Subsequent Bout Research Articles

16-LB: N-Hydroxylethyl-1-Deoxynojirimycin (Miglitol) Infusion Rescues the Sympathoadrenal Response to Hypoglycemia following Antecedent Hypoglycemia in Rats

Antecedent hypoglycemia leads to a blunting of the sympathoadrenal response during subsequent hypoglycemia, which can largely be prevented by normalizing portal-mesenteric vein (PMV) glycemia during the antecedent bout. As SGLT3 has recently been implicated in PMV glucosensing, we hypothesized that PMV infusion of the imino sugar N-hydroxylethyl-1-deoxynojirimycin (miglitol), a potent SGLT3 agonist, during hypoglycemia would prevent or rescue the sympathoadrenal response to subsequent hypoglycemia. Wistar rats underwent hyperinsulinemic-hypoglycemic clamps on two consecutive days. Control animals were exposed to either euglycemia (EUG-CON: 5.73 ± 0.37 mM) or hypoglycemia (HYPO-CON: 2.39 ± 0.07 mM) on Day 1 without miglitol infusion, followed by a hypoglycemic bout on Day 2. Treatment groups were exposed to hypoglycemia (2.52 ± 0.07 mM) on both days with miglitol (1.45 μmol/kg/min) infused either upstream, perfusing the PMV glucosensors (PORups), or adjacent to the liver, bypassing the PMV glucosensors (PORadj), on Day 1 (PORups1, PORadj1) or Day2 (PORups2, PORadj2). Serial plasma samples drawn on the Day 2 experiment were assayed for glucose, insulin, epinephrine (EPI) and norepinephrine (NE). Compared to EUG-CON, peak EPI responses for HYPO-CON on Day 2 were significantly blunted (34.1 ± 4.3 vs. 15.4 ± 3.5 nmol/L; P < 0.05). EPI responses for PORups1 (11.8 ± 4.7 nmol/L) and PORadj1 (12.83 ± 3.4 nmol/L) were also suppressed on Day 2 compared with HYPO-CON (P<0.05). In contrast, EPI responses for PORups2 (31.5 ± 8.2 nmol/L) and PORadj2 (32.9 ± 13.2 nmol/L) were not significantly different from HYPO-CON (P = 0.74 and 0.90, respectively). NE demonstrated a similar trend to EPI. Conclusion: The impaired sympathoadrenal response following antecedent hypoglycemia in rats is restored by miglitol (NEOH-DNJ) treatment during a subsequent bout of hypoglycemia. Whether this is mediated via PMV glucosensors remains unclear. Disclosure A.J. Jokiaho: None. M. Winchester: None. C. Donovan: None. Funding JDRF

Intermittent reproduction, mortality patterns and lifetime breeding frequency of females in a population of the adder (Vipera berus).

Female adders (Vipera berus) are “capital breeders” that exhibit delayed maturity and intermittent reproductive frequency. We studied the attainment of sexual maturity, the initiation of annual breeding in mature females, the energy and mortality costs associated with breeding, the length of the reproductive cycle and female lifetime reproductive frequency. We use longitudinal data obtained during an 18-year (2000–2017) mark–recapture study in a large population of adders in northern Belgium. A minority (15%) of the females gave birth to their first litter when they attained the actual age of 3 years, upon surpassing a minimum snout-vent-length of 38 cm. However, most females reproduced for the first time when they were 4 years or older. In mature females, breeding in a given year depends to a large extent on their body condition at the onset of the active season, indicating that a threshold level of energy reserves is necessary to start a reproductive cycle. During breeding years females stop growing, lose about one-third of their initial body mass and are very emaciated after parturition. The decrease in relative body mass was most notable initially in the largest and fattiest females. During the non-breeding years, females forage intensely to rebuild their fat reserves; their abilities to do so will strongly affect whether and when they engage in subsequent reproductive bouts. We used a multistate mark–recapture analytical method to simultaneously estimate the capture and survival rates of breeding and non-breeding females, a necessary procedure to obtain accurate estimates of survival probabilities. The analysis indicated much higher capture rates during the breeding years, but did not reveal a substantial effect of reproductive state on annual survival rates. Although some females were observed to breed in successive years, the reproductive cycle was most often biennial or triennial. However, most females (ca. 70%) that attained sexual maturity reproduced only once during their lifetime, while a minority of the females (ca. 5%) were observed to breed on 3–5 annual occasions. On average, females produced only ca. 1.3 litters during their reproductive lifetime. The short reproductive lifetime is a consequence not only of mortality directly related to the reproductive activities, but also of mortality associated with recovering from the weakened post-parturient body condition during the long intervals (1–2 years) between reproductive bouts.

