 6.0 ×[Ts/(Ct/BSA)]. Indexed Ct demonstrated an inverse relationship with oPWV (Figure). Residuals analysis confirmed compliance with assumptions. Conclusions: The Ts/Ct ratio inversely predicts oPWV, indicating an inverse relationship between Ct and oPWV in this population. These findings suggest that estimated Ct has the potential to replace oPWV in clinical practice for cardiovascular risk stratification.

No influence of steady-state postural changes on cerebrovascular compliance in humans.

The aim of this study was to determine the effect of posture changes on vascular compliance in intracranial (brain) versus extracranial vascular beds (forearm). Eighteen young adults (nine females) performed a supine-to-seated-to-standing protocol involving 5 min of rest in each position. Continuous blood pressure, middle cerebral artery (MCA) blood velocity, and brachial artery blood velocity were recorded at each posture. Three to five consecutive steady-state cardiac cycles at each posture were analyzed by a four-element lumped parameter modified Windkessel model to calculate vascular compliance. Mean arterial pressure (MAP) increased from supine to seated (76(9) vs. 81(12) mmHg; P=0.006) and from supine to standing (76(9) vs. 82(13) mmHg; P=0.034). Mean blood flow was greater in the MCA relative to the forearm (forearm: 40(5) mL·min-1, MCA: 224(17) mL·min-1; main effect P<0.001). Conversely, vascular resistance (forearm: 3.25(0.50) mmHg-1·mL·min-1, brain: 0.36(0.04) mmHg-1·mL·min-1; main effect P<0.001) and compliance (forearm: 0.010(0.001) mL·min-1·mmHg-1, brain: 0.005(0.001) mL·min-1·mmHg-1; main effect P=0.001) were greater in the forearm compared to the brain. Significant main effects of posture were observed with decreasing values in upright positions for mean blood flow (P=0.001) in both vascular beds, but not for resistance (P=0.163) or compliance (P=0.385). There were no significant interaction effects between vascular bed and posture for mean flow (P=0.057), resistance (P=0.258), or compliance (P=0.329). This study provides evidence that under steady-state conditions, posture does not affect cerebrovascular compliance.

Design of a pharmacokinetic/pharmacodynamic model for administration of low dose peripheral norepinephrine during general anaesthesia.

Intraoperative hypotension is a risk factor for kidney, heart and cognitive postoperative complications. Literature suggests that the use of low-dose peripheral norepinephrine (NOR) reduces organ dysfunction, yet its administration remains unstandardized. In this work we develop a pharmacokinetic (PK)/pharmacodynamic (PD) model of NOR and its effect on mean arterial pressure (MAP). From June 2018 to December 2021, we included patients scheduled for elective neurosurgery and requiring vasopressors for intraoperative hypotension management at Lariboisière Hospital, Paris. Low doses of NOR were administered peripherally, and successive arterial blood samples were collected to track its plasmatic concentration. We used a compartmental modelling approach for NOR PK. We developed and compared 2 models for NOR PD on MAP. Model comparison was done using Bayes information criteria. The resulting PK/PD model parameters were fitted over the entire population and linked to age, weight, height and sex. We included 29 patients (age 52 [46-64] years, 69% female). NOR median time to peak effect on MAP was 74 [53-94] s. After bolus administration, MAP increased by 24% (15-31%). A 2-comparment model with depot best captured NOR PK. NOR PD effect on MAP was well represented by both Emax and Windkessel models, with better results for the former. We found that age, height and weight as well as history of smoking and hypertension were correlated with model parameters. We have developed a PK/PD model to accurately track norepinephrine plasma concentration and its effect on MAP over time, which could serve for target-controlled infusion.

Influence of angiotensin II and telmisartan on in vivo high-resolution renal arterial impedance in rats.

