Endothelial dysfunction is the first pathophysiological step of atherosclerosis, which is responsible for 90% of strokes. Exercise programs aim to reduce the risk of developing stroke; however, the majority of the beneficial factors of exercise are still unknown. Endothelial shear stress (ESS) is associated with endothelial homeostasis. Unfortunately, ESS has not been characterized during different exercise modalities and intensities in the carotid artery. Therefore, the purpose of this study was to determine exercise-induced blood flow patterns in the carotid artery. Fourteen apparently healthy young adults (males = 7, females = 7) were recruited for this repeated measures study design. Participants completed maximal oxygen consumption (VO2max) tests on a Treadmill, Cycle-ergometer, and Arm-ergometer, and 1-repetition maximum (1RM) tests of the Squat, Bench Press (Bench), and Biceps Curl (Biceps) on separate days. Thereafter, participants performed each exercise at 3 different exercise intensities (low, moderate, high) while a real-time ultrasound image and blood flow of the carotid artery was obtained. Blood flow patterns were assessed by estimating ESS via Womersley’s estimation and turbulence via Reynold’s number (Re). Data were analyzed using a linear mixed-effects model. Pairwise comparisons with Holm-Bonferroni correction were conducted with Hedge’s g effect size to determine the magnitude of the difference. There was a main effect of intensity, exercise modality, and intensity * exercise modality interaction on both ESS (p < 0.001). Treadmill at a high intensity yielded the greatest ESS when compared to the other exercise modalities and intensities, while Bench Press and Biceps curls yielded the least ESS. All exercise intensities across all modalities resulted in turbulent blood flow. Clinicians must take into consideration how different exercise modalities and intensities affect ESS and Re of the carotid artery.

Endothelial shear stress (ESS) has a possible effect on regulation of gene expression in the protection against atherosclerosis. During exercise, ESS should increase as systolic blood pressure and heart rate (HR) increase too; however, it is hard to determine ESS changes during exercise. Imaging ultrasound assessment of the brachial and the carotid arterial blood flow during exercise might help to estimate exercise-induced ESS. We present here the methodology at the Clinical Applied Physiology Laboratory to estimate exercise-induced ESS. We normally perform 2 exercise tests in 2 different visits. First, a cardiopulmonary exercise test with serial microblood sampling to determine blood lactate (La) levels on a stationary cycle ergometer to determine maximal oxygen consumption, maximal exercising HR, and lactate threshold curve. The second exercise test includes three 5-min steady state stages determined by La levels from test 1 (La 4 mmol/L). During the second test, we position an ultrasound probe holder on either the arm or neck to image the brachial or carotid arteries, respectively. We obtain images and blood flow velocities through Doppler at each exercise stage and then we analyze the images using edge detection software to determine artery diameters. With these data, we are able to estimate ESS, flow direction, and the presence of turbulent flow.

Purpose: To determine whether exercise-induced levels of endothelial shear stress (ESS) observed in vivo upregulates endothelial protective proteins in vitro. Methods: In vivo carotid ESS was obtained from previously published data. Human umbilical vein endothelial cells were seeded in a collagen-coated Y-luer slides with a bifurcation that mimics the common carotid artery and its bifurcation. Four duplicate groups were exposed to 5 hours of resting ESS (18 dynes/cm²) followed by 1 hour of ESS at 18 dynes/cm² × heart rate (HR) 60 pulses per minute (ppm) (control), 35 dynes/cm² × HR 100 ppm (low), 50 dynes/cm² × HR 120 ppm (moderate), or 60 dynes/cm² × HR 150 ppm (high). After ESS exposure, cells were stained to identify cell nucleus, phosphorylated endothelial NO synthase (eNOSp), and intracellular actin concentrations using immunohistochemistry. Confocal microscopy images captured areas exposed to varying degrees of shear stress within the “common” artery, the bifurcation, and the distal branches of the bifurcation. Results: Images showed a higher expression of eNOSp and actin that is generally intensity and location dependent. High shear stress (HSS) showed the greatest eNOSp expression compared with all conditions at the after-bifurcation site (P < .05). Interestingly, HSS continued to result in greater expression of actin at the bifurcation site across all 4 intensities, where blood flow is known to be more turbulent. Conclusions: These findings may support the hypothesis that high shear stress plays an important protective endothelial role in relation to individualized exercise prescription as a contribution to precision medicine. Impact Statement: Endurance exercise intensity has a direct impact in endothelial cell homeostasis at the physiological and molecular levels. When a physical therapist prescribes endurance exercise for cardiovascular diseases, the goal should be to deliver precision medicine to enhance patient's health outcomes.

In veins, clotting initiation displays a threshold response to flow intensity and injury size. Mathematical models can provide insights into the conditions leading to clot growth initiation under flow for specific subjects. However, it is hard to determine the thrombin generation curves that favor coagulation initiation in a fast manner, especially when considering a wide range of conditions related to flow and injury size. In this work, we propose to address this challenge by using a neural network model trained with the numerical simulations of a validated 2D model for clot formation. Our surrogate model approximates the results of the 2D simulations, reaching an accuracy of 94% on the test dataset. We used the trained artificial neural network to determine the threshold for thrombin generation parameters that alter the coagulation initiation response under varying flow speed and injury size conditions. Our model predictions show that increased levels of the endogenous thrombin potential (ETP) and peak thrombin concentration increase the likelihood of coagulation initiation, while an elevated time to peak decreases coagulation. The lag time has a small effect on coagulation initiation, especially when the injury size is small. Our surrogate model can be considered as a proof-of-concept of a tool that can be deployed to estimate the risk of bleeding in specific patients based on their Thrombin Generation Assay results.

A randomized, double-blind, placebo-controlled, cross-over study where continuous therapeutic ultrasound (CUS; at 0.4 W/cm²), pulsed therapeutic ultrasound (PUS; at 20% duty cycle, 0.08 W/cm²), both at 1 MHz, and placebo (equipment on, no energy provided) were randomized and applied over the forearm of the non-dominant arm for 5 min in 10 young, healthy individuals. Absolute and peak forearm blood flow (FBF) were measured via Venous Occlusion Plethysmography. FBF was measured before, halfway, and after (immediately and 5 min after) the therapeutic ultrasound (TUS) intervention. Post-ischemic peak FBF was measured 10 min before and 10 min after the TUS intervention. A two-way repeated measures ANOVA (group × time) was selected to assess differences in FBF before, during, and after TUS treatment, and for peak FBF before and after TUS treatment. FBF increased 5 min after TUS in CUS compared to placebo (2.96 ± 1.04 vs. 2.09 ± 0.63 mL/min/100 mL of tissue, p < 0.05). PUS resulted in the greatest increase in Peak FBF at 10 min after US (Δ = 3.96 ± 2.02 mL/min/100 mL of tissue, p = 0.06). CUS at 1 MHz was an effective treatment modality for increasing FBF up to 5 min after intervention, but PUS resulted in the greatest increase in peak FBF at 10 min after intervention.