Diversity and Molecular Evolution of Nonvisual Opsin Genes across Environmental, Developmental, and Morphological Adaptations in Frogs.

Nonvisual opsins are transmembrane proteins expressed in the eyes and other tissues of many animals. When paired with a light-sensitive chromophore, nonvisual opsins form photopigments involved in various nonvisual, light-detection functions including circadian rhythm regulation, light-seeking behaviors, and seasonal responses. Here, we investigate the molecular evolution of nonvisual opsin genes in anuran amphibians (frogs and toads). We test several evolutionary hypotheses including the predicted loss of nonvisual opsins due to nocturnal ancestry and potential functional differences in nonvisual opsins resulting from environmental light variation across diverse anuran ecologies. Using whole-eye transcriptomes of 81 species, combined with genomes, multitissue transcriptomes, and independently annotated genes from an additional 21 species, we identify which nonvisual opsins are present in anuran genomes and those that are also expressed in the eyes, compare selective constraint among genes, and test for potential adaptive evolution by comparing selection between discrete ecological classes. At the genomic level, we recovered all 18 ancestral vertebrate nonvisual opsins, indicating that anurans demonstrate the lowest documented amount of opsin gene loss among ancestrally nocturnal tetrapods. We consistently found expression of 14 nonvisual opsins in anuran eyes and detected positive selection in a subset of these genes. We also found shifts in selective constraint acting on nonvisual opsins in frogs with differing activity periods, habitats, distributions, life histories, and pupil shapes, which may reflect functional adaptation. Although many nonvisual opsins remain poorly understood, these findings provide insight into the diversity and evolution of these genes across anurans, filling an important gap in our understanding of vertebrate opsins and setting the stage for future research on their functional evolution across taxa.

Diversity and Evolution of Frog Visual Opsins: Spectral Tuning and Adaptation to Distinct Light Environments.

Visual systems adapt to different light environments through several avenues including optical changes to the eye and neurological changes in how light signals are processed and interpreted. Spectral sensitivity can evolve via changes to visual pigments housed in the retinal photoreceptors through gene duplication and loss, differential and coexpression, and sequence evolution. Frogs provide an excellent, yet understudied, system for visual evolution research due to their diversity of ecologies (including biphasic aquatic-terrestrial life cycles) that we hypothesize imposed different selective pressures leading to adaptive evolution of the visual system, notably the opsins that encode the protein component of the visual pigments responsible for the first step in visual perception. Here, we analyze the diversity and evolution of visual opsin genes from 93 new eye transcriptomes plus published data for a combined dataset spanning 122 frog species and 34 families. We find that most species express the four visual opsins previously identified in frogs but show evidence for gene loss in two lineages. Further, we present evidence of positive selection in three opsins and shifts in selective pressures associated with differences in habitat and life history, but not activity pattern. We identify substantial novel variation in the visual opsins and, using microspectrophotometry, find highly variable spectral sensitivities, expanding known ranges for all frog visual pigments. Mutations at spectral-tuning sites only partially account for this variation, suggesting that frogs have used tuning pathways that are unique among vertebrates. These results support the hypothesis of adaptive evolution in photoreceptor physiology across the frog tree of life in response to varying environmental and ecological factors and further our growing understanding of vertebrate visual evolution.

Fasting for 20 h does not affect exercise-induced increases in circulating BDNF in humans.