Repetitive hypoglycemia reduces activation of glucose-responsive neurons in C1 and C3 medullary brain regions to subsequent hypoglycemia.

The impaired ability of the autonomic nervous system to respond to hypoglycemia is termed “hypoglycemia-associated autonomic failure” (HAAF). This life-threatening phenomenon results from at least two recent episodes of hypoglycemia, but the pathology underpinning HAAF remains largely unknown. Although naloxone appears to improve hypoglycemia counterregulation under controlled conditions, hypoglycemia prevention remains the current mainstay therapy for HAAF. Epinephrine-synthesizing neurons in the rostroventrolateral (C1) and dorsomedial (C3) medulla project to the subset of sympathetic preganglionic neurons that regulate peripheral epinephrine release. Here we determined whether or not C1 and C3 neuronal activation is impaired in HAAF and whether or not 1 wk of hypoglycemia prevention or treatment with naloxone could restore C1 and C3 neuronal activation and improve HAAF. Twenty male Sprague-Dawley rats (250–300 g) were used. Plasma epinephrine levels were significantly increased after a single episode of hypoglycemia (n = 4; 5,438 ± 783 pg/ml vs. control 193 ± 27 pg/ml, P < 0.05). Repeated hypoglycemia significantly reduced the plasma epinephrine response to subsequent hypoglycemia (n = 4; 2,179 ± 220 pg/ml vs. 5,438 ± 783 pg/ml, P < 0.05). Activation of medullary C1 (n = 4; 50 ± 5% vs. control 3 ± 1%, P < 0.05) and C3 (n = 4; 45 ± 5% vs. control 4 ± 1%, P < 0.05) neurons was significantly increased after a single episode of hypoglycemia. Activation of C1 (n = 4; 12 ± 3%, P < 0.05) and C3 (n = 4; 19 ± 5%, P < 0.05) neurons was significantly reduced in the HAAF groups. Hypoglycemia prevention or treatment with naloxone did not restore the plasma epinephrine response or C1 and C3 neuronal activation. Thus repeated hypoglycemia reduced the activation of C1 and C3 neurons mediating adrenal medullary responses to subsequent bouts of hypoglycemia.

A neonicotinoid pesticide impairs foraging, but not learning, in free-flying bumblebees

Neonicotinoids are widely-used pesticides implicated in the decline of bees, known to have sub-lethal effects on bees’ foraging and colony performance. One proposed mechanism for these negative effects is impairment to bees’ ability to learn floral associations. However, the effects of neonicotinoids on learning performance have largely been addressed using a single protocol, where immobilized bees learn an association based on a single sensory modality. We thus have an incomplete understanding of how these pesticides affect bee learning in more naturalistic foraging scenarios. We carried out the first free-foraging study into the effects of acute exposure of a neonicotinoid (imidacloprid) on bumblebees’ (Bombus impatiens) ability to learn associations with visual stimuli. We uncovered dose-dependent detrimental effects on motivation to initiate foraging, amount of nectar collected, and initiation of subsequent foraging bouts. However, we did not find any impairment to bees’ ability to learn visual associations. While not precluding the possibility that other forms of learning are impaired, our findings suggest that some of the major effects of acute neonicotinoid exposure on foraging performance may be due to motivational and/or sensory impairments. In light of these findings, we discuss more broadly how pesticide effects on pollinator cognition might be studied.

Damage protective effects conferred by low-intensity eccentric contractions on arm, leg and trunk muscles.

Low-intensity eccentric contractions with a load corresponding to 10% of maximal voluntary isometric contraction strength (10% EC) attenuate muscle damage in a subsequent bout of higher-intensity eccentric contractions performed within 2 weeks for the elbow flexors, knee flexors and knee extensors. However, it is not known whether this strategy could be applied to other muscles. This study investigated whether 10% EC would confer damage protective effect on high-intensity eccentric contractions (80% EC) for nine different muscle groups. Untrained young men were placed to an experimental or a control group (n = 12/group). Experimental group performed 50 eccentric contractions with a load corresponding to 10% EC at 2 days prior to 50 eccentric contractions with 80% EC for the elbow flexors and extensors, pectoralis, knee flexors and extensors, plantar flexors, latissimus, abdominis and erector spinae. Control group performed 80% EC without 10% EC. Changes in maximal voluntary isometric contraction strength (MVC) and muscle soreness, plasma creatine kinase (CK) activity and myoglobin concentration after 80% EC were compared between groups by a mixed-factor ANOVA. MVC recovered faster (e.g., 6-31% greater MVC at 5 days post-exercise), and peak muscle soreness was 36-54% lower for Experimental than Control group for the nine muscles (P < 0.05). Increases in plasma CK activity and myoglobin concentration were smaller for Experimental (e.g., peak CK: 2763 ± 3459IU/L) than Control group (120,360 ± 50,158IU/L). These results showed that 10% EC was effective for attenuating the magnitude of muscle damage after 80% EC for all muscles, although the magnitude of the protective effect differed among the muscles.

Effect of postexercise temperature elevation on postexercise glycogen metabolism of isolated mouse soleus muscle.

The effects of temperature elevation after intense repeated contractions on glycogen and energy metabolism as well as contractile function of isolated mouse soleus muscle (slow twitch, oxidative) were investigated. Muscles were stimulated electrically to perform repeated tetanic contractions for 10 min at 25°C, which reduced tetanic force by ~85% and glycogen by 50%. After 120-min recovery at 25°C glycogen was fully restored (~125% of basal), whereas after recovery at 35°C glycogen decreased further (~25% of basal). Glycogen synthase fractional activity averaged 31.8 ± 3.1% (baseline = 33.8 ± 3.4%) after 120-min recovery at 25°C but was increased after recovery at 35°C (63.8 ± 4.8%; P < 0.001 vs. 25°C). Phosphorylase fractional and total activities were not affected by the higher temperature. However, recovery at 35°C resulted in a significantly higher content of the phosphorylase substrate inorganic phosphate (~20%; P < 0.01 vs. 25°C). Finally, fatigue development during a subsequent bout of repeated contractions at 25°C was similar after 120-min recovery at 25°C and 35°C. These data demonstrate that after intense contractions elevated temperature inhibits glycogen accumulation, likely by increasing the availability of the phosphorylase substrate inorganic phosphate, but has no effect on fatigue development. Thus after heat exposure phosphorylase plays a significant role in glycogen accumulation, and glycogen does not limit muscle performance in isolated mouse soleus muscle after recovery from elevated temperature. NEW & NOTEWORTHY Whether elevated temperature affects glycogen biogenesis and contractile performance of isolated slow-twitch muscle is not known. Here we show that after a bout of repeated contractions in isolated mouse soleus muscle at 25°C, increasing muscle temperature during recovery to 35°C blocked glycogen accumulation compared with recovery at 25°C. Surprisingly, during a subsequent bout of repeated contractions at 25°C, the rate of fatigue was not different between groups after recovery at the two temperatures.

The cTnT response to acute exercise at the onset of an endurance training program: evidence of exercise preconditioning?

Exercise induces a cardioprotective effect referred to as "preconditioning". Whether the preconditioning impacts upon the cardiac troponin T (cTnT) response to subsequent exercise bouts is unclear. This study investigated the effects of an initial exercise bout, a second exercise bout 48h later, as well as subsequent exercise every 48h for 4 days or a single identical exercise bout after 8 days of inactivity gap on cTnT response to acute exercise. Twenty-eight sedentary overweight young women were randomly assigned to either six bouts of exercise each separated by 48h or three bouts of exercise with 48h between the first two bouts and 8 days between the second and third bouts. All exercise bouts were identical (60% [Formula: see text], 200kJ) and the total testing period (10 days) was the same for both groups. cTnT was assessed before and after the 1st, 2nd, and final exercise bouts. cTnT increased (129%, P < 0.05) after the first bout of exercise in both groups (peak post-exercise cTnT, median [range], ngl-1: 3.43[< 3.00-27.26]) with no between-group differences in the response. The second exercise bout had no significant (P > 0.05) effect on post-exercise cTnT (< 3.00[< 3.00-21.96]). The final exercise bout resulted in an increase (190%, P < 0.05) in cTnT (4.35[< 3.00-13.05]) in both groups. A single bout exercise resulted in a temporary blunting of cTnT response to acute exercise 48h later. The effect of exercise preconditioning was not preserved, regardless of whether followed by repeated exercise every 48h or a cessation of exercise for 8 days.

Seven consecutive days of remote ischaemic preconditioning improves cutaneous vasodilatory capacity in young adults.

Remote ischaemic preconditioning (RIPC), induced by brief bouts of ischaemia followed by reperfusion, confers vascular adaptations that protect against subsequent bouts of ischaemia; however, the effect of RIPC repeated over several days on the human microcirculation is unknown. Using skin as a model, microvascular function was assessed at a control and a NO-inhibited area of skin before 1day after and 1week after administering seven consecutive days of repeated RIPC on the contralateral arm. Maximal vasodilatation was increased by ∼20-50% following 7days of repeated RIPC, and this response remained elevated 1week after stopping RIPC; however, NO-mediated vasodilatation was not affected by the RIPC stimulus. These data indicate that repeated RIPC augments maximal vasodilatation, but the underlying mechanism for this improvement is largely independent of NO. This finding suggests a role for other endothelium-derived mediators and/or for endothelium-independent adaptations with repeated RIPC. Remote ischaemic preconditioning (RIPC), induced by intermittent periods of ischaemia followed by reperfusion, confers cardiovascular protection from subsequent ischaemic bouts. RIPC increases conduit and resistance vessel function; however, the effect of RIPC on the microvasculature remains unclear. Using human skin as a microvascular model, we hypothesized that cutaneous vasodilatory (VD) function elicited by localized heating would be increased following repeated RIPC. Ten participants (23± 1years, 6 males, 4 females) performed RIPC for seven consecutive days. Each daily RIPC session consisted of 4 repetitions of 5min of arm blood flow occlusion interspersed by 5min reperfusion. Before, 1day after and 1week after the 7days of RIPC, two microdialysis fibres were placed in ventral forearm skin for continuous infusion of Ringer solution or 20mM l-NAME. Red blood cell flux was measured by laser Doppler flowmetry at each fibre site during local heating (Tloc = 39°C) and during maximal VD elicited by heating (Tloc = 43°C) and 28mM sodium nitroprusside infusion. Data were normalized to cutaneous vascular conductance (flux/mmHg). Seven days of RIPC did not alter the nitric oxide (NO) contribution to the VD response to local heating (P> 0.05). However, the maximal VD was augmented (Pre: 2.5± 0.2, Post: 3.8± 0.5flux/mmHg; P< 0.05) and remained elevated 1week post RIPC (3.3± 0.4flux/mmHg; P< 0.05). Repeated RIPC improves maximal VD but does not affect NO-mediated VD in the cutaneous microvasculature. This finding suggests that other factors may explain the vasodilatory adaptations that occur following repeated RIPC.

The stiffness response of type IIa fibres after eccentric exercise-induced muscle damage is dependent on ACTN3 r577X polymorphism

The aim of the study was to determine the effect of α-actinin-3 (ACTN3) deficiency (XX) on muscle damage induced by an eccentric exercise bout. In this purpose, 4 RR and 4 XX individuals performed an intensive eccentric knee flexion exercise on an isokinetic dynamometer. Muscle biopsies, blood and pain scores were taken before and after the exercise to determine the extent of the exercise-induced damage and the effect of the ACTN3 R577X polymorphism. Maximal isometric strength of the quadriceps and single fibre properties were compared before and after the exercise. The drop in maximal isometric strength of the quadriceps at 45° knee flexion following the eccentric exercise bout was on average 37% 24 h post-exercise. The decrease in force was also apparent in isolated type IIa fibres (8%; P = 0.02), but not in type I fibres (P = 0.88). Creatine kinase and myoglobin plasma levels increased in all participants at least by 55% and 87%, respectively (P < 0.05). In addition, mRNA levels of markers for muscle regeneration and muscle remodelling increased after the eccentric exercise (P < 0.05), however, independently from ACTN3 R577X genotype. The mRNA level of nuclear factor of activated T-cells 1 (NFATc1) decreased after the eccentric exercise only in XX genotypes (P < 0.05). The stiffness of type IIa, but not type I muscle fibres increased only in RR individuals after the eccentric exercise (P < 0.05). While no major effect of α-actinin-3 deficiency on susceptibility to muscle damage was found acutely, the increased stiffness response in fast RR fibres might be a protection mechanism from muscle damage during a subsequent eccentric exercise bout.

Basal fatty acid oxidation increases after recurrent low glucose in human primary astrocytes

Aims/hypothesisHypoglycaemia is a major barrier to good glucose control in type 1 diabetes. Frequent hypoglycaemic episodes impair awareness of subsequent hypoglycaemic bouts. Neural changes underpinning awareness of hypoglycaemia are poorly defined and molecular mechanisms by which glial cells contribute to hypoglycaemia sensing and glucose counterregulation require further investigation. The aim of the current study was to examine whether, and by what mechanism, human primary astrocyte (HPA) function was altered by acute and recurrent low glucose (RLG).MethodsTo test whether glia, specifically astrocytes, could detect changes in glucose, we utilised HPA and U373 astrocytoma cells and exposed them to RLG in vitro. This allowed measurement, with high specificity and sensitivity, of RLG-associated changes in cellular metabolism. We examined changes in protein phosphorylation/expression using western blotting. Metabolic function was assessed using a Seahorse extracellular flux analyser. Immunofluorescent imaging was used to examine cell morphology and enzymatic assays were used to measure lactate release, glycogen content, intracellular ATP and nucleotide ratios.ResultsAMP-activated protein kinase (AMPK) was activated over a pathophysiologically relevant glucose concentration range. RLG produced an increased dependency on fatty acid oxidation for basal mitochondrial metabolism and exhibited hallmarks of mitochondrial stress, including increased proton leak and reduced coupling efficiency. Relative to glucose availability, lactate release increased during low glucose but this was not modified by RLG. Basal glucose uptake was not modified by RLG and glycogen levels were similar in control and RLG-treated cells. Mitochondrial adaptations to RLG were partially recovered by maintaining euglycaemic levels of glucose following RLG exposure.Conclusions/interpretationTaken together, these data indicate that HPA mitochondria are altered following RLG, with a metabolic switch towards increased fatty acid oxidation, suggesting glial adaptations to RLG involve altered mitochondrial metabolism that could contribute to defective glucose counterregulation to hypoglycaemia in diabetes.

Femoral Artery Blood Flow and Microcirculatory Perfusion During Acute, Low-Level Functional Electrical Stimulation in Spinal Cord Injury.

Functional electrical stimulation (FES) may help to reduce the risk of developing macrovascular and microvascular complications in people with spinal cord injury. Low-intensity FES has significant clinical potential because this can be applied continuously throughout the day. This study examines the acute effects of low-intensity FES using wearable clothing garment on vascular blood flow and oxygen consumption in people with spinal cord injury. This was a cross-sectional observation study. Eight participants with a motor complete spinal cord injury received four 3-min unilateral FES to the gluteal and hamstring muscles. Skin and deep femoral artery blood flow and oxygen consumption were measured at baseline and during each bout of stimulation. Femoral artery blood flow increased by 18.1% with the application of FES (P = 0.02). Moreover, femoral artery blood flow increased further during each subsequent block of FES (P = 0.004). Skin perfusion did not change during an individual block of stimulation (P = 0.66). Skin perfusion progressively increased with each subsequent bout (P < 0.001). There was no change in femoral or skin perfusion across time in the nonstimulated leg (all P > 0.05). Low-intensity FES acutely increased blood flow during stimulation, with a progressive increase across subsequent FES bouts. These observations suggest that continuous, low-intensity FES may represent a practical and effective strategy to improve perfusion and reduce the risk of vascular complications.

Repeated Exposure to Taekwondo Combat Modulates the Physiological and Hormonal Responses to Subsequent Bouts and Recovery Periods.

Bridge, CA, Sparks, SA, McNaughton, LR, Close, GL, Hausen, M, Gurgel, J, and Drust, B. Repeated exposure to taekwondo combat modulates the physiological and hormonal responses to subsequent bouts and recovery periods. J Strength Cond Res 32(9): 2529-2541, 2018-This study examined the physiological and hormonal responses to successive taekwondo combats using an ecologically valid competition time structure. Ten elite male international taekwondo competitors (age 19 ± 3 years) took part in a simulated championship event. The competitors performed 4 combats that were interspersed with different recovery intervals (63 ± 4, 31 ± 3 and 156 ± 5 minutes, respectively). Heart rate (HR) was measured during the combats and venous blood samples were obtained both before and after each combat to determine the plasma metabolite and hormone concentrations. The plasma noradrenaline (21.8 ± 12.8 vs. 15.0 ± 7.0 nmol·l) and lactate (13.9 ± 4.2 vs. 10.5 ± 3.2 mmol·l) responses were attenuated (p < 0.05) between combat 1 and 4. Higher (p < 0.05) HR responses were evident in the final combat when compared with the earlier combats. Higher (p < 0.05) resting HR (139 ± 10 vs. 127 ± 12 b·min), plasma lactate (3.1 ± 1.2 vs. 2.0 ± 0.7 mmol·l), glycerol (131 ± 83 vs. 56 ± 38 μmol·l) and nonesterified free fatty acid (0.95 ± 0.29 vs. 0.71 ± 0.28 mmol·l) concentrations were measured before combat 3 compared with combat 1. Repeated exposure to taekwondo combat using an ecologically valid time structure modulates the physiological and hormonal responses to subsequent bouts and recovery periods. Strategies designed to assist competitors to effectively manage the metabolic changes associated with the fight schedule and promote recovery between the bouts may be important during championship events.

Ca2+ Signals in Astrocytes Facilitate Spread of Epileptiform Activity.

Epileptic seizures are associated with increased astrocytic Ca2+ signaling, but the fine spatiotemporal kinetics of the ictal astrocyte–neuron interplay remains elusive. By using 2-photon imaging of awake head-fixed mice with chronic hippocampal windows we demonstrate that astrocytic Ca2+ signals precede neuronal Ca2+ elevations during the initial bout of kainate-induced seizures. On average, astrocytic Ca2+ elevations preceded neuronal activity in CA1 by about 8 s. In subsequent bouts of epileptic seizures, astrocytes and neurons were activated simultaneously. The initial astrocytic Ca2+ elevation was abolished in mice lacking the type 2 inositol-1,4,5-trisphosphate-receptor (Itpr2−/−). Furthermore, we found that Itpr2−/− mice exhibited 60% less epileptiform activity compared with wild-type mice when assessed by telemetric EEG monitoring. In both genotypes we also demonstrate that spreading depression waves may play a part in seizure termination. Our findings imply a role for astrocytic Ca2+ signals in ictogenesis.

Manipulating graded exercise test variables affects the validity of the lactate threshold and [Formula: see text

BackgroundTo determine the validity of the lactate threshold (LT) and maximal oxygen uptake () determined during graded exercise test (GXT) of different durations and using different LT calculations. Trained male cyclists (n = 17) completed five GXTs of varying stage length (1, 3, 4, 7 and 10 min) to establish the LT, and a series of 30-min constant power bouts to establish the maximal lactate steady state (MLSS). was assessed during each GXT and a subsequent verification exhaustive bout (VEB), and 14 different LTs were calculated from four of the GXTs (3, 4, 7 and 10 min)—yielding a total 56 LTs. Agreement was assessed between the highest measured during each GXT () as well as between each LT and MLSS. and LT data were analysed using mean difference (MD) and intraclass correlation (ICC).ResultsThe value from GXT1 was 61.0 ± 5.3 mL.kg-1.min-1 and the peak power 420 ± 55 W (mean ± SD). The power at the MLSS was 264 ± 39 W. from GXT3, 4, 7, 10 underestimated by ~1–5 mL.kg-1.min-1. Many of the traditional LT methods were not valid and a newly developed Modified Dmax method derived from GXT4 provided the most valid estimate of the MLSS (MD = 1.1 W; ICC = 0.96).ConclusionThe data highlight how GXT protocol design and data analysis influence the determination of both and LT. It is also apparent that and LT cannot be determined in a single GXT, even with the inclusion of a VEB.

Natural selection and outbreeding depression suggest adaptive differentiation in the invasive range of a clonal plant.

Analyses of phenotypic selection and demography in field populations are powerful ways to establishing the potential role of natural selection in shaping evolution during biological invasions. Here we use experimental F2 crosses between native and introduced populations of Mimulus guttatus to estimate the pattern of natural selection in part of its introduced range, and to seek evidence of outbreeding depression of colonists. The F2s combined the genome of an introduced population with the genome of either native or introduced populations. We found that the introduced × introduced cross had the fastest population growth rate owing to increased winter survival, clonality and seed production. Our analysis also revealed that selection through sexual fitness favoured large floral displays, large vegetative and flower size, lateral spread and early flowering. Our results indicate a source-of-origin effect, consistent with outbreeding depression exposed by mating between introduced and native populations. Our findings suggest that well-established non-native populations may pay a high fitness cost during subsequent bouts of admixture with native populations, and reveal that processes such as local adaptation in the invasive range can mediate the fitness consequences of admixture.

The Effect of a Curved Non-Motorized Treadmill on Running Gait Length, Imbalance and Stride Angle.

Running on a non-motorized, curved-deck treadmill is thought to improve gait mechanics. It is not known, though, whether the change in gait carries over to running on a motorized treadmill on level ground. To determine the effect of running on a curved non-motorized treadmill (CNT) on gait characteristics, measured during a subsequent bout of running on a traditional motorized treadmill (TMT), sixteen healthy college-aged participants, aged (mean ± SD) 20.4 ± 1.6 years, volunteered to have their gait analyzed while running on a TMT and CNT. After familiarization with, and a warm-up on, both treadmills, each subject completed five 4-min bouts of running, alternating between traditional motorized and curved non-motorized treadmills: TMT-1, CNT-1, TMT-2, CNT-2, and TMT-3. Variables of interest included step length (m), stride length (m), imbalance score (%), and stride angle (°), and were measured using Optogait gait analysis equipment. We found differences in gait characteristics among TMT-1, TMT-2, and TMT-3, which can be attributed to running on the CