Robert T. Davis

Spaceflight-induced alterations in cerebral artery vasoconstrictor, mechanical, and structural properties: implications for elevated cerebral perfusion and intracranial pressure

Evidence indicates that cerebral blood flow is both increased and diminished in astronauts on return to Earth. Data from ground‐based animal models simulating the effects of microgravity have shown that decrements in cerebral perfusion are associated with enhanced vasoconstriction and structural remodeling of cerebral arteries. Based on these results, the purpose of this study was to test the hypothesis that 13 d of spaceflight [Space Transportation System (STS)‐135 shuttle mission] enhances myogenic vasoconstriction, increases medial wall thickness, and elicits no change in the mechanical properties of mouse cerebral arteries. Basilar and posterior communicating arteries (PCAs) were isolated from 9‐wk‐old female C57BL/6 mice for in vitro vascular and mechanical testing. Contrary to that hypothesized, myogenic vasoconstrictor responses were lower and vascular distensibility greater in arteries from spaceflight group (SF) mice (n=7) relative to ground‐based control group (GC) mice (n=12). Basilar artery maximal diameter was greater in SF mice (SF: 236±9 μm and GC: 215±5 μm) with no difference in medial wall thickness (SF: 12.4±1.6 μm; GC: 12.2±1.2 μm). Stiffness of the PCA, as characterized via nanoindentation, was lower in SF mice (SF: 3.4±0.3 N/m; GC: 5.4±0.8 N/m). Collectively, spaceflight‐induced reductions in myogenic vasoconstriction and stiffness and increases in maximal diameter of cerebral arteries signify that elevations in brain blood flow may occur during spaceflight. Such changes in cerebral vascular control of perfusion could contribute to increases in intracranial pressure and an associated impairment of visual acuity in astronauts during spaceflight.—Taylor, C. R., Hanna, M., Behnke, B. J., Stabley, J. N., McCullough, D. J., Davis III, R. T., Ghosh, P., Papadopoulos, A., Muller‐Delp, J. M., Delp, M. D. Spaceflight‐induced alterations in cerebral artery vasoconstrictor, mechanical, and structural properties: implications for elevated cerebral perfusion and intracranial pressure. FASEB J. 27, 2282–2292 (2013). www.fasebj.org

Effectiveness of cold water immersion in the treatment of exertional heat stroke at the Falmouth Road Race.

PURPOSE This study aimed to investigate the effectiveness (speed of cooling and survival rates) of cold water immersion (CWI) in the treatment of patients with exertional heat stroke (EHS). Secondly, this study aimed to compare cooling rates on the basis of gender, age, and initial rectal temperature (Tr). METHODS Eighteen years of finish line medical tent patient records were obtained from the exertional heat illness treatment area at the Falmouth Road Race. Study participants included patients with EHS who were treated with CWI in the medical tent. The number of EHS cases was recorded for each year, and incidence was established on the basis of the number of finishers. Overall cooling rate and differences between initial Tr, age, and sex were evaluated. RESULTS A total of 274 cases of EHS was observed over the 18 yr of collected data. A mean of 15.2 ± 13.0 EHS cases per year was recorded, with an overall incidence of 2.13 ± 1.62 EHS cases per 1000 finishers. The average initial Tr was 41.44°C ± 0.63°C, and the average cooling rate for patients with EHS was 0.22°C·min ± 0.11°C·min. CWI resulted in a 100% survival rate for all patients with EHS. No significant interactions between cooling rate and initial Tr (P = 0.778), sex (P = 0.89), or age (P = 0.70) were observed. CONCLUSIONS CWI was found to effectively treat all cases of EHS observed in this study. CWI provided similar treatment outcomes in all patients, with no significant differences noted on the basis of initial Tr, age, or sex. On the basis of the 100% survival rate from EHS in this large cohort, it is recommended that immediate (on site) CWI be implemented for the treatment of EHS.

Reproducibility of endurance capacity and VO2peak in male Sprague-Dawley rats.

The rat model of treadmill running is an invaluable tool for the investigation of experimentally and pathologically induced alterations in exercise performance. Interpretation of such data often presumes knowledge of the within-rat reproducibility of performance measures; however, the literature is bereft of this information. We tested the hypothesis that within-rat exercise endurance capacity and peak O(2) uptake (Vo(2peak)) are highly reproducible across five measurements spanning approximately 5 wk when assessed with treadmill performance protocols. Male Sprague-Dawley rats (n = 13) performed five graded exercise tolerance tests to fatigue and five maximal exercise tests on a motor-driven treadmill for determination of endurance capacity and Vo(2peak), respectively. There were no differences (P = 0.47) in average time to fatigue among any of the five exercise tolerance tests (average range 45.9-52.1 min), and the average within-rat coefficient of variation (CV) over the five runs was 0.13. There were no differences (P > 0.05) among the average CVs from any consecutive weekly exercise tolerance tests (range of 4 CVs 0.06-0.10). As expected with the increase in body mass, relative Vo(2peak) decreased (average range from 80.1 to 75.7 ml x min(-1) x kg(-1), P < 0.05) throughout the five maximal exercise tests. However, there were no differences (P = 0.63) in the average within-rat CVs among any consecutive Vo(2peak) tests (range of 4 CVs 0.03-0.04), and the average within-rat CV for all five tests was 0.06. The present data obtained from the protocols described herein demonstrate that within-rat measurements of endurance capacity and Vo(2peak) are highly reproducible. These results have significant implications for improving and refining exercise testing and experimental designs.

Effects of spaceflight and ground recovery on mesenteric artery and vein constrictor properties in mice

Following exposure to microgravity, there is a reduced ability of astronauts to augment peripheral vascular resistance, often resulting in orthostatic hypotension. The purpose of this study was to test the hypothesis that mesenteric arteries and veins will exhibit diminished vasoconstrictor responses after spaceflight. Mesenteric arteries and veins from female mice flown on the Space Transportation System (STS)‐131 (n=11), STS‐133 (n=6), and STS‐135 (n=3) shuttle missions and respective ground‐based control mice (n=30) were isolated for in vitro experimentation. Vasoconstrictor responses were evoked in arteries via norepinephrine (NE), potassium chloride (KCl), and caffeine, and in veins through NE across a range of intraluminal pressures (2–12 cmH2O). Vasoconstriction to NE was also determined in mesenteric arteries at 1, 5, and 7 d postlanding. In arteries, maximal constriction to NE, KCl, and caffeine were reduced immediately following spaceflight and 1 d postflight. Spaceflight also reduced arterial ryanodine receptor‐3 mRNA levels. In mesenteric veins, there was diminished constriction to NE after flight. The results indicate that the impaired vasoconstriction following spaceflight occurs through the ryanodine receptor‐mediated intracellular Ca2+ release mechanism. Such vascular changes in astronauts could compromise the maintenance of arterial pressure during orthostatic stress.—Behnke, B. J., Stabley, J. N., McCullough, D. J., Davis, R. T., III, Dominguez, J. M., II, Muller‐Delp, J. M., Delp, M. D. Effects of spaceflight and ground recovery on mesenteric artery and vein constrictor properties in mice. FASEB J. 27, 399–409 (2013). www.fasebj.org

Effects of aging and exercise training on spinotrapezius muscle microvascular Po2 dynamics and vasomotor control

With advancing age, there is a reduction in exercise tolerance, resulting, in part, from a perturbed ability to match O(2) delivery to uptake within skeletal muscle. In the spinotrapezius muscle (which is not recruited during incline treadmill running) of aged rats, we tested the hypotheses that exercise training will 1) improve the matching of O(2) delivery to O(2) uptake, evidenced through improved microvascular Po(2) (Pm(O(2))), at rest and throughout the contractions transient; and 2) enhance endothelium-dependent vasodilation in first-order arterioles. Young (Y, ∼6 mo) and aged (O, >24 mo) Fischer 344 rats were assigned to control sedentary (YSED; n = 16, and OSED; n = 15) or exercise-trained (YET; n = 14, and OET; n = 13) groups. Spinotrapezius blood flow (via radiolabeled microspheres) was measured at rest and during exercise. Phosphorescence quenching was used to quantify Pm(O(2)) in vivo at rest and across the rest-to-twitch contraction (1 Hz, 5 min) transition in the spinotrapezius muscle. In a follow-up study, vasomotor responses to endothelium-dependent (acetylcholine) and -independent (sodium nitroprusside) stimuli were investigated in vitro. Blood flow to the spinotrapezius did not increase above resting values during exercise in either young or aged groups. Exercise training increased the precontraction baseline Pm(O(2)) (OET 37.5 ± 3.9 vs. OSED 24.7 ± 3.6 Torr, P < 0.05); the end-contracting Pm(O(2)) and the time-delay before Pm(O(2)) fell in the aged group but did not affect these values in the young. Exercise training improved maximal vasodilation in aged rats to acetylcholine (OET 62 ± 16 vs. OSED 27 ± 16%) and to sodium nitroprusside in both young and aged rats. Endurance training of aged rats enhances the Pm(O(2)) in a nonrecruited skeletal muscle and is associated with improved vascular smooth muscle function. These data support the notion that improvements in vascular function with exercise training are not isolated to the recruited muscle.