Intermittent fasting and exercise provide neuroprotection from age-related cognitive decline. A link between these two seemingly distinct stressors is their capability to steer the brain away from exclusively glucose metabolism. This cerebral substrate switch has been implicated in upregulating brain-derived neurotrophic factor (BDNF), a protein involved in neuroplasticity, learning and memory, and may underlie some of these neuroprotective effects. We examined the isolated and interactive effects of (1) 20-h fasting, (2) 90-min light exercise, and (3) high-intensity exercise on peripheral venous BDNF in 12 human volunteers. A follow-up study isolated the influence of cerebrovascular shear stress on circulating BDNF. Fasting for 20 h decreased glucose and increased ketones (P ≤ 0.0157) but had no effect on BDNF (P ≥ 0.4637). Light cycling at 25% of peak oxygen uptake ( V ̇ O 2 peak ${\dot V_{{{\rm{O}}_{\rm{2}}}{\rm{peak}}}}$ ) increased serum BDNF by 6 ± 8% (independent of being fed or fasted) and was mediated by a 7 ± 6% increase in platelets (P < 0.0001). Plasma BDNF was increased from 336 pg l-1 [46,626] to 390 pg l-1 [127,653] by 90-min of light cycling (P = 0.0128). Six 40-s intervals at 100% of V ̇ O 2 peak ${\dot V_{{{\rm{O}}_{\rm{2}}}{\rm{peak}}}}$ increased plasma and serum BDNF, as well as the BDNF-per-platelet ratio 4- to 5-fold more than light exercise did (P ≤ 0.0044). Plasma BDNF was correlated with circulating lactate during the high-intensity intervals (r = 0.47, P = 0.0057), but not during light exercise (P = 0.7407). Changes in cerebral shear stress - whether occurring naturally during exercise or induced experimentally with inspired CO2 - did not correspond with changes in BDNF (P ≥ 0.2730). BDNF responses to low-intensity exercise are mediated by increased circulating platelets, and increasing either exercise duration or particularly intensity is required to liberate free BDNF. KEY POINTS: Intermittent fasting and exercise both have potent neuroprotective effects and an acute upregulation of brain-derived neurotrophic factor (BDNF) appears to be a common mechanistic link. Switching the brain's fuel source from glucose to either ketone bodies or lactate, i.e. a cerebral substrate switch, has been shown to promote BDNF production in the rodent brain. Fasting for 20 h caused a 9-fold increase in ketone body delivery to the brain but had no effect on any metric of BDNF in peripheral circulation at rest. Prolonged (90 min) light cycling exercise increased plasma- and serum-derived BDNF irrespective of being fed or fasted and seemed to be independent of changes in cerebral shear stress. Six minutes of high-intensity cycling intervals increased every metric of circulating BDNF by 4 to 5 times more than prolonged low-intensity cycling; the increase in plasma-derived BDNF was correlated with a 6-fold increase in circulating lactate irrespective of feeding or fasting. Compared to 1 day of fasting with or without prolonged light exercise, high-intensity exercise is a much more efficient means to increase BDNF in circulation.

The athlete's vein: venous adaptations in the lower limbs of endurance athletes.

Endurance exercise induces cardiovascular adaptations; the athletic phenotypes of the heart and arteries are well characterized, but few studies have investigated the effects of chronic exercise on the venous system. The aim of this study was to describe the anatomy and function of lower-limb deep and superficial veins in athletes compared with controls. Endurance-trained athletes and untrained controls (13 males, 7 females per group) were examined using ultrasound to measure vein diameter and flow, and air plethysmography to assess calf venous volume dynamics and muscle pump function at rest, during a single step, ambulation (10 steps) and after acute treadmill exercise (30 min ∼80% age-predicted heart rate maximum). Diameters of three of the seven deep veins assessed were larger in athletes (P ≤ 0.0167) and more medial calf perforators were detectable (5 vs. 3, P = 0.0039). Calf venous volume was 22% larger in athletes (P = 0.0057), and calf muscle pump ejection volume and ambulatory venous volume after 10 steps were both greater in athletes (20 and 46% respectively, P ≤ 0.0482). Following acute exercise, flow recovery profiles in deep and superficial veins draining the leg were not different between groups, despite athletes performing approximately four times more work. After exercise, venous volume and ejection volume were reduced by ∼20% in athletes with no change in controls (interaction, P ≤ 0.0372) and although ambulatory venous volume reduced, this remained greater in athletes. These findings highlight venous adaptations that compensate for the demands of regular endurance exercise, all of which are suited to enhance flow through the lower-limb venous system.NEW & NOTEWORTHY Although much literature exists describing adaptations to the heart and arteries in response to endurance exercise training, less is known about the effects on the venous system. Characteristics of "the athlete's vein" described here include deep and perforator vein remodeling, improved drainage, and greater calf venous volume at rest and on calf muscle pump activation. Following exercise, athletes demonstrated prompt flow recovery and appropriate volume reductions, and veins beneficially adapt to better tolerate the demands of regular physical activity.