Angiotensin II (ANG II) is known to play an important role in regulating renal hemodynamics. We sought to quantify this effect in an in vivo rat model with high-resolution renal arterial (RA) impedance. This study examines the effects of ANG II and its type 1 receptor blocker telmisartan (TELM) on RA impedance. In baroreflex-deactivated rats, we measured RA pressure (Pr) and blood flow (Fr) during random ventricular pacing to induce pressure fluctuation at three different mean Pr (60, 80, and 100 mmHg). We then estimated RA impedance as the transfer function from Fr to Pr. The RA impedance was found to align with a three-element Windkessel model consisting of proximal (Rp) and distal (Rd) resistance and compliance (C). Our study showed Rd reflected the composite characteristics of afferent and efferent arterioles. Rd increased with increasing Pr under the baseline condition with a slope of 1.03 ± 0.21 (× 10-1) min·mL-1. ANG II significantly increased the slope by 0.72 ± 0.29 (× 10-1) min·mL-1 (P < 0.05) without affecting the intercept. TELM significantly reduced the intercept by 34.49 ± 4.86 (× 10-1) mmHg·min·mL-1 (P < 0.001) from the baseline value of 37.93 ± 13.36 (× 10-1) mmHg·min·mL-1, whereas it did not affect the slope. In contrast, Rp was less sensitive than Rd to ANG II or TELM, suggesting Rp may represent the characteristics of elastic large arteries. Our findings provide valuable insights into the influence of ANG II on the dynamics of the renal vasculature.NEW & NOTEWORTHY This present method of quantifying high-resolution renal arterial impedance could contribute to elucidating the characteristics of renal vasculature influenced by physiological mechanisms, renal diseases, or pharmacological effects. The present findings help construct a lumped-parameter renal hemodynamic model that reflects the influence of angiotensin II.

Non-invasive fractional flow reserve estimation in coronary arteries using angiographic images

Coronary artery disease is the leading global cause of mortality and Fractional Flow Reserve (FFR) is widely regarded as the gold standard for assessing coronary artery stenosis severity. However, due to the limitations of invasive FFR measurements, there is a pressing need for a highly accurate virtual FFR calculation framework. Additionally, it’s essential to consider local haemodynamic factors such as time-averaged wall shear stress (TAWSS), which play a critical role in advancement of atherosclerosis. This study introduces an innovative FFR computation method that involves creating five patient-specific geometries from two-dimensional coronary angiography images and conducting numerical simulations using computational fluid dynamics with a three-element Windkessel model boundary condition at the outlet to predict haemodynamic distribution. Furthermore, four distinct boundary condition methodologies are applied to each geometry for comprehensive analysis. Several haemodynamic features, including velocity, pressure, TAWSS, and oscillatory shear index are investigated and compared for each case. Results show that models with average boundary conditions can predict FFR values accurately and observed errors between invasive FFR and virtual FFR are found to be less than 5%.

Efficient Cardiovascular Parameters Estimation for Fluid-Structure Simulations Using Gappy Proper Orthogonal Decomposition.

As full-scale detailed hemodynamic simulations of the entire vasculature are not feasible, numerical analysis should be focused on specific regions of the cardiovascular system, which requires the identification of lumped parameters to represent the patient behavior outside the simulated computational domain. We present a novel technique for estimating cardiovascular model parameters using gappy Proper Orthogonal Decomposition (g-POD). A POD basis is constructed with FSI simulations for different values of the lumped model parameters, and a linear operator is applied to retain information that can be compared to the available patient measurements. Then, the POD coefficients of the reconstructed solution are computed either by projecting patient measurements or by solving a minimization problem with constraints. The POD reconstruction is then used to estimate the model parameters. In the first test case, the parameter values of a 3-element Windkessel model are approximated using artificial patient measurements, obtaining a relative error of less than 4.2%. In the second case, 4 sets of 3-element Windkessel are approximated in a patient's aorta geometry, resulting in an error of less than 8% for the flow and less than 5% for the pressure. The method shows accurate results even with noisy patient data. It automatically calculates the delay between measurements and simulations and has flexibility in the types of patient measurements that can handle (at specific points, spatial or time averaged). The method is easy to implement and can be used in simulations performed in general-purpose FSI software.

Rapid changes in cerebrovascular compliance during vasovagal syncope.

The compensatory mechanisms supporting cerebral perfusion throughout head-up tilt (HUT) in patients with vasovagal syncope (VVS) remain unclear. We tested the hypothesis that increased cerebrovascular compliance (Ci) and decreased cerebrovascular resistance (CVR) support cerebral blood velocity (CBV) during pre-syncope in VVS. Finger arterial blood pressure (ABP) and right middle cerebral artery blood velocity (CBV) were recorded in 15 individuals diagnosed with VVS (n = 11 female, mean age: 40 ± 16years, mean body mass index: 24.9 ± 4.0kg/m2) at supine rest and during HUT (80 degree angle). Individual ABP and CBV waveforms during VVS were input into a modified Windkessel model to calculate Ci and ohmic CVR. Gosling's pulsatility index (Pi; pulse amplitude/mean CBV) was calculated. Diastolic ABP, systolic ABP, mean ABP (72 ± 11 to 51 ± 12mmHg), and CVR decreased progressively during presyncope (all P ≤ 0.04). As expected, systolic CBV was sustained (all P ≥ 0.29) while diastolic and mean CBV (51 ± 13 to 38 ± 13mmHg) fell during presyncope (all P ≤ 0.04). Both Ci and Pi increased during presyncope (128 ± 97 and 60 ± 41%, respectively; all P ≤ 0.049) and were positively correlated (R2 = 0.79, P < 0.01). Increased Ci contributed to changes in mean CBV (P < 0.01) but decreased CVR did not (P = 0.28). These data provide evidence that Ci increases during presyncope in patients with VVS and is likely involved in the maintenance of systolic CBV during a fall in diastolic CBV. However, this regulation is not sufficient to preserve CBV in the presence of such extreme and progressive reductions in ABP.

The origin of intraluminal pressure waves in gastrointestinal tract.

The gastrointestinal (GI) peristalsis is an involuntary wave-like contraction of the GI wall that helps to propagate food along the tract. Many GI diseases, e.g., gastroparesis, are known to cause motility disorders in which the physiological contractile patterns of the wall get disrupted. Therefore, to understand the pathophysiology of these diseases, it is necessary to understand the mechanism of GI motility. We present a coupled electromechanical model to describe the mechanism of GI motility and the transduction pathway of cellular electrical activities into mechanical deformation and the generation of intraluminal pressure (IP) waves in the GI tract. The proposed model consolidates a smooth muscle cell (SMC) model, an actin-myosin interaction model, a hyperelastic constitutive model, and a Windkessel model to construct a coupled model that can describe the origin of peristaltic contractions in the intestine. The key input to the model is external electrical stimuli, which are converted into mechanical contractile waves in the wall. The model recreated experimental observations efficiently and was able to establish a relationship between change in luminal volume and pressure with the compliance of the GI wall and the peripheral resistance to bolus flow. The proposed model will help us understand the GI tract's function in physiological and pathophysiological conditions.

#2795 In-silico assessment of arteriovenous fistula maturation with patient-specific computational hemodynamic models

Abstract Background and Aims Native arteriovenous fistula (nAVF) is the preferred access for haemodialysis (HD) treatment. Both the quality and complications of the haemodialysis technique are closely related to vascular access. nAVF maturation process includes several morphological changes affecting haemodynamics, with previous studies suggesting that it is highly related to AVF failure. Computational Fluid Dynamics (CFD) simulations by using idealized morphologies or the analysis of one patient-specific geometry have been proposed to understand the pathophysiology of maturation failure. However, it is difficult to correlate with clinical practice and therefore limits its use. The aim is to develop a patient-specific modelling time pipeline, incorporating the haemodynamics of the blood flow to real anatomical and morphological characteristics. Method Design: prospective computational simulation analysis of nAVF in 3 patients at 3 different stages: after fistula creation, (1 week), maturation (1 month) and post-maturation (6 months). Analysis: morphological and haemodynamic. Inclusion criteria: &amp;gt;18 years and end-stage chronic kidney disease. Variables and data: Once morphology was extracted from nAVF magnetic resonance imaging, generated meshes were refined and compiled to obtain a volumetric mesh. The boundary conditions of the model were defined and extracted using ultrasound nAFV data. Data were analyzed at the 3 stages. Models: A 3-element Windkessel model was used to simulate the pressure waveform to feed the vein of the system. In this model, clinical data were also considered to classify the patient as normotensive or hypertensive to estimate waveform parameters. The Windkessel model estimates wall shear stress (WSS), velocity and flow for all the points located in the mesh by making an analogy from an electric circuit resistance model. As validation, the flow obtained from the Windkessel model was compared with the one obtained from the ultrasound scan of the patient. Results Different temporal points were analyzed for each nAVF. Results from the simulations in Fig. 1, illustrating the evolution over time and development. The geometrical characteristics were found to significantly impact on flow dynamics. The area most affected by flow was the juxta-anastomotic section which showed higher magnitude distribution of WSS and velocity for all time-points. According to the analysis of the simulations, a perpendicular junction between the vein and the artery potentially resulted in less damage in this area (in WSS terms), being important to mitigate the AVF failure. At maturation stage (1 month) the analysis shows WSS distribution mainly located in the juxta-anastomotic section and decreased in magnitude regarding one week; therefore, this can be marked as the stabilization point for nAFV maturation. Conclusion

Boundary Condition Options for Carotid Bifurcation Analysis, Using Doppler Velocity Measurements

The Common Carotid Artery plays a vital role in supplying the brain, and its bifurcation is susceptible to vascular diseases. It is often analyzed using computational fluid dynamics (CFD) simulations, but it is challenging to prescribe boundary conditions that approach patient-specific flow conditions. We examined six boundary condition (BC) groups to determine the most accurate flow conditions aligning with available measured data. We conducted CFD simulations on a stenotic carotid bifurcation, using patient-specific Doppler ultrasound sonography velocity measurements at the inlet and both outlets. Three BC methods used defined inlet flow rate and either constant pressure (Basic), Windkessel model, or constant flow ratio (Murray) at the outlets. Three other methods were defined with flow rates at two boundaries and constant pressure at the third one. Defining two boundary flow rates shows the closest results to physiologically valid data. However, the difficult Doppler measurements on the outlet branches can inaccurately amplify velocity amplitudes and may detect a false flow direction. Therefore, cross-sectional corrections were implemented to fit the outlet and inlet flow rates, while keeping the measured velocity histories.Our results show that the Murray and Basic methods, while easily available, exclude carotid-specific flow conditions by disregarding downstream flow resistances. We conclude that a Windkessel-method can produce the most accurate results without forcing outflow conditions. However, usually unavailable measurements are necessary for its application. Simulations with outlet-defined volume flow can also produce physiologically valid solutions but require the application of cross-sectional geometry correction.

Transient Performance Analysis of Centrifugal Left Ventricular Assist Devices Coupled With Windkessel Model: Large Eddy Simulations Study on Continuous and Pulsatile Flow Operation.

Computational fluid dynamics (CFD) simulations are widely used to develop and analyze blood-contacting medical devices such as left ventricular assist devices (LVADs). This work presents an analysis of the transient behavior of two centrifugal LVADs with different designs: HeartWare VAD and HeartMate3. A scale-resolving methodology is followed through Large Eddy Simulations, which allows for the visualization of turbulent structures. The three-dimensional (3D) LVAD models are coupled to a zero-dimensional (0D) 2-element Windkessel model, which accounts for the vascular resistance and compliance of the arterial system downstream of the device. Furthermore, both continuous- and pulsatile-flow operation modes are analyzed. For the pulsatile conditions, the artificial pulse of HeartMate3 is imposed, leading to a larger variation of performance variables in HeartWare VAD than in HeartMate3. Moreover, CFD results of pulsatile-flow simulations are compared to those obtained by accessing the quasi-steady maps of the pumps. The quasi-steady approach is a predictive tool used to provide a preliminary approximation of the pulsatile evolution of flow rate, pressure head, and power, by only imposing a speed pulse and vascular parameters. This preliminary quasi-steady solution can be useful for deciding the characteristics of the pulsatile speed law before running a transient CFD simulation, as the former entails a significant reduction in computational cost in comparison to the latter.

The effect of baroreflex-induced sympathetic suppression on renal arterial impedance in rats

Objective: We examined the effect of baroreflex on renal arterial impedance (ZRA) to gain insights into renal hemodynamics and local autoregulation. Methods: This study involved male Wistar-Kyoto rats (n = 6). We measured renal arterial pressure (PRA) and renal arterial flow (FRA). For high-resolution renal arterial impedance (ZRA) over the frequency range of 0.1-70 Hz, random pacing was employed. We isolated the bilateral carotid sinus baroreceptor regions and utilized a servo pump to control carotid sinus pressure (CSP) either at 60 mmHg or 140 mmHg. We controlled mean arterial pressure (AP) at 100 mmHg (AP-fix) or allowed to vary in response to changes in CSP (AP-variable). A three‐element Windkessel (3-WK) model was used to quantify ZRA (R1: proximal resistance, R2: distal resistance, and C: renal compliance). Results: With AP-fix, an increase of CSP from 60 mmHg to 140 mmHg did not change mean PRA (99.85 ± 0.16 vs. 98.00 ± 1.22 mmHg, P = ns) or mean FRA (8.73 ± 0.41 vs. 8.10 ± 0.38 min/mL, Δ = −7%, P = ns). This rise of CSP did not significantly affect R1 (0.74 ± 0.11 vs. 0.61 ± 0.12 mmHg·min/mL, P = ns) or R2 (8.13 ± 1.08 vs. 8.79 ± 0.85 mmHg·min/mL, P = ns), but it did increase C by 20% (4.05 ± 0.47 vs. 4.88 ± 0.35 (×10−5) mL/mmHg, P &lt; 0.05). With AP-variable, elevating CSP from 60 mmHg to 140 mmHg significantly lowered mean PRA by 38% (105.42 ± 2.84 vs. 65.15 ± 4.87 mmHg, P &lt; 0.01), but did not change mean FRA (9.00 ± 0.48 vs. 7.92 ± 0.66 min/mL, Δ = −12%, P = ns). Changes in CSP did not affect R1 (0.77 ± 0.12 vs. 1.23 ± 0.24 mmHg·min/mL, P = ns), but they did reduce R2 by 41% (8.01 ± 1.08 vs. 4.76 ± 0.79 mmHg·min/mL, P &lt; 0.01) and increase C almost five-fold (3.79 ± 0.36 vs. 22.16 ± 6.91 (×10−5) mL/mmHg, P &lt; 0.05). Conclusion: The minor change in FRA (−12%) despite a 38% drop in PRA suggests the presence of local autoregulation to buffer changes in renal blood flow. The primary effect of renal hemodynamic regulation on ZRA was found in R2. When AP was allowed to vary in response to changes in CSP, increasing CSP, the baroreflex-induced sympathetic suppression decreased R2. However, when AP was held constant at 100 mmHg, the reduction in R2 was not observed, even with baroreflex activation resulting from changes in CSP. Hence, the local renal autoregulation may counteract the baroreflex, maintaining renal blood flow unchanged. Such a mechanism serves to protect the glomeruli from exogenously induced high mean AP. NTT Research, Inc. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Hemodynamic assessment of severely stenotic carotid arteries

Internal carotid artery (CA) stenosis is a primary etiological factor for stroke and transient ischemic attack. The severity of arterial stenosis significantly impacts patient health and treatment decisions. Therefore, we conducted computational fluid dynamics analyses on five carotid arteries (CAs) of severe stenosis and compared them with five CAs in the control group. We improved the three-element Windkessel model method by pre-calculating the constant-pressure outlet simulation of the first cardiac cycle, which accelerated the stability of the model. The research results show that vortices were observed at the bifurcation of the CAs in the control group, whereas in the severe stenosis group, vortices predominantly occurred within the carotid sinus downstream of the stenotic segment. Notably, the vortex flow in the carotid aneurysm downstream of the stenotic segment arises due to the cross-sectional constriction induced by stenosis, which always flows in a clockwise direction and may contribute to the formation of aneurysms distal to the stenotic region. A high time-averaged wall shear stress value can effectively identify the stenosis site of CAs, while a high relative residence time value marks the protrusion near the stenosis segment. This study delved into the hemodynamic parameters between the CAs of the severe stenosis group and the control group and provided robust clinical evidence for carotid atherosclerotic disease.

