Cool head-out water immersion does not alter cerebrovascular reactivity to hypercapnia despite elevated middle cerebral artery blood velocity: A pilot study.

Episodic increases in cerebral blood flow (CBF) are thought to contribute to improved cerebrovascular function and health. Head-out water immersion (HOWI) may be a useful modality to increase CBF secondary to the hydrostatic pressure placed on the body. However, it is unclear whether water temperatures common to the general public elicit similar cerebrovascular responses. We tested the hypothesis that mean middle cerebral artery blood velocity (MCAvmean) and cerebrovascular reactivity to CO2 (CVRCO2) would be higher during an acute bout of thermoneutral (TN; 35°C) vs. cool (COOL; 25°C) HOWI. Ten healthy participants (age: 23±3 y; 4 women) completed two randomized HOWI visits. Right MCAvmean, end-tidal CO2 (PETCO2) mean arterial pressure (MAP), and MCA conductance (MCAvmean/MAP) were continuously recorded. CVRCO2 was assessed using a stepped hypercapnia protocol before (PRE), at 30 minutes of HOWI (HOWI), immediately after HOWI (POST-1), and 45 minutes after HOWI (POST-2). Absolute values are reported as mean ± SD. MCAvmean, PETCO2, MAP, and CVRCO2 were not different between conditions at any timepoint (all P≥0.17). In COOL, MCAvmean increased from PRE (61±9 cm/s) during HOWI (68±11 cm/s), at POST-1 (69±11 cm/s), and POST-2 (72±8 cm/s) (all P<0.01), and in TN from PRE to POST-1 (66±13 vs. 71±14 cm/s; P = 0.05). PETCO2 did not change over time in either condition. In COOL, MAP increased from PRE (85±5 mmHg) during HOWI (101±4 mmHg), at POST-1 (97±7 mmHg), and POST-2 (96±9 mmHg), and in TN from PRE (88±5 mmHg) at HOWI (98±7 mmHg) and POST-1 (99±8 mmHg) (all P<0.01). In COOL, CVRCO2 increased from PRE to HOWI (1.66±0.55 vs. 1.92±0.52 cm/s/mmHg; P = 0.04). MCA conductance was not different between or within conditions. These data indicate that 30 minutes of cool HOWI augments MCAvmean and that the increase in MCAvmean persists beyond cool HOWI. However, cool HOWI does not alter CVRCO2 in healthy young adults.

Renal vascular control during normothermia and passive heat stress does not differ between healthy younger men and women.

Men are likely at greater risk for heat-induced acute kidney injury compared with women, possibly due to differences in vascular control. We tested the hypothesis that the renal vasoconstrictor and vasodilator responses will be greater in younger women compared with men during passive heat stress. Twenty-five healthy adults [12 women (early follicular phase) and 13 men] completed two experimental visits, heat stress or normothermic time-control, assigned in a block-randomized crossover design. During heat stress, participants wore a water-perfused suit perfused with 50°C water. Core temperature was increased by ∼0.8°C in the first hour before commencing a 2-min cold pressor test (CPT). Core temperature remained clamped and at 1-h post-CPT, subjects ingested a whey protein shake (1.2 g of protein/kg body wt), and measurements were taken pre-, 75 min, and 150 min post-protein. Beat-to-beat blood pressure (Penaz method) was measured and segmental artery vascular resistance (VR, Doppler ultrasound) was calculated as segmental artery blood velocity ÷ mean arterial pressure. CPT-induced increases in segmental artery VR did not differ between trials (trial effect: P = 0.142) nor between men (heat stress: 1.5 ± 1.0 mmHg/cm/s, normothermia: 1.4 ± 1.0 mmHg/cm/s) and women (heat stress: 1.4 ± 1.2 mmHg/cm/s, normothermia: 2.1 ± 1.1 mmHg/cm/s) (group effect: P = 0.429). Reductions in segmental artery VR following oral protein loading did not differ between trials (trial effect: P = 0.080) nor between men (heat stress: -0.6 ± 0.8 mmHg/cm/s, normothermia: -0.6 ± 0.6 mmHg/cm/s) and women (heat stress: -0.5 ± 0.5 mmHg/cm/s, normothermia: -1.1 ± 0.6 mmHg/cm/s) (group effect: P = 0.204). Renal vasoconstrictor responses to the cold pressor test and vasodilator responses following an oral protein load during heat stress or normothermia do not differ between younger men and younger women in the early follicular phase of the menstrual cycle.NEW & NOTEWORTHY The mechanisms underlying greater heat-induced acute kidney injury risk in men versus women remain unknown. This study examined renal vascular control, including both vasodilatory (oral protein load) and vasoconstrictor (cold presser test) responses, during normothermia and heat stress and compared these responses between men and women. The results indicated that in both conditions neither renal vasodilatory nor vasoconstrictor responses differ between younger men and younger women.