Physiological relationship between cardiorespiratory fitness and fitness for surgery: a narrative review.

Epidemiological evidence has highlighted a strong relationship between cardiorespiratory fitness and surgical outcomes; specifically, fitter patients possess heightened resilience to withstand the surgical stress response. This narrative review draws on exercise and surgical physiology research to discuss and hypothesise the potential mechanisms by which higher fitness affords perioperative benefit. A higher fitness, as indicated by higher peak rate of oxygen consumption and ability to sustain metabolic homeostasis (i.e. higher anaerobic threshold) is beneficial postoperatively when metabolic demands are increased. However, the associated adaptations with higher fitness, and the related participation in regular exercise or physical activity, might also underpin the observed perioperative benefit through a process of hormesis, a protective adaptive response to the moderate and intermittent stress of exercise. Potential mediators discussed include greater antioxidant capacity, metabolic flexibility, glycaemic control, lean body mass, and improved mood.

Transcriptomic evidence for visual adaptation during the aquatic to terrestrial metamorphosis in leopard frogs.

BACKGROUND: Differences in morphology, ecology, and behavior through ontogeny can result in opposing selective pressures at different life stages. Most animals, however, transition through two or more distinct phenotypic phases, which is hypothesized to allow each life stage to adapt more freely to its ecological niche. How this applies to sensory systems, and in particular how sensory systems adapt across life stages at the molecular level, is not well understood. Here, we used whole-eye transcriptomes to investigate differences in gene expression between tadpole and juvenile southern leopard frogs (Lithobates sphenocephalus), which rely on vision in aquatic and terrestrial light environments, respectively. Because visual physiology changes with light levels, we also tested the effect of light and dark exposure. RESULTS: We found 42% of genes were differentially expressed in the eyes of tadpoles versus juveniles and 5% for light/dark exposure. Analyses targeting a curated subset of visual genes revealed significant differential expression of genes that control aspects of visual function and development, including spectral sensitivity and lens composition. Finally, microspectrophotometry of photoreceptors confirmed shifts in spectral sensitivity predicted by the expression results, consistent with adaptation to distinct light environments. CONCLUSIONS: Overall, we identified extensive expression-level differences in the eyes of tadpoles and juveniles related to observed morphological and physiological changes through metamorphosis and corresponding adaptive shifts to improve vision in the distinct aquatic and terrestrial light environments these frogs inhabit during their life cycle. More broadly, these results suggest that decoupling of gene expression can mediate the opposing selection pressures experienced by organisms with complex life cycles that inhabit different environmental conditions throughout ontogeny.

Contribution of the carotid body to thermally mediated hyperventilation in humans.

Humans hyperventilate under heat and cold strain. This hyperventilatory response has detrimental consequences including acid-base dysregulation, dyspnoea, decreased cerebral blood flow and accelerated brain heating. The ventilatory response to hypoxia is exaggerated under whole-body heating and cooling, indicating that altered carotid body function might contribute to thermally mediated hyperventilation. To address whether the carotid body might contribute to heat- and cold-induced hyperventilation, we indirectly measured carotid body tonic activity via hyperoxia, and carotid body sensitivity via hypoxia, under graded heat and cold strain in 13 healthy participants in a repeated-measures design. We hypothesised that carotid body tonic activity and sensitivity would be elevated in a dose-dependent manner under graded heat and cold strain, thereby supporting its role in driving thermally mediated hyperventilation. Carotid body tonic activity was increased in a dose-dependent manner with heating, reaching 175% above baseline (P < 0.0005), and carotid body suppression with hyperoxia removed all of the heat-induced increase in ventilation (P = 0.9297). Core cooling increased carotid body activity by up to 250% (P < 0.0001), but maximal values were reached with mild cooling and thereafter plateaued. Carotid body sensitivity to hypoxia was profoundly increased by up to 180% with heat stress (P = 0.0097), whereas cooling had no detectable effect on hypoxic sensitivity. In summary, cold stress increased carotid body tonic activity and this effect was saturated with mild cooling, whereas heating had clear dose-dependent effects on carotid body tonic activity and sensitivity. These dose-dependent effects with heat strain indicate that the carotid body probably plays a primary role in driving heat-induced hyperventilation. KEY POINTS: Humans over-breathe (hyperventilate) when under heat and cold stress, and though this has detrimental physiological repercussions, the mechanisms underlying this response are unknown. The carotid body, a small organ that is responsible for driving hyperventilation in hypoxia, was assessed under incremental heat and cold strain. The carotid body drive to breathe, as indirectly assessed by transient hyperoxia, increased in a dose-dependent manner with heating, reaching 175% above baseline; cold stress similarly increased the carotid body drive to breathe, but did not show dose-dependency. Carotid body sensitivity, as indirectly assessed by hypoxic ventilatory responses, was profoundly increased by 70-180% with mild and severe heat strain, whereas cooling had no detectable effect. Carotid body hyperactivity and hypersensitivity are two interrelated mechanisms that probably underlie the increased drive to breathe with heat strain, whereas carotid body hyperactivity during mild cooling may play a subsidiary role in cold-induced hyperventilation.

Ocular lens morphology is influenced by ecology and metamorphosis in frogs and toads.

The shape and relative size of an ocular lens affect the focal length of the eye, with consequences for visual acuity and sensitivity. Lenses are typically spherical in aquatic animals with camera-type eyes and axially flattened in terrestrial species to facilitate vision in optical media with different refractive indices. Frogs and toads (Amphibia: Anura) are ecologically diverse, with many species shifting from aquatic to terrestrial ecologies during metamorphosis. We quantified lens shape and relative size using 179 micro X-ray computed tomography scans of 126 biphasic anuran species and tested for correlations with life stage, environmental transitions, adult habits and adult activity patterns. Across broad phylogenetic diversity, tadpole lenses are more spherical than those of adults. Biphasic species with aquatic larvae and terrestrial adults typically undergo ontogenetic changes in lens shape, whereas species that remain aquatic as adults tend to retain more spherical lenses after metamorphosis. Further, adult lens shape is influenced by adult habit; notably, fossorial adults tend to retain spherical lenses following metamorphosis. Finally, lens size relative to eye size is smaller in aquatic and semiaquatic species than other adult ecologies. Our study demonstrates how ecology shapes visual systems, and the power of non-invasive imaging of museum specimens for studying sensory evolution.

Pulsatile flow in venous perforators of the lower limb.

Teaching traditionally asserts that the arterial pressure pulse is dampened across the capillary bed to the extent that pulsatility is nonexistent in the venous circulation of the lower limbs. Herein, we present evidence of transmission of arterial pulsations across the capillary network into perforator veins in the lower limbs of healthy, heat-stressed humans. Perforator veins are connections from the superficial veins that drain into the deep veins. When assessed using ultrasound at rest, they infrequently demonstrate flow, and a pulsatile flow waveform is not described. We investigated perforator vein pulsatility in 10 young, healthy volunteers who underwent passive heating by +2°C core body temperature via a hot-water-perfused suit, and 5 who also underwent active heating by +2°C via low-intensity cycling while wearing the hot-water-perfused suit. At +0.5°C increments in temperature, blood velocity in an ankle perforator vein was measured using duplex ultrasound. In all perforators with heating, sustained flow was demonstrated, with a pulsatile waveform that was synchronous with the cardiac cycle. The maximum velocity was 30 ± 13 cm/s with passive heating and approximately half with active heating (P = 0.04). The small veins of the skin at the ankle also demonstrated increased perfusion with pulsatility, seen with low-velocity microvascular imaging technology. We consider explanations for this pulsatility and conclude that it is propagated from the arterial inflow through the skin microcirculation as a result of increased dilatation and flow volume and that this is a normal response to increased skin blood flow.

Acute physiological and psychophysical responses to different modes of heat stress.