Rapid Changes in Cerebrovascular Compliance During Vasovagal Syncope

Background: The rapid reduction in arterial blood pressure (ABP) during vasovagal syncope (VVS) is associated with a characteristic decline in diastolic cerebral blood velocity (CBV) and maintained systolic CBV as measured by transcranial Doppler. This increased pulsatility was originally considered to be indicative of a “dysfunctional” increase in cerebrovascular resistance (CVR). Conversely, it may be due to increased cerebrovascular compliance (Ci) that partially attenuates the cerebral effects of rapid hypotension. We tested the hypothesis that Ci supports CBV during pre-syncope in VVS. Method: Finger ABP and right middle cerebral artery blood velocity (MCAv) were recorded from 15 otherwise healthy patients (n = 11 female, 40 ± 16 years, 24.9 ± 4.0 kg/m2) at rest and during head-up tilt (80°, 5 to 28 min). Individual ABP and CBV waveforms of every second heartbeat during VVS were input into a modified Windkessel model to calculate Ci and CVR. MCAv pulsatility was determined as pulse amplitude (systolic MCAv-diastolic MCAv) and Pulsatility Index (Pi; pulse amplitude/mean MCAv). Linear mixed models assessed the contribution of Ci to changes in CBV and Pi. Within-subject mediation analysis investigated the possibility of Ci mediating the relation between blood pressure (i.e., mean ABP and pulse pressure, PP) and cerebrovascular pulsatility. Results: Diastolic and systolic ABP decreased progressively during presyncope, resulting in a nadir reduction of mean ABP of Δ24 ± 9 mmHg at end-tilt (all p ≤ 0.04 vs mid-tilt). Mean MCAv decreased by 22 ± 12% prior to end-tilt (p &lt; 0.01 vs mid-tilt). CVR decreased progressively for 10s prior to end-tilt (p ≤ 0.04 vs mid-tilt). Pi increased significantly, with peak increases occurring at 4 s prior to end-tilt (77 ± 50%, p &lt; 0.01 vs mid-tilt). The increase in Ci (307 ± 223%, p &lt; 0.01 vs mid-tilt) significantly contributed to changes in MCAv (χ2 =10.6, p &lt; 0.01) and Pi (χ2 = 4.9, p = 0.03). Correlations of PP and ABP with Pi were not significant. However, PP was related to MCAv pulse amplitude (total effect: b = 1.57) and Ci ( b = -0.01, both p &lt; 0.01). Ci partially mediated (indirect effect: b = -0.78, p &lt; 0.01) the direct relation between PP and MCAv pulse amplitude ( b = 0.79, p = 0.01). Conclusion: These data provide evidence that Ci attenuates the fall in CBV under conditions of falling PP. Cerebrovascular regulation in VVS appears to be functioning as in healthy populations. However, this regulation is not suffcient to preserve flow in the presence of such extreme and rapid reductions in ABP. USRI — Western University, Natural Sciences and Engineering Research Council of Canada (NSERC, Grant No. RGPIN-2018-06255). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Cerebrovascular Compliance during Progressive Hypotension in Patients with Autonomic Failure

