Early return and increased magnitude of wave reflection augments pulsatile load, wastes left ventricular effort, and is associated with cardiovascular events. Acute handgrip (HG) exercise increases surrogate measures of wave reflection such as augmentation index. However, augmentation index does not allow distinguishing between timing vs. magnitude of wave reflection, and is affected by factors other than wave reflection per se. Wave separation analysis decomposes central pressure into relative contributions of forward (Pf) and backward (Pb) pressure wave amplitudes to calculate reflection magnitude (RM=Pb/Pf) and determine the timing of apparent wave reflection return. We tested the hypothesis that acute dynamic and isometric HG exercise increase RM and decrease reflected wave transit time (RWTT). Applanation tonometry was used to record radial artery pressure waveforms in 30 adults (25±4 years) at baseline and during dynamic and isometric HG exercise. Wave separation analysis was performed offline using a physiologic flow wave to derive Pf, Pb, RM, and RWTT. We found that RM increased during dynamic and isometric HG exercise compared to baseline (p=0.04 and p<0.01, respectively; baseline 40±5, dynamic 43±6, isometric 43±7%). Meanwhile, RWTT decreased during dynamic and isometric HG exercise compared to baseline (p=0.03 and p<0.001, respectively; baseline 164±23, dynamic 155±23, isometric 148±20 ms). Moreover, the changes in RM and RWTT were not different between dynamic and isometric HG exercise. The present data suggest wave reflection timing (RWTT) and magnitude (RM) are important factors that contribute to increased central blood pressure during HG exercise.

Introduction: Aberrant vascular function contributes to the substantially high cardiovascular burden of chronic kidney disease (CKD). Mitochondrial derived oxidative stress is a potential therapeutic target to ameliorate CKD related vascular dysfunction. Hypothesis: We hypothesized that a mitochondrial targeted antioxidant (MitoQ) would improve vascular function in Stage 3-5 CKD patients without overt cardiovascular disease. Methods: In this controlled, double-blind trial, 18 CKD patients (Mean±SEM: Age, 62±3 years; eGFR, 45±3 ml•min•1.73 2 ) were randomized to receive an oral dose of MitoQ (20mg/day; MTQ) or a Placebo (PLB) for 4 weeks. Outcome measures were assessed at week 0 and week 4. Aortic pressure waves were synthesized from brachial artery waveforms acquired by oscillometry and the use of a generalized transfer function. The central pressure waveform was separated into forward and reflected waves using a triangular flow waveform. Conduit artery vascular function was assessed via brachial artery flow mediated dilation (FMD). Results: MitoQ was well tolerated and patient compliance was high (MTQ, 99.6±0.4%; PLB, 97.8±2.2%). Independent of peripheral (Baseline vs. Follow Up: MTQ, 140±6 vs. 137±6 mmHg; PLB, 136±4 vs. 134±6 mmHg; interaction p=0.7) and central (MTQ, 128±5 vs. 123±6 mmHg; PLB, 124±3 vs. 123±5 mmHg; interaction p=0.8) systolic blood pressures, MitoQ maintained forward wave amplitudes (MTQ, 31±3 vs. 29±1 mmHg; PLB, 29±3 vs. 36±3 mmHg; interaction p=0.05) and tended to reduce reflected wave amplitudes (MTQ, 18±2 vs. 16±1 mmHg; PLB, 19±2 vs. 21±2 mmHg; interaction p=0.04). MitoQ administration favored improvements in FMD (MTQ, 2.4±0.3 vs. 4.0±0.9%; PLB, 4.2±1.0 vs. 2.5±1.0%; interaction p=0.04). Conclusions: These results suggest that targeting mitochondrial derived reactive oxygen species holds promise as a potential therapeutic strategy to improve CKD related vascular dysfunction. Whether MitoQ related improvements in arterial hemodynamics are a result of augmented cardiac function or a reduction in vascular resistance warrants future investigation in larger studies.

Following aerobic exercise, sustained vasodilation and concomitant reductions in total peripheral resistance (TPR) result in a reduction in blood pressure that is maintained for two or more hours. However, the time course for postexercise changes in reflected wave amplitude and other indices of pulsatile load on the left ventricle have not been thoroughly described. Therefore, we tested the hypothesis that reflected wave amplitude is reduced beyond an hour after cycling at 60% V̇O2peak for 60 min. Aortic pressure waveforms were derived in 14 healthy adults (7 men, 7 women; 26 ± 3 yr) from radial pulse waves acquired via high-fidelity applanation tonometry at baseline and every 20 min for 120 min postexercise. Concurrently, left ventricle outflow velocities were acquired via Doppler echocardiography and pressure-flow analyses were performed. Aortic characteristic impedance (Zc), forward (Pf) and backward (Pb) pulse wave amplitude, reflected wave travel time (RWTT), and wasted pressure effort were derived. Reductions in aortic blood pressure, Zc, Pf, and Pb were all sustained postexercise while increases in RWTT emerged from 60-100 min post exercise (all P<0.05). WPE was reduced by ~40% from 40-100 min post exercise (all P<0.02). Stepwise multiple regression analysis revealed that the peak ∆WPE was associated with ∆RWTT (β=-0.57, P=0.003) and ∆Pb (β=0.52, P=0.006), but not ∆cardiac output, ∆TPR, ∆Zc, or ∆Pf. These results suggest that changes in pulsatile hemodynamics are sustained for ≥100 min following moderate intensity aerobic exercise. Moreover, decreased and delayed reflected pressure waves are associated with decreased left ventricular wasted effort after exercise.

A significant proportion of patients with non-dialysis chronic kidney disease (CKD) present with mild-to-moderate deficits in the cognitive domains of executive function and episodic memory. Excess blood flow pulsatility is damaging to the microvasculature of high-flow, low-resistance organs like the brain and may contribute to the cognitive deficits prevalent among CKD patients. We tested the hypothesis that patients with moderate-to-severe non-dialysis CKD have excess flow pulsatility along their carotid and cerebral vasculature that is associated with deficits in executive function and episodic memory. We recruited 10 non-dialysis CKD patients (age=68±8 yrs; estimated glomerular filtration rate, eGFR=36±18 mL/min/1.73 m 2 ) and 7 healthy age-matched adults (age=65±5 yrs; eGFR=81±17 mL/min/1.73 m 2 ). Global cognitive function was assessed with the Montreal Cognitive Assessment (MoCA). Executive function and episodic memory were assessed using the NIH Toolbox Flanker Inhibitory Control and Attention Test and California Verbal Learning Test III, respectively, and reported as standardized scores (mean=100, SD=15). Pulsatility index [(systolic blood velocity - diastolic blood velocity)/ mean blood velocity] was measured in the common carotid (CCA), internal carotid (ICA), and middle cerebral arteries (MCA) via Doppler and transcranial Doppler ultrasound. Compared to healthy adults, CKD patients did not differ in total brain blood flow (p=0.42) but had lower MoCA (CKD=26±3, Healthy=29±1; p=0.01) and memory recall scores (CKD=92±21, Healthy=110±9; p=0.05). CKD patients did not differ from our healthy control group in executive function (CKD=91±10, Healthy=90±11; p=0.80) but did produce a mean score that was 0.6 SD lower than the NIH Toolbox reference sample. CKD patients had a higher pulsatility index in the CCA (CKD=2.3±0.5, Healthy=1.9±0.3; p=0.05) but not in the ICA (p=0.68) or MCA (p=0.57). CCA pulsatility index was strongly and inversely associated with episodic memory recall scores (r=-0.64, p<0.01, n=17). This data suggests that although the higher CCA flow pulsatility in non-dialysis CKD patients does not appear to be transmitted to the cerebrovasculature, it nevertheless may still be contributing to memory impairments.

In the hours following moderate intensity aerobic exercise (AE), persistent dilation of the arterial circulation supplying previously exercised muscle decreases total peripheral resistance (TPR) and contributes to post‐exercise hypotension. In addition to the effect of vasodilation on TPR, the diameter and tone of arterial vessels also influences central blood pressures via changes in the amplitude of forward (Pf) and backward (Pb) pulse waves, as well as the apparent wave reflection return timing (i.e. reflected wave transit time, RWTT). Prior research has assessed these parameters over a limited timeframe (e.g. 15 min) and relied on synthesized aortic flow waves rather than measured left ventricular outflow. As such, the prolonged post exercise effects of AE on pulse wave characteristics and central blood pressure are unclear. Purpose This study aimed to characterize changes in pulsatile hemodynamics in the two hours following AE. We hypothesized that Pf and Pb would be reduced, and RWTT would be increased post‐AE relative to baseline (BL). Methods Twelve young, recreationally active participants (8M/4F, 26±3 years, VO2max: 50.8±14.3 ml·kg−1·min−1) were studied at BL and then every 20 min after completing 60 min of upright cycling at 60% VO2max. At each timepoint, central pressure waveforms were derived from radial artery applanation tonometry and aortic inflow waves were acquired via echocardiographic pulsed‐Doppler assessment of blood velocity in the left ventricular outflow tract. Pressure and flow waves were averaged over 10 cardiac cycles and pressure‐flow relations were determined offline via wave separation analysis. Results As expected, brachial systolic blood pressure (SBP) was decreased across the 120 min period post‐AE relative to BL (time effect P<0.001) while TPR was only reduced at 20 min (Δ−15±5%, P<0.05 vs BL) and cardiac output (CO) was maintained at all timepoints (time effect P=0.12). The nadir in central SBP occurred at 60 min post‐AE (Δ−11±2%, P<0.001 vs BL). At 60 min post‐AE, Pf and Pb were reduced by Δ−14.3±2.5% and Δ−24.2±3.3%, respectively (each P<0.001 vs BL) and RWTT was increased (Δ19.5±5.3% P<0.02 vs BL). The percent change in central SBP from BL to 60 min was related to changes in RWTT (r=−0.79, P=0.02) and Pf (r=0.65, P=0.02) but not Pb (r=0.38, P=0.22), CO (r=0.27, P=0.40) or TPR (r=0.14, P=0.66). Conclusions These data highlight the contribution of changes in pulsatile hemodynamic parameters, in contrast to changes in non‐pulsatile parameters (CO and TPR), to reductions in central BP following moderate intensity AE. Support or Funding Information Supported by NIH grants R01‐HL104106 and P20‐GM113125