Wesley K. Lefferts

Effect of acute resistance exercise on carotid artery stiffness and cerebral blood flow pulsatility

Arterial stiffness is associated with cerebral flow pulsatility. Arterial stiffness increases following acute resistance exercise (RE). Whether this acute RE-induced vascular stiffening affects cerebral pulsatility remains unknown. Purpose: To investigate the effects of acute RE on common carotid artery (CCA) stiffness and cerebral blood flow velocity (CBFv) pulsatility. Methods: Eighteen healthy men (22 ± 1 yr; 23.7 ± 0.5 kg·m−2) underwent acute RE (5 sets, 5-RM bench press, 5 sets 10-RM bicep curls with 90 s rest intervals) or a time control condition (seated rest) in a randomized order. CCA stiffness (β-stiffness, Elastic Modulus (Ep)) and hemodynamics (pulsatility index, forward wave intensity, and reflected wave intensity) were assessed using a combination of Doppler ultrasound, wave intensity analysis and applanation tonometry at baseline and 3 times post-RE. CBFv pulsatility index was measured with transcranial Doppler at the middle cerebral artery (MCA). Results: CCA β-stiffness, Ep and CCA pulse pressure significantly increased post-RE and remained elevated throughout post-testing (p < 0.05). No changes in MCA or CCA pulsatility index were observed (p > 0.05). There were significant increases in forward wave intensity post-RE (p < 0.05) but not reflected wave intensity (p > 0.05). Conclusion: Although acute RE increases CCA stiffness and pressure pulsatility, it does not affect CCA or MCA flow pulsatility. Increases in pressure pulsatility may be due to increased forward wave intensity and not pressure from wave reflections.

Effect of acute nitrate supplementation on neurovascular coupling and cognitive performance in hypoxia

The matching of oxygen supply to neural demand (i.e., neurovascular coupling (NVC)) is an important determinant of cognitive performance. The impact of hypoxia on NVC remains poorly characterized. NVC is partially modulated by nitric oxide (NO), which may initially decrease in hypoxia. This study investigated the effect of acute NO-donor (nitrate) supplementation on NVC and cognitive function in hypoxia. Twenty healthy men participated in this randomized, double-blind, crossover design study. Following normoxic cognitive/NVC testing, participants consumed either nitrate (NIT) or a NIT-depleted placebo (PLA). Participants then underwent 120 min of hypoxia (11.6% ± 0.1% O2) and all cognitive/NVC testing was repeated. NVC was assessed as change in middle cerebral artery (MCA) blood flow during a cognitive task (incongruent Stroop) using transcranial Doppler. Additional computerized cognitive testing was conducted separately to assess memory, executive function, attention, sensorimotor, and social cognition domains. Salivary nitrite significantly increased following supplementation in hypoxia for NIT (+2.6 ± 1.0 arbitrary units (AU)) compared with PLA (+0.2 ± 0.3 AU; p < 0.05). Memory performance (-6 ± 13 correct) significantly decreased (p < 0.05) in hypoxia while all other cognitive domains were unchanged in hypoxia for both PLA and NIT conditions (p > 0.05). MCA flow increased during Stroop similarly in normoxia (PLA +5 ± 6 cm·s(-1), NIT +7 ± 7 cm·s(-1)) and hypoxia (PLA +5 ± 9 cm·s(-1), NIT +6 ± 7 cm·s(-1)) (p < 0.05) and this increase was not altered by PLA or NIT (p > 0.05). In conclusion, acute hypoxia resulted in significant reductions in memory concomitant with preservation of executive function, attention, and sensorimotor function. Hypoxia had no effect on NVC. Acute NIT supplementation had no effect on NVC or cognitive performance in hypoxia.

Manipulation of arterial stiffness, wave reflections, and retrograde shear rate in the femoral artery using lower limb external compression

Exposure of the arterial wall to retrograde shear acutely leads to endothelial dysfunction and chronically contributes to a proatherogenic vascular phenotype. Arterial stiffness and increased pressure from wave reflections are known arbiters of blood flow in the systemic circulation and each related to atherosclerosis. Using distal external compression of the calf to increase upstream retrograde shear in the superficial femoral artery (SFA), we examined the hypothesis that changes in retrograde shear are correlated with changes in SFA stiffness and pressure from wave reflections. For this purpose, a pneumatic cuff was applied to the calf and inflated to 0, 35, and 70 mmHg (5 min compression, randomized order, separated by 5 min) in 16 healthy young men (23 ± 1 years of age). Doppler ultrasound and wave intensity analysis was used to measure SFA retrograde shear rate, reflected pressure wave intensity (negative area [NA]), elastic modulus (Ep), and a single‐point pulse wave velocity (PWV) during acute cuff inflation. Cuff inflation resulted in stepwise increases in retrograde shear rate (P < 0.05 for main effect). There were also significant cuff pressure‐dependent increases in NA, Ep, and PWV across conditions (P < 0.05 for main effects). Change in NA, but not Ep or PWV, was associated with change in retrograde shear rate across conditions (P < 0.05). In conclusion, external compression of the calf increases retrograde shear, arterial stiffness, and pressure from wave reflection in the upstream SFA in a dose‐dependent manner. Wave reflection intensity, but not arterial stiffness, is correlated with changes in peripheral retrograde shear with this hemodynamic manipulation.

Hemodynamic Correlates of Late Systolic Flow Velocity Augmentation in the Carotid Artery

Background. The contour of the common carotid artery (CCA) blood flow velocity waveform changes with age; CCA flow velocity increases during late systole, and this may contribute to cerebrovascular disease. Late systolic flow velocity augmentation can be quantified using the flow augmentation index (FAIx). We examined hemodynamic correlates of FAIx to gain insight into determinants of CCA flow patterns. Methods. CCA Doppler ultrasound and wave intensity analysis (WIA) were used to assess regional hemodynamics in 18 young healthy men (age 22 ± 1 years). Forward waves (W 1) and backward waves (negative area, NA) were measured and used to calculate the reflection index (NA/W 1 = RIx). Additional parameters included W 2 which is a forward travelling expansion/decompression wave of myocardial origin that produces suction, CCA single-point pulse wave velocity (PWV) as a measure of arterial stiffness, and CCA pressure augmentation index (AIx). Results. Primary correlates of FAIx included W 2 (r = − 0.52, P < 0.05), logRIx (r = 0.56, P < 0.05), and AIx (r = 0.60, P < 0.05). FAIx was not associated with CCA stiffness (P > 0.05). Conclusions. FAIx is a complex ventricular-vascular coupling parameter that is associated with both increased expansion wave magnitude (increased suction from the left ventricle) and increased pressure from wave reflections.

Firefighter's personal protective equipment and the chronotropic index.

The purpose of this study was to investigate the effects of personal protective equipment (PPE) on cardiovascular and metabolic responses during incremental exercise, and to determine if PPE affects the relationship between heart rate (HR) and oxygen uptake when expressed as the chronotropic index (CI). Ten male participants performed graded exercise tests under three conditions: control (CON), (PPE) and weighted vest (WV) (same weight as PPE). Time to exhaustion was significantly longer in the CON compared to the other conditions (p < 0.01). Submaximal oxygen uptake and HR were significantly lower in the CON compared to the PPE and WV conditions. The CI (CON, 32.2 ± 4.5; PPE, 31.7 ± 5.7; WV, 32.6 ± 4.9) was similar in all three conditions. This study has shown that additional weight and encapsulating clothing leads to elevations in HR and oxygen uptake compared to a control condition, however, the CI remains unaffected. Practitioner Summary: Firefighters wear personal protective equipment that is designed to protect the wearer; however it also imposes a physiological burden. It is known that work in firefighting PPE increases cardiovascular and metabolic strain. This study has shown that PPE does not alter the relationship between heart rate and oxygen uptake.

Vascular and central hemodynamic changes following exercise-induced heat stress.

This study examined the effects of moderate exercise-induced heat stress (EIHS) on vascular function, central hemodynamic load and indices of coronary perfusion. Vascular-hemodynamic measures were collected in 12 healthy men (aged 22±3 years) pre and post 100 minutes of moderate, intermittent exercise in two randomized conditions: heat stress (HS; wearing firefighter personal protective equipment (PPE)), and no heat stress (NHS; wearing a cooling shirt and equivalent PPE weight). Aortic blood pressure, reflected wave pressure (Pb), systolic (SPTI) and diastolic pressure time-integral (DPTI), and aortic stiffness were assessed before and after each condition. SPTI was significantly greater, and DPTI and Pb were significantly lower for HS-post compared to NHS-post (p<0.05). Pulse wave velocity was not different between conditions. In conclusion, EIHS does not affect aortic stiffness, but increases indices of myocardial work and reduces indices of coronary perfusion which may be related to chronotropic responses to EIHS. The mismatch between oxygen demand and oxygen supply may increase cardiac vulnerability to ischemia during strenuous work in the heat.

Effect of Clothing Layers in Combination with Fire Fighting Personal Protective Clothing on Physiological and Perceptual Responses to Intermittent Work and on Materials Performance Test Results

Personal protective clothing (PPC) shields firefighters from thermal and other occupational hazards; however, it also contributes to physiological and perceptual strain. This study examined the effect of clothing layers worn under structural fire fighting turnout gear (TOG) on physiological and perceptual responses during alternating work/recovery cycles and assessed the clothing ensembles’ (PPC + base layer) material performance. Values are reported as mean ± standard error of the mean. Ten men (age, 21 ± 0.3 yr; height, 1.74 ± 0.02 m; weight, 74.3 ± 2.3 kg; VO2max, 58.9 ± 2.0 mL/kg/min) completed a 110-min alternating work/recovery walking protocol (three 20-min exercise bouts/10-, 20-, and 20-min recovery sessions) in a thermo-neutral (21.0°C, 58.7% RH) laboratory while wearing a cotton t-shirt (COT) or COT and a station uniform (SU) shirt under fire fighting TOG (COT+TOG and COT+SU+TOG, respectively). Changes in heart rate (HR), core temperature (Tco), skin temperature (Tsk), rating of perceived exertion (RPE), and thermal sensations (TS) were compared across exercise and recovery periods. During exercise sessions, HR, Tco, Tsk, and RPE reached similar levels for COT+TOG and COT+SU+TOG. During Recoveries 1, 2, and 3, mean chest Tsk decreased by 3.96, 6.64, and 6.49°C, respectively, for COT+TOG compared with 2.24, 3.78, and 4.09°C for COT+SU+TOG (p < 0.05 for each period). Change in TS differed during Exercise 1; however, mean peak TS corresponded to “hot” for both ensembles. This study demonstrates that the additional layer of clothing in the COT+SU+TOG ensemble imposed no greater level of physiological or perceptual strain during moderate-intensity work bouts compared with the COT+TOG ensemble. However, some modest benefits were experienced during the recovery sessions for the COT+TOG ensemble as evidenced by a lower chest Tsk. In addition, materials performance testing revealed COT+SU+TOG provided greater thermal protection (64.8 ± 1.9 vs. 56.4 ± 0.3 cal/cm2; p < 0.05) and equivalent heat dissipation compared with COT+TOG. These findings could guide departmental decisions about the use of station shirts.

Self-Reported Sitting Time Is Associated With Higher Pressure From Wave Reflections Independent of Physical Activity Levels in Healthy Young Adults

BACKGROUND Time spent in sedentary pursuits such as sitting (SIT) is associated with an increased risk of cardiovascular disease independent of physical activity (PA). The purpose of this study was to examine the associations of PA and SIT with central hemodynamic burden in young adults. METHODS Aortic pressure waveforms were obtained using radial applanation tonometry and a generalized transfer function in 70 young healthy men (n = 41) and women (n = 29) (mean age = 23±1 years; body mass index = 24±1kg/m(2)). A wave separation technique that uses a physiologic pseudoaortic flow waveform was used to derive incident/forward wave pressure (Pf) and reflected/backward wave pressure (Pb). Levels of PA (metabolic equivalent, minutes per week) and SIT (sitting time per day) were obtained by self-report using the International Physical Activity Questionnaire. RESULTS A negative correlation existed between PA and Pf (r = -0.30; P < 0.05) and Pb (r = -0.36; P < 0.05). A positive correlation existed between SIT and Pf (r = 0.39; P < 0.05) and Pb (r = 0.44; P < 0.05). According to results from multiple regression, after adjusting for potential confounders (age, sex, height, heart rate, mean pressure) and PA, associations between SIT and Pf (P < 0.05) and SIT and Pb (P < 0.05) remained. CONCLUSIONS SIT is associated with higher forward wave pressure and backward wave pressure, 2 novel hemodynamic correlates of cardiovascular disease risk and target organ damage, in young apparently healthy men and women. This association is independent of PA.

Effect of Hypoxia on Cerebrovascular and Cognitive Function during Moderate Intensity Exercise

Exercise in hypoxia places added demands on the brain and cerebrovasculature that can impact cognitive function. The purpose of this study was to investigate the effect of acute hypoxia on cerebrovascular hemodynamics, markers of neuro-steroidal modulation and brain-blood barrier (BBB) integrity, and cognition during exercise. Thirty healthy participants (21±4yrs., BMI 24.0±2.6kg∙m(-2); 15 men) were randomized to both a≈2.5h normoxic (FiO2 20.0%) and hypoxic (FiO2 12.5%) condition on two separate days. After 1.25h, participants underwent 10min of exercise-alone (cycling at 55% HRmax) and 15min of exercise+cognitive testing. Prefrontal cortex (PFC) tissue oxygenation and middle cerebral artery (MCA) mean blood velocity (MnV) were measured using near-infrared spectroscopy and transcranial Doppler respectively at rest, during exercise-alone, and during exercise+cognitive testing. Salivary levels of dehydroepiandosterone [DHEA], DHEA-sulfate [DHEAS]) and neuron specific enolase (NSE) were measured pre and post exercise. Cognition was assessed using standard metrics of accuracy and reaction time (RT), and advanced metrics from drift-diffusion modeling across memory recognition, N-Back and Flanker tasks. MCA MnV increased from rest to exercise (p<0.01) and was unchanged with addition of cognitive testing during exercise in both normoxia and hypoxia. PFC oxygenation increased during exercise (p<0.05) and was further increased with addition of cognitive challenge in normoxia but decreased during exercise in hypoxia (p<0.05) with further reductions occurring with addition of cognitive tasks (p<0.05). DHEA and NSE increased and decreased post-exercise, respectively, in both normoxia and hypoxia (p<0.01). Accuracy on cognitive tasks was similar in normoxia compared to hypoxia, while RT was slower in hypoxia vs normoxia across memory recognition (p<0.01) and Flanker tasks (p=0.04). Drift-diffusion modeling suggested changes in memory RT were due to increases in caution (p<0.01). Overall cognitive performance is maintained during exercise in hypoxia concomitant with slower RT in select cognitive tasks and reduced oxygenation in the PFC. These changes were accompanied by slight increases in neuro-steroidal modulation but appear independent of changes in NSE, a biomarker of BBB integrity. Maintained accuracy and select increases in RT during hypoxic exercise may be related behavioral changes in caution.

Effect of acute nitrate ingestion on central hemodynamic load in hypoxia

UNLABELLED Acute hypoxia results in local vasodilation that may temporarily unload the left ventricle (LV) through nitric oxide (NO)-mediated mechanisms. Whether increasing NO levels augments LV unloading and improves ventricular-vascular coupling in hypoxia remains unknown. PURPOSE Investigate the effect of acute nitrate ingestion on central hemodynamic load in hypoxia. METHODS 20 Healthy men (23 ± 3 yrs, BMI 24.6 ± 2.8 kg m(-2)) consumed 70 mL of either a) 0.45 g nitrate (NIT) or b) an inert placebo (PLA) prior to 105 min of normobaric hypoxia (11.6 ± 0.1%) in this randomized, double-blind, crossover-design study. Wave reflection index (RIX; ratio of forward to reflected wave pressure), augmentation index (AIX75) and pulse wave velocity were calculated as measures of wave reflection magnitude and aortic stiffness, respectively, from the aortic blood pressure (BP) waveform. LV wasted pressure effort (WPE) was calculated as an index of LV work due to wave reflections. Subendocardial viability ratio (SEVR) was assessed a measure of myocardial O2 supply/demand ratio. RESULTS Aortic diastolic BP decreased in hypoxia compared to normoxia (p < 0.05). Aortic RIX, AIX75, and LV WPE significantly decreased in hypoxia compared to normoxia (p < 0.05). Aortic systolic BP, SEVR, and PWV were unaffected by hypoxia (p > 0.05). Compared to placebo, nitrate ingestion did not significantly alter central hemodynamics in hypoxia (p > 0.05). CONCLUSIONS Acute hypoxic exposure unloads the LV (WPE, AIX75, and RIX) without disturbing myocardial O2 supply-demand ratio (SEVR). Reductions in LV work with hypoxia are likely due to reductions in pressure from wave reflections as hypoxia had negligible effects on aortic stiffness. Nitrate ingestion did not affect the central hemodynamic response to acute systemic hypoxia.