Background: Cerebral perfusion during reductions in arterial pressure (AP) can be supported transiently by a Windkessel mechanism that increases cerebrovascular compliance (Ci). This defense mechanism exists in healthy participants during rapid standing and in patients during vasovagal syncope. However, it remains unknown whether the rise in Ci with falling AP exhibits a threshold effect. Thus, we tested the hypothesis that increased Ci is passive to a reduction in AP and starts to increase only after a threshold has been reached. To test this hypothesis, it was necessary to study a population that tolerates progressive large reductions in BP without a loss of consciousness. Therefore, we analyzed Ci changes during a graded head-up tilt (HUT) from patients with autonomic failure (AF). Methods: Finger AP and right middle cerebral artery blood velocity (MCAv) were recorded from 5 AF patients (n = 5 male, 61 ± 23 years, 25 ± 5 kg/m2) at supine rest and during graded-HUT (30, 45, 60 degrees). Tilt gradients increased incrementally every 5 minutes until AP reached a critically low value prompting termination of HUT. The total time in HUT was 11 ± 4 min. Individual AP and MCAv waveforms during supine rest and graded HUT (one waveform every 5 s) were assessed with a modified Windkessel model to calculate Ci and cerebrovascular resistance (CVR). Pulse pressure (PP) was calculated as systolic AP − diastolic AP. A threshold value for the increase in Ci was determined as five consecutive cardiac cycles greater than the average supine Ci plus 2 standard deviations. Results: Graded HUT resulted in an overall reduction in AP (85 ± 18 to 50 ± 7 mmHg), PP (72 ± 22 to 32 ± 19 mmHg), mean MCAv (62 ± 12 to 35 ± 7 cm/s), and CVR (1.4 ± 0.1 to 1.0 ± 0.3 mmHg/cm/s; all p &lt; 0.05 vs supine). Ci increased by 905 ± 756% (p = 0.04 vs supine). The threshold effect was evident as Ci began to increase progressively after PP fell by 15 ± 3 mmHg and AP fell by 12 ± 2 mmHg. Conclusions: Our results provide evidence that Ci increases after a threshold reduction in PP and AP in the apparent absence of autonomic support. These data support the idea that increasing Ci during reductions in AP represents a pressure-dependent Windkessel mechanism. Of interest, our findings provide clinical insight into how AF patients compensate for such large reductions in pressure without the assistance of CVR as a defense mechanism. NSERC USRA — Western University, Natural Sciences and Engineering Research Council of Canada (NSERC, Grant No. RGPIN-2018-06255). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Abstract 1145: A Computational Fluid Dynamics Analysis Of Hemodynamic Differences In Patients With High Grade Asymptomatic Carotid Artery Stenosis

Introduction: Current assessment/management of internal carotid artery (ICA) stenosis is based on estimation of percentage (%) stenosis which does not account for trans-lesional flow, pressure gradient (PG), wall shear stress (WSS), or oscillatory shear index (OSI). Computation fluid dynamics (CFD) can be used to characterize such indices. Hypothesis: We hypothesize that patients asymptomatic &gt;70% ICA stenosis will have hemodynamic differences that are independent of % stenosis. Aims: Evaluate hemodynamic indices in patients with asymptomatic &gt;70% ICA stenosis via CFD. Methods: Patients with asymptomatic &gt;70% ICA stenosis were included. 3D time-of-flight (TOF) and phase-contrast (PC) magnetic resonance imaging (MRI) sequences were obtained. CRIMSON was used to generate CFD models containing the carotid artery (CCA), ICA, and external carotid artery (ECA). PC MRI-derived flow waveforms were prescribed to the CCA and ECA. The ICA outlet was coupled to a three-element Windkessel model. Blood was modeled as an incompressible Non-Newtonian fluid with a dynamic viscosity of 0.004 kg m –1 s –1 and a density of 1,060 kg m -3 . Incompressible Navier-Stokes equations were used to solve for velocity and pressures. Results: Eight patients (average age 73.8 years, 62.5% male) with asymptomatic high-grade ICA stenosis (62.5% left) were included. Hypertension (87.5%), tobacco use (87.5%), and hyperlipidemia (75%) were common. Most patients were medically optimized with anti-hypertensive (100%), statin (87.5%), and aspirin (87.5%). Three patients (37.5%) underwent ICA intervention.. Mean peak systolic velocity was 406 cm/s and mean end-diastolic velocity was 127 cm/s. There was large variability in trans-lesional ICA flow, PG, WSS, and OSI (Table 1). Conclusions: Asymptomatic patients with the same % stenosis have differences in trans-lesional ICA flow, PG, WSS, and OSI. Future work is needed to determine the prognostic value of such differences.

Impact of Peripheral Versus Central Insulin on Cerebrovascular Compliance in Healthy Young Adults

Objective: Vascular compliance is an essential component of cerebral blood flow regulation. Prior work has shown cerebral vasodilation (elicited by hypercapnia) reduces cerebrovascular compliance (Ci); however, this work has yet to be translated to other vasoactive compounds. Insulin has important vasodilatory effects in the peripheral circulation, but less is known about the role of insulin in cerebrovascular control. Herein, we hypothesized both peripheral (intravenous) and central (intranasal) insulin administration would increase indices of cerebral blood flow and reduce Ci in healthy young adults. Methods: Twenty-five healthy young adults (8 female; 26±7 yrs, 25±3 kg/m2) were assigned to two separate protocols (NCT05244694, NCT05153395). Middle cerebral artery blood velocity (MCAv, transcranial Doppler ultrasound) was measured at baseline and under two study conditions: 1) at the end of a 60 min hyperinsulinemic euglycemic infusion, and 2) 60 min following 160 IU of intranasal insulin. Indices of Ci were calculated using a modified Windkessel model applied to blood pressure (finger photoplethysmography) and corresponding MCAv waveforms collected over a 5-min period (10 waveforms) at baseline and during the aforementioned insulin conditions. Results: Blood glucose remained unchanged throughout both protocols (both p&gt;0.05). MCAv was maintained over time under both insulin conditions (protocol 1: 60±13 to 62±17 cm/s, p=0.635; protocol 2: 58±9 to 53±14 cm/s, p=0.146). In contrast, Ci decreased (0.00028±0.00010 to 0.00021±0.00007 cm/s/mmHg, p=0.010) from baseline during peripheral (intravenous) insulin administration. No change in Ci (0.00049±0.00025 to 0.00040±0.00018 cm/s/mmHg, p=0.189) were observed following intranasal insulin administration. Conclusions: Contrary to our hypothesis, there was no effect of peripheral or central insulin administration on resting MCAv in healthy young adults. However, intravenous (but not intranasal) insulin reduced Ci by approximately 25% from baseline values. These findings advance our understanding of cerebrovascular control mechanisms during insulin exposure and provide the opportunity to extend this work to diseased states characterized by insulin resistance, including diabetes. CAFNR Joy of Discovery (JKL, JP). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Enhancing the implantation of mechanical circulatory support devices using computational simulations.

Introduction: Patients with end-stage heart failure (HF) may need mechanical circulatory support such as a left ventricular assist device (LVAD). However, there are a range of complications associated with LVAD including aortic regurgitation (AR) and thrombus formation. This study assesses whether the risk of developing aortic conditions can be minimised by optimising LVAD implantation technique. Methods: In this work, we evaluate the aortic flow patterns produced under different geometrical parameters for the anastomosis of the outflow graft (OG) to the aorta using computational fluid dynamics (CFD). A three-dimensional aortic model is created and the HeartMate III OG positioning is simulated by modifying (i) the distance from the anatomic ventriculo-arterial junction (AVJ) to the OG, (ii) the cardinal position around the aorta, and (iii) the angle between the aorta and the OG. The continuous LVAD flow and the remnant native cardiac cycle are used as inlet boundaries and the three-element Windkessel model is applied at the pressure outlets. Results: The analysis quantifies the impact of OG positioning on different haemodynamic parameters, including velocity, wall shear stress (WSS), pressure, vorticity and turbulent kinetic energy (TKE). We find that WSS on the aortic root (AoR) is around two times lower when the OG is attached to the coronal side of the aorta using an angle of 45° ± 10° at a distance of 55mm. Discussion: The results show that the OG placement may significantly influence the haemodynamic patterns, demonstrating the potential application of CFD for optimising OG positioning to minimise the risk of cardiovascular complications after LVAD implantation.