NEW FINDINGS: What is the central question of this study? What are the profiles of acute physiological and psychophysical strain during and in recovery from different modes of heating, and to what extent do these diminish after repeated exposure? What is the main finding and its importance? Mode of heating affects the strain profiles during heat stress and recovery. Exercise in the heat incurred the greatest cardiovascular strain during heating and recovery. Humid heat was poorly tolerated despite heat strain being no greater than in other heating modes, and tolerance did not improve with multiple exposures. ABSTRACT: Heat stress is common and arises endogenously and exogenously. It can be acutely hazardous while also increasingly advocated to drive health and performance-related adaptations. Yet, the nature of strain (deviation in regulated variables) imposed by different heating modes is not well established, despite the potential for important differences. We, therefore, compared three modes of heat stress for thermal, cardiovascular and perceptual strain profiles during exposure and recovery when experienced as a novel stimulus and an accustomed stimulus. In a crossover design, 13 physically active participants (five females) underwent 5 days of 60-min exposures to hot water immersion (40°C), sauna (55°C, 54% relative humidity) and exercise in the heat (40°C, 52% relative humidity), and a thermoneutral water immersion control (36.5°C), each separated by ≥4 weeks. Physiological (thermal, cardiovascular, haemodynamic) and psychophysical strain responses were assessed on days 1 and 5. Sauna evoked the warmest skin (40°C; P < 0.001) but exercise in the heat caused the largest increase in core temperature, sweat rate, heart rate (post hoc comparisons all P < 0.001) and systolic blood pressure (P ≤ 0.002), and possibly decrease in diastolic blood pressures (P ≤ 0.130), regardless of day. Thermal sensation and feeling state were more favourable on day 5 than on day 1 (P ≤ 0.021), with all modes of heat being equivalently uncomfortable (P ≥ 0.215). Plasma volume expanded the largest extent during immersions (P < 0.001). The current data highlight that exercising in the heat generates a more complex strain profile, while passive heat stress in humid heat has lower tolerance and more cardiovascular strain than hot water immersion.

A crossover control study of three methods of heat acclimation on the magnitude and kinetics of adaptation.

NEW FINDINGS: What is the central question to the study? Are primary indices of heat adaptation (e.g., expansion of plasma volume and reduction in resting core temperature) differentially affected by the three major modes of short-term heat acclimation, that is, exercise in the heat, hot water immersion and sauna? What it the main finding and its importance? The three modes elicited typical adaptations expected with short-term heat acclimation, but these were not significantly different between modes. This comparison has not previously been made and highlights that individuals can expect similar adaptation to heat regardless of the mode used. ABSTRACT: Heat acclimation (HA) can improve heat tolerance and cardiovascular health. The mode of HA potentially impacts the magnitude and time course of adaptations, but almost no comparative data exist. We therefore investigated adaptive responses to three common modes of HA, particularly with respect to plasma volume. Within a crossover repeated-measures design, 13 physically active participants (five female) undertook four, 5-day HA regimes (60 min/day) in randomised order, separated by ≥4 weeks. Rectal temperature (Tre ) was clamped at neutrality via 36.6°C (thermoneutral) water immersion (TWI; i.e., control condition), or raised by 1.5°C via heat stress in 40°C water, sauna (55°C, 52% relative humidity), or exercise in humid heat (40°C, 52% relative humidity; ExH). Adaptation magnitude was assessed as the pooled response across days 4-6, while kinetics was assessed via the 6-day time series. Plasma volume expansion was similar in all heated conditions but only higher than TWI in exercise in the heat (ExH) (by 4%, P = 0.036). Approximately two-thirds of the expansion was attained within the initial 24 h and was moderately related to that present on day 6, regardless of HA mode (r = 0.560-0.887). Expansion was mediated by conservation of both sodium and albumin content, with little evidence for these having differential roles between modes (P = 0.706 and 0.320, respectively). Resting Tre decreased by 0.1-0.3°C in all heated conditions, and systolic blood pressure decreased by 4 mmHg, but not differentially between conditions (P ≥ 0.137). In conclusion, HA mode did not substantially affect the magnitude or rate of adaptation in key resting markers of short-term HA.

Influence of the mode of heating on cerebral blood flow, non-invasive intracranial pressure and thermal tolerance in humans.