Elevations in sweat sodium concentration following ischemia-reperfusion injury during passive heat stress.

Renal ischemia-reperfusion (I/R) injury results in damage to the renal tubules and causes impairments in sodium [Na+] reabsorption. Given the inability to conduct mechanistic renal I/R injury studies in vivo in humans, eccrine sweat glands have been proposed as a surrogate model given the anatomical and physiological similarities. We tested the hypothesis that sweat Na+ concentration is elevated following I/R injury during passive heat stress. We also tested the hypothesis that I/R injury during heat stress will impair cutaneous microvascular function. Fifteen young healthy adults completed ∼160 min of passive heat stress using a water-perfused suit (50°C). At 60 min of whole body heating, one upper arm was occluded for 20 min followed by a 20-min reperfusion. Sweat was collected from each forearm via an absorbent patch pre- and post-I/R. Following the 20-min reperfusion, cutaneous microvascular function was measured via local heating protocol. Cutaneous vascular conductance (CVC) was calculated as red blood cell flux/mean arterial pressure and normalized to CVC during local heating to 44°C. Na+ concentration was log-transformed and data were reported as a mean change from pre-I/R (95% confidence interval). Changes in sweat sodium concentration from pre-I/R differed between arms post-I/R (experimental arm: +0.97 [+0.67 - 1.27] [LOG] Na+; control arm: +0.68 [+0.38 - 0.99] [LOG] Na+; P < 0.01). However, CVC during the local heating was not different between the experimental (80 ± 10%max) and control arms (78 ± 10%max; P = 0.59). In support of our hypothesis, Na+ concentration was elevated following I/R injury, but likely not accompanied by alterations in cutaneous microvascular function.NEW & NOTEWORTHY In the present study, we have demonstrated that sweat sodium concentration is elevated following ischemia-reperfusion injury during passive heat stress. This does not appear to be mediated by reductions in cutaneous microvascular function or active sweat glands, but may be related to alterations in local sweating responses during heat stress. This study demonstrates a potential use of eccrine sweat glands to understand sodium handling following ischemia-reperfusion injury, particularly given the challenges of in vivo studies of renal ischemia-reperfusion injury in humans.

Acute beetroot juice consumption does not alter cerebral autoregulation or cardiovagal baroreflex sensitivity during lower-body negative pressure in healthy adults.

Introduction: Beetroot juice (BRJ) improves peripheral endothelial function and vascular compliance, likely due to increased nitric oxide bioavailability. It is unknown if BRJ alters cerebrovascular function and cardiovagal baroreflex control in healthy individuals. Purpose: We tested the hypotheses that BRJ consumption improves cerebral autoregulation (CA) and cardiovagal baroreflex sensitivity (cBRS) during lower-body negative pressure (LBNP). Methods: Thirteen healthy adults (age: 26 ± 4 years; 5 women) performed oscillatory (O-LBNP) and static LBNP (S-LBNP) before (PRE) and 3 h after consuming 500 mL of BRJ (POST). Participants inhaled 3% CO2 (21% O2, 76% N2) during a 5 min baseline and throughout LBNP to attenuate reductions in end-tidal CO2 tension (PETCO2). O-LBNP was conducted at ∼0.02 Hz for six cycles (-70 mmHg), followed by a 3-min recovery before S-LBNP (-40 mmHg) for 7 min. Beat-to-beat middle cerebral artery blood velocity (MCAv) (transcranial Doppler) and blood pressure were continuously recorded. CA was assessed using transfer function analysis to calculate coherence, gain, and phase in the very-low-frequency (VLF; 0.020-0.070 Hz) and low-frequency bands (LF; 0.07-0.20 Hz). cBRS was calculated using the sequence method. Comparisons between POST vs. PRE are reported as mean ± SD. Results: During O-LBNP, coherence VLF was greater at POST (0.55 ± 0.06 vs. 0.46 ± 0.08; P < 0.01), but phase VLF (P = 0.17) and gain VLF (P = 0.69) were not different. Coherence LF and phase LF were not different, but gain LF was lower at POST (1.03 ± 0.20 vs. 1.12 ± 0.30 cm/s/mmHg; P = 0.05). During S-LBNP, CA was not different in the VLF or LF bands (all P > 0.10). Up-cBRS and Down-cBRS were not different during both LBNP protocols. Conclusion: These preliminary data indicate that CA and cBRS during LBNP in healthy, young adults is largely unaffected by an acute bolus of BRJ.