Differential effects of aging and exercise on intra-abdominal adipose arteriolar function and blood flow regulation

Adipose tissue (AT), which typically comprises an increased percentage of body mass with advancing age, receives a large proportion of resting cardiac output. During exercise, an old age-associated inability to increase vascular resistance within the intra-abdominal AT may compromise the ability of the cardiovascular system to redistribute blood flow to the active musculature, contributing to the decline in exercise capacity observed in this population. We tested the hypotheses that 1) there would be an elevated perfusion of AT during exercise with old age that was associated with diminished vasoconstrictor responses of adipose-resistance arteries, and 2) chronic exercise training would mitigate the age-associated alterations in AT blood flow and vascular function. Young (6 mo; n = 40) and old (24 mo; n = 28) male Fischer 344 rats were divided into young sedentary (YSed), old sedentary (OSed), young exercise trained (YET), or old exercise trained (OET) groups, where training consisted of 10-12 wk of treadmill exercise. In vivo blood flow at rest and during exercise and in vitro α-adrenergic and myogenic vasoconstrictor responses in resistance arteries from AT were measured in all groups. In response to exercise, there was a directionally opposite change in AT blood flow in the OSed group (≈ 150% increase) and YSed (≈ 55% decrease) vs. resting values. Both α-adrenergic and myogenic vasoconstriction were diminished in OSed vs. YSed AT-resistance arteries. Exercise training resulted in a similar AT hyperemic response between age groups during exercise (YET, 9.9 ± 0.5 ml · min(-1) · 100(-1) g; OET, 8.1 ± 0.9 ml · min(-1) · 100(-1) g) and was associated with enhanced myogenic and α-adrenergic vasoconstriction of AT-resistance arteries from the OET group relative to OSed. These results indicate that there is an inability to increase vascular resistance in AT during exercise with old age, due, in part, to a diminished vasoconstriction of AT arteries. Furthermore, the results indicate that exercise training can augment vasoconstriction of AT arteries and mitigate age-related alterations in the regulation of AT blood flow during exercise.

Aging and exercise training reduce testes microvascular Po2 and alter vasoconstrictor responsiveness in testicular arterioles

Testicular function and associated testosterone concentration decline with advancing age, and an impaired O₂ supply may contribute, in part, to this reduction. We hypothesized that there would be a reduced microvascular Po₂ (Po₂(m)) in the testes from aged rats, and this reduced Po₂(m) would be associated with impaired vasomotor control in isolated resistance arterioles. In addition, given the positive effect of exercise on microvascular Po₂ and arteriolar function, we further hypothesized that there would be an enhanced Po₂(m) in the testes from aged animals after aerobic exercise training. Testicular Po₂(m) was measured in vivo via phosphorescence quenching in young and aged sedentary (SED) and exercise-trained (ET; 15 m/min treadmill walking, 15-degree incline, 5 days/wk for 10 wk) male Fischer-344 rats. Vasoconstriction to α-adrenergic [norepinephrine (NE) and phenylephrine (PE)] and myogenic stimuli in testicular arterioles was assessed in vitro. In the SED animals, testicular Po₂(m) was reduced by ∼50% with old age (aged SED 11.8 ± 1.9 vs. young SED 22.1 ± 1.1 mmHg; P = 0.0001). Contrary to our hypothesis, exercise training did not alter Po₂(m) in the aged group and reduced testicular Po₂(m) in the young animals, abolishing age-related differences (young ET, 10.0 ± 0.8 vs. aged ET, 10.7 ± 0.9 mmHg; P = 0.37). Vasoconstrictor responsiveness to NE and PE was diminished in aged compared with young (NE: young SED, 58 ± 2 vs. aged SED, 47 ± 2%; P = 0.001) (PE: young SED, 51 ± 3 vs. aged SED, 36 ± 5%; P = 0.008). Exercise training did not alter maximal vasoconstriction to NE in young or aged groups. In summary, advancing age is associated with a reduced testis Po₂(m) and impaired adrenergic vasoconstriction. The diminished testicular microvascular driving pressure of O₂ and associated vascular dysfunction provides mechanistic insight into the old age-related decrease in testicular function, and a reduced Po₂(m) may contribute, in part, to reduced fertility markers after exercise training.