KEY POINTS: The human brain is particularly vulnerable to heat stress; this manifests as impaired cognition, orthostatic tolerance, work capacity and eventually, brain death. The brain's limitation in the heat is often ascribed to inadequate cerebral blood flow (CBF), but elevated intracranial pressure is commonly observed in mammalian models of heat stroke and can on its own cause functional impairment. The CBF response to incremental heat strain was dependent on the mode of heating, decreasing by 30% when exposed passively to hot, humid air (sauna), while remaining unchanged or increasing with passive hot-water immersion (spa) and exercising in a hot environment. Non-invasive intracranial pressure estimates (nICP) were increased universally by 18% at volitional thermal tolerance across all modes of heat stress, and therefore may play a contributing role in eliciting thermal tolerance. The sauna, more so than the spa or exercise, poses a greater challenge to the brain under mild to severe heating due to lower blood flow but similarly increased nICP. ABSTRACT: The human brain is particularly vulnerable to heat stress; this manifests as impaired cognitive function, orthostatic tolerance, work capacity, and eventually, brain death. This vulnerability is often ascribed to inadequate cerebral blood flow (CBF); however, elevated intracranial pressure (ICP) is also observed in mammalian models of heat stroke. We investigated the changes in CBF with incremental heat strain under three fundamentally different modes of heating, and assessed whether heating per se increased ICP. Fourteen fit participants (seven female) were heated to thermal tolerance or 40°C core temperature (Tc ; oesophageal) via passive hot-water immersion (spa), passive hot, humid air exposure (sauna), cycling exercise, and cycling exercise with CO2 inhalation to prevent heat-induced hypocapnia. CBF was measured with duplex ultrasound at each 0.5°C increment in Tc and ICP was estimated non-invasively (nICP) from optic nerve sheath diameter at thermal tolerance. At thermal tolerance, CBF was decreased by 30% in the sauna (P < 0.001), but was unchanged in the spa or with exercise (P ≥ 0.140). CBF increased by 17% when end-tidal PCO2 was clamped at eupnoeic pressure (P < 0.001). On the contrary, nICP increased universally by 18% with all modes of heating (P < 0.001). The maximum Tc was achieved with passive heating, and preventing hypocapnia during exercise did not improve exercise or thermal tolerance (P ≥ 0.146). Therefore, the regulation of CBF is dramatically different depending on the mode and dose of heating, whereas nICP responses are not. The sauna, more so than the spa or exercise, poses a greater challenge to the brain under equivalent heat strain.

Eye size and investment in frogs and toads correlate with adult habitat, activity pattern and breeding ecology.

Frogs and toads (Amphibia: Anura) display diverse ecologies and behaviours, which are often correlated with visual capacity in other vertebrates. Additionally, anurans exhibit a broad range of relative eye sizes, which have not previously been linked to ecological factors in this group. We measured relative investment in eye size and corneal size for 220 species of anurans representing all 55 currently recognized families and tested whether they were correlated with six natural history traits hypothesized to be associated with the evolution of eye size. Anuran eye size was significantly correlated with habitat, with notable decreases in eye investment among fossorial, subfossorial and aquatic species. Relative eye size was also associated with mating habitat and activity pattern. Compared to other vertebrates, anurans have relatively large eyes for their body size, indicating that vision is probably of high importance. Our study reveals the role that ecology and behaviour may have played in the evolution of anuran visual systems and highlights the usefulness of museum specimens, and importance of broad taxonomic sampling, for interpreting macroecological patterns.

The acute effect of resistance exercise on limb blood flow.

NEW FINDINGS: What is the central question of this study? How does resistance exercise affect peripheral haemodynamics in the active and inactive limb? What is the main finding and its importance? Preliminary data indicate that resistance exercise increases flow and shear rate in the active limb transiently. The same exercise has minimal, short-lasting influence on peripheral haemodynamics in the inactive limb, but further research is required to elaborate on resistance exercise-mediated changes in vascular function in active and inactive limbs. ABSTRACT: Current evidence indicates that to achieve maximum health benefits, regular resistance exercise should be a key component of structured physical activity. Several studies have revealed that regular resistance exercise may be associated with impaired vascular function, although this finding is inconsistent. Proposed explanations for impairment include substantial increases in blood pressure and increased retrograde blood flow in active limbs promoted by resistance exercise. However, few studies have examined the acute haemodynamics of resistance exercise in active - and even fewer in inactive - limbs. The purpose of this study was to characterise the haemodynamic responses in peripheral arteries in active and inactive limbs in response to resistance exercise using upper and lower limbs. Ten participants (five male, five female) familiar with resistance training performed three sets of 10 isotonic repetitions of right-sided bicep curls or knee extensions on separate days. Blood flow, shear rate and muscle oxygenation in the active and inactive limb, and blood pressure were measured before and for 3 min after each set. Blood flow increased in response to resistance exercise in the active limb (∼8-fold and ∼6-fold for the upper and lower limb respectively), with concurrent significant increases in mean and antegrade shear rate. In the inactive limb, blood flow more than doubled for both upper and lower limb exercise, transiently, with no significant change in retrograde shear rate. These acute blood flow profiles following resistance exercise are not indicative of long-term vessel impairment based on current understanding of blood flow and shear stress patterns.

Cerebrovascular haemodynamics during isometric resistance exercise with and without the Valsalva manoeuvre.

PURPOSE: To examine the interactive effects of VM and isometric resistance exercise on cerebral haemodynamics. METHODS: Eleven healthy participants (mean ± SD 28 ± 9 years; 2 females) completed 20-s bilateral isometric leg extension at 50% of maximal voluntary contraction with continued ventilation (RE), a 20-s VM at mouth pressure of 40 mmHg (VM), and a combination (RE + VM), in randomised order. Mean beat-to-beat blood velocity in the posterior (PCAvmean) and middle cerebral arteries (MCAvmean), vertebral artery blood flow, end-tidal partial pressure of CO2 and mean arterial pressure (MAP) were measured. RE data were time aligned to RE + VM and analysed according to standard VM phases. RESULTS: Interaction effects (VM phase × condition) were observed for MCAvmean, PCAvmean, vertebral artery blood flow and MAP (all ≤ 0.010). Phase I MCAvmean was greatest for RE [88 ± 19, vs. 71 ± 11 and 78 ± 12 cm s-1 for VM (P = 0.008) and RE + VM (P = 0.021), respectively]. Greater increases in MCAvmean than PCAvmean occurred in phase I of RE only (24 ± 15% vs. 16 ± 16%, post hoc P = 0.044). In phase IIb, MAP was lower in RE than RE + VM (115 ± 15 vs. 138 ± 21 mmHg, P = 0.004), but did not reduce MCAvmean (78 ± 8 vs. 79 ± 9 cm s-1, P = 0.579) or PCAvmean (45 ± 11 vs .46 ± 11 cm s-1, P = 0.617). Phase IIb MCAvmean and PCAvmean was lowest in VM (66 ± 6 and 39 ± 8 cm s-1, respectively, all P < 0.001), whereas in Phase IV, MCAvmean, PCAvmean and MAP were greater in VM than in RE and RE + VM (all P < 0.020). CONCLUSION: RE and RE + VM produce similar cerebrovascular responses despite different MAP profiles. However, the VM produced the greatest cerebrovascular challenge afterward.

Heat therapy vs. supervised exercise therapy for peripheral arterial disease: a 12-wk randomized, controlled trial.

Peripheral arterial disease (PAD) is characterized by lower limb atherosclerosis impairing blood supply and causing walking-induced leg pain or claudication. Adherence to traditional exercise training programs is poor due to these symptoms despite exercise being a mainstay of conservative treatment. Heat therapy improves many cardiovascular health outcomes, so this study tested if this was a viable alternative cardiovascular therapy for PAD patients. Volunteers with PAD were randomized to 12 wk of heat (n = 11; mean age 76 ± 8 yr, BMI 28.7 ± 3.5 kg/m2, 4 females) or exercise (n = 11; 74 ± 10 yr, 28.5 ± 6.8 kg/m2, 3 females). Heat involved spa bathing at ∼39°C, 3-5 days/wk for ≤30 min, followed by ≤30 min of callisthenics. Exercise involved ≤90 min of supervised walking and gym-based exercise, 1-2 days/wk. Following the interventions, total walking distance during a 6-min walk test increased (from ∼350 m) by 41 m (95% CI: [13, 69], P = 0.006) regardless of group, and pain-free walking distance increased (from ∼170 m) by 43 m ([22, 63], P < 0.001). Systolic blood pressure was reduced more following heat (-7 mmHg, [-4, -10], P < 0.001) than following exercise (-3 mmHg, [0, -6], P = 0.078), and diastolic and mean arterial pressure decreased by 4 mmHg in both groups (P = 0.002). There were no significant changes in blood volume, ankle-brachial index, or measures of vascular health. There were no differences in the improvement in functional or blood pressure outcomes between heat and exercise in individuals with PAD. NEW & NOTEWORTHY Heat therapy via hot-water immersion and supervised exercise both improved walking distance and resting blood pressure in peripheral arterial disease (PAD) patients over 12 wk. Adherence to heat therapy was excellent, and the heat intervention was well tolerated. The results of the current study indicate that heat therapy can improve functional ability and has potential as an effective cardiovascular conditioning tool for individuals with PAD.