Glomerular filtration rate reserve is reduced during mild passive heat stress in healthy young adults.

We tested the hypothesis that, compared with normothermia, the increase in glomerular filtration rate (GFR) after an oral protein load (defined as the GFR reserve) is attenuated during moderate passive heat stress in young healthy adults. Sixteen participants (5 women; 26 ± 2 yr) completed two experimental visits, heat stress or a normothermic time-control, assigned in a block-randomized crossover design. During the heat stress trial, core temperature was increased by 0.6°C in the first hour before commencing a 2-min cold pressor test (CPT) to assess renal vasoconstrictor responses. One-hour post-CPT, subjects ingested a whey protein shake (1.2 g of protein/kg body wt), and measurements were taken pre-, 75, and 150 min postprotein. Segmental artery vascular resistance was calculated as the quotient of Doppler ultrasound-derived segmental artery blood velocity and mean arterial pressure and provided an estimate of renal vascular tone. GFR was estimated from creatinine clearance. The increase in segmental artery vascular resistance during the CPT was attenuated during heat stress (end CPT: 5.6 ± 0.9 vs. 4.7 ± 1.1 mmHg/cm/s, P = 0.024). However, the reduction in segmental artery vascular resistance in response to an oral protein load did not differ between heat stress (at 150 min: 1.9 ± 0.4 mmHg/cm/s) and normothermia (at 150 min: 1.8 ± 0.5 mmHg/cm/s; P = 0.979). The peak increase in creatinine clearance postprotein, independent of time, was attenuated during heat stress (+26 ± 19 vs. +16 ± 20 mL/min, P = 0.013, n = 13). GFR reserve is diminished by mild passive heat stress. Moreover, renal vasoconstrictor responses are attenuated by mild passive heat stress, but renal vasodilator responses are maintained.

Cerebral vascular function following the acute consumption of caffeinated artificially- and sugar sweetened soft drinks in healthy adults.

Chronic consumption of sugar- and artificially-sweetened beverages (SSB and ASB) are associated with an increased risk of stroke but it is unclear how acute consumption influences cerebral vascular function. Purpose: We hypothesized that: (1) acute consumption of SSB and ASB would augment dynamic cerebral autoregulation (dCA) and attenuate cerebral vascular reactivity to hypercapnia (CVRCO2) compared to water; and (2) dCA and CVRCO2 would be attenuated with SSB compared to ASB and water. Methods: Twelve healthy adults (age: 23 ± 2 years, four females) completed three randomized trials where they drank 500 ml of water, SSB (Mountain Dew®), or ASB (Diet Mountain Dew®). We measured mean arterial pressure (MAP), middle and posterior cerebral artery blood velocities (MCAv and PCAv), and end-tidal CO2 tension (PETCO2). Cerebral vascular conductance was calculated as cerebral artery blood velocity/MAP (MCAc and PCAc). Twenty min after consumption, participants completed a 5 min baseline, and in a counterbalanced order, a CVRCO2 test (3%, 5%, and 7% CO2 in 3 min stages) and a dCA test (squat-stand tests at 0.10 Hz and 0.05 Hz for 5 min each) separated by 10 min. CVRCO2 was calculated as the slope of the linear regression lines of MCAv and PCAv vs. PETCO2. dCA was assessed in the MCA using transfer function analysis. Coherence, gain, and phase were determined in the low frequency (LF; 0.07-0.2 Hz) and very low frequency (VLF; 0.02-0.07 Hz). Results: MCAv and MCAc were lower after SSB (54.11 ± 12.28 cm/s, 0.58 ± 0.15 cm/s/mmHg) and ASB (51.07 ± 9.35 cm/s, 0.52 ± 1.0 cm/s/mmHg) vs. water (62.73 ± 12.96 cm/s, 0.67 ± 0.11 cm/s/mmHg; all P < 0.035), respectively. PCAc was also lower with the ASB compared to water (P = 0.007). MCA CVRCO2 was lower following ASB (1.55 ± 0.38 cm/s/mmHg) vs. water (2.00 ± 0.57 cm/s/mmHg; P = 0.011) but not after SSB (1.90 ± 0.67 cm/s/mmHg; P = 0.593). PCA CVRCO2 did not differ between beverages (P > 0.853). There were no differences between beverages for coherence (P ≥ 0.295), gain (P ≥ 0.058), or phase (P ≥ 0.084) for either frequency. Discussion: Acute consumption of caffeinated SSB and ASB resulted in lower intracranial artery blood velocity and conductance but had a minimal effect on cerebral vascular function as only MCA CVRCO2 was altered with the ASB compared to water.

Hot head-out water immersion does not acutely alter dynamic cerebral autoregulation or cerebrovascular reactivity to hypercapnia.

Recurring hot head-out water immersion (HOWI) enhances peripheral vascular function and cerebral blood velocity during non-immersion conditions. However, it is unknown if an acute bout of hot HOWI alters cerebrovascular function. Using two experimental studies, we tested the hypotheses that dynamic cerebral autoregulation (dCA) and cerebrovascular reactivity (CVR) are improved during an acute bout of hot (HOT; 39 °C) vs. thermoneutral (TN; 35 °C) HOWI. Eighteen healthy participants (eight females) completed the dCA study, and 14 participants (6 females) completed the CVR study. Both studies consisted of two randomized (TNdCA vs. HOTdCA; TNCVR vs. HOTCVR) 45minute HOWI visits. Middle cerebral artery blood velocity (MCAvmean) was continuously recorded. dCA was assessed using a respiratory impedance device and analyzed via transfer gain and phase in the low-frequency band. CVR was assessed using stepped hypercapnia. Assessments were completed PRE and 30 minutes into HOWI. Values are reported as a change (Δ) from PRE (mean ± SD). There were no differences at PRE for either study. ΔMCAvmean was greater in TNdCA (TNdCA: 4 ± 4 vs. HOTdCA: -3 ± 5 cm/s; P < 0.01) and TNCVR (TNCVR: 5 ± 4 vs. HOTCVR: -1 ± 6 cm/s; P < 0.01) during HOWI. ΔGain was greater in HOTdCA during HOWI (TNdCA: -0.09 ± 0.15 vs. HOTdCA: 0.10 ± 0.17 cm/s/mmHg; P = 0.04). ΔPhase (P > 0.84) and ΔCVR (P > 0.94) were not different between conditions. These data indicate that hot and thermoneutral water immersion do not acutely alter cerebrovascular function in healthy, young adults.

Acute Beetroot Juice Ingestion Does Not Alter Renal Hemodynamics during Normoxia and Mild Hypercapnia in Healthy Young Adults.

Arterial hypercapnia reduces renal perfusion. Beetroot juice (BRJ) increases nitric oxide bioavailability and may improve renal blood flow. We tested the hypothesis that acute consumption of BRJ attenuates both decreases in blood velocity and increases in vascular resistance in the renal and segmental arteries during acute hypercapnia. In fourteen healthy young adults, blood velocity and vascular resistance were measured with Doppler ultrasound in the renal and segmental arteries during five minutes of breathing a carbon dioxide gas mixture (CO2) before and three hours after consuming 500 mL of BRJ. There was no difference between pre- and post-BRJ consumption in the increase in the partial pressure of end-tidal CO2 during CO2 breathing (pre: +4 ± 1 mmHg; post: +4 ± 2 mmHg, p = 0.4281). Segmental artery blood velocity decreased during CO2 breathing in both pre- (by -1.8 ± 1.9 cm/s, p = 0.0193) and post-BRJ (by -2.1 ± 1.9 cm/s, p = 0.0079), but there were no differences between pre- and post-consumption (p = 0.7633). Segmental artery vascular resistance increased from room air baseline during CO2 at pre-BRJ consumption (by 0.4 ± 0.4 mmHg/cm/s, p = 0.0153) but not post-BRJ (p = 0.1336), with no differences between pre- and post-consumption (p = 0.7407). These findings indicate that BRJ consumption does not attenuate reductions in renal perfusion during acute mild hypercapnia in healthy young adults.

Preliminary Evidence of Orthostatic Intolerance and Altered Cerebral Vascular Control Following Sport-Related Concussion.

Concussions have been shown to result in autonomic dysfunction and altered cerebral vascular function. We tested the hypothesis that concussed athletes (CA) would have altered cerebral vascular function during acute decreases and increases in blood pressure compared to healthy controls (HC). Ten CA (age: 20 ± 2 y, 7 females) and 10 HC (age: 21 ± 2 y, 6 females) completed 5 min of lower body negative pressure (LBNP; -40 mmHg) and 5 min of lower body positive pressure (LBPP; 20 mmHg). Protocols were randomized and separated by 10 min. Mean arterial pressure (MAP) and middle cerebral artery blood velocity (MCAv) were continuously recorded. Cerebral vascular resistance (CVR) was calculated as MAP/MCAv. Values are reported as change from baseline to the last minute achieved (LBNP) or 5 min (LBPP). There were no differences in baseline values between groups. During LBNP, there were no differences in the change for MAP (CA: -23 ± 18 vs. HC: -21 ± 17 cm/s; P = 0.80) or MCAv (CA: -13 ± 8 vs. HC: -18 ± 9 cm/s; P = 0.19). The change in CVR was different between groups (CA: -0.08 ± 0.26 vs. HC: 0.18 ± 0.24 mmHg/cm/s; P = 0.04). Total LBNP time was lower for CA (204 ± 92 s) vs. HC (297 ± 64 s; P = 0.04). During LBPP, the change in MAP was not different between groups (CA: 13 ± 6 vs. HC: 10 ± 7 mmHg; P = 0.32). The change in MCAv (CA: 7 ± 6 vs. HC: -4 ± 13 cm/s; P = 0.04) and CVR (CA: -0.06 ± 0.27 vs. HC: 0.38 ± 0.41 mmHg/cm/s; P = 0.03) were different between groups. CA exhibited impaired tolerance to LBNP and had a different cerebral vascular response to LBPP compared to HC.

Sugar-sweetened soft drink consumption acutely decreases spontaneous baroreflex sensitivity and heart rate variability.

In healthy humans, fructose-sweetened water consumption increases blood pressure variability (BPV) and decreases spontaneous cardiovagal baroreflex sensitivity (cBRS) and heart rate variability (HRV). However, whether consuming commercially available soft drinks containing high levels of fructose elicits similar responses is unknown. We hypothesized that high-fructose corn syrup (HFCS)-sweetened soft drink consumption increases BPV and decreases cBRS and HRV to a greater extent compared with artificially sweetened (diet) and sucrose-sweetened (sucrose) soft drinks and water. Twelve subjects completed four randomized, double-blinded trials in which they drank 500 mL of water or commercially available soft drinks matched for taste and caffeine content. We continuously measured beat-to-beat blood pressure (photoplethysmography) and R-R interval (ECG) before and 30 min after drink consumption during supine rest for 5 min during spontaneous and paced breathing. BPV was evaluated using standard deviation (SD), average real variability (ARV), and successive variation (SV) methods for systolic and diastolic blood pressure. cBRS was assessed using the sequence method. HRV was evaluated using the root mean square of successive differences (RMSSD) in R-R interval. There were no differences between conditions in the magnitude of change from baseline in SD, ARV, and SV (P ≥ 0.07). There were greater reductions in cBRS during spontaneous breathing in the HFCS (-3 ± 5 ms/mmHg) and sucrose (-3 ± 5 ms/mmHg) trials compared with the water trial (+1 ± 5 ms/mmHg, P < 0.03). During paced breathing, HFCS evoked greater reductions in RMSSD compared with water (-26 ± 34 vs. +2 ± 26 ms, P < 0.01). These findings suggest that sugar-sweetened soft drink consumption alters cBRS and HRV but not BPV.

Renal and segmental artery hemodynamic response to acute, mild hypercapnia.

Profound increases (>15 mmHg) in arterial carbon dioxide (i.e., hypercapnia) reduce renal blood flow. However, a relatively brief and mild hypercapnia can occur in patients with sleep apnea or in those receiving supplemental oxygen therapy during an acute exacerbation of chronic obstructive pulmonary disease. We tested the hypothesis that a brief, mild hypercapnic exposure increases vascular resistance in the renal and segmental arteries. Blood velocity in 14 healthy adults (26 ± 4 yr; 7 women, 7 men) was measured in the renal and segmental arteries with Doppler ultrasound while subjects breathed room air (Air) and while they breathed a 3% CO2, 21% O2, 76% N2 gas mixture for 5 min (CO2). The end-tidal partial pressure of CO2 ([Formula: see text]) was measured via capnography. Mean arterial pressure (MAP) was measured beat to beat via the Penaz method. Vascular resistance in the renal and segmental arteries was calculated as MAP divided by blood velocity. [Formula: see text] increased with CO2 (Air: 45 ± 3, CO2: 48 ± 3 mmHg, P < 0.01), but there were no changes in MAP (P = 0.77). CO2 decreased blood velocity in the renal (Air: 35.2 ± 8.1, CO2: 32.2 ± 7.3 cm/s, P < 0.01) and segmental (Air: 24.2 ± 5.1, CO2: 21.8 ± 4.2 cm/s, P < 0.01) arteries and increased vascular resistance in the renal (Air: 2.7 ± 0.9, CO2: 3.0 ± 0.9 mmHg·cm-1·s, P < 0.01) and segmental (Air: 3.9 ± 1.0, CO2: 4.4 ± 1.0 mmHg·cm-1·s, P < 0.01) arteries. These data provide evidence that the kidneys are hemodynamically responsive to a mild and acute hypercapnic stimulus in healthy humans.