Effects of Ischemic Preconditioning on Abdominal Aortic Aneurysm Repair: A Systematic Review and Meta-analysis.

BACKGROUND: Ischemic preconditioning is an innate mechanism of cytoprotection against ischemia, with potential for end-organ protection. The primary goal of this study was to systematically review the literature to determine the effect of ischemic preconditioning on outcomes after open and endovascular abdominal aortic aneurysm (AAA) repair. METHODS: The methodology followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. We included randomized clinical trials that evaluated the effect of remote ischemic preconditioning (RIPC) in reducing morbidity and mortality in patients undergoing open or endovascular AAA repair surgery. The primary outcomes were death, myocardial infarction, and renal impairment. Outcomes were addressed separately for open AAA repair and endovascular AAA repair (EVAR). Data were collected on patient characteristics, methodology, and preconditioning protocol for each trial. RESULTS: Nine trials of ischemic preconditioning in aortic aneurysm surgery were included with a total of 599 patients; 336 patients were included in the open AAA repair meta-analysis, and 263 patients were included in the EVAR meta-analysis. For both open and endovascular repairs, ischemic preconditioning did not have a significant effect on death, myocardial infarction, or renal impairment requiring dialysis. CONCLUSIONS: The randomized clinical trials investigating the effect of ischemic preconditioning on outcomes after open and endovascular AAA repair that have been completed to date have not been adequately powered to evaluate improvements in patient-important outcomes. The evidence is insufficient to support the use of ischemic preconditioning for AAA repair in clinical practice. The variability in treatment effect across studies may be explained by clinical and methodological heterogeneity.

Lower-limb hot-water immersion acutely induces beneficial hemodynamic and cardiovascular responses in peripheral arterial disease and healthy, elderly controls.

Passive heat induces beneficial perfusion profiles, provides substantive cardiovascular strain, and reduces blood pressure, thereby holding potential for healthy and cardiovascular disease populations. The aim of this study was to assess acute responses to passive heat via lower-limb, hot-water immersion in patients with peripheral arterial disease (PAD) and healthy, elderly controls. Eleven patients with PAD (age 71 ± 6 yr, 7 male, 4 female) and 10 controls (age 72 ± 7 yr, 8 male, 2 female) underwent hot-water immersion (30-min waist-level immersion in 42.1 ± 0.6°C water). Before, during, and following immersion, brachial and popliteal artery diameter, blood flow, and shear stress were assessed using duplex ultrasound. Lower-limb perfusion was measured also using venous occlusion plethysmography and near-infrared spectroscopy. During immersion, shear rate increased (P < 0.0001) comparably between groups in the popliteal artery (controls: +183 ± 26%; PAD: +258 ± 54%) and brachial artery (controls: +117 ± 24%; PAD: +107 ± 32%). Lower-limb blood flow increased significantly in both groups, as measured from duplex ultrasound (>200%), plethysmography (>100%), and spectroscopy, while central and peripheral pulse-wave velocity decreased in both groups. Mean arterial blood pressure was reduced by 22 ± 9 mmHg (main effect P < 0.0001, interaction P = 0.60) during immersion, and remained 7 ± 7 mmHg lower 3 h afterward. In PAD, popliteal shear profiles and claudication both compared favorably with those measured immediately following symptom-limited walking. A 30-min hot-water immersion is a practical means of delivering heat therapy to PAD patients and healthy, elderly individuals to induce appreciable systemic (chronotropic and blood pressure lowering) and hemodynamic (upper and lower-limb perfusion and shear rate increases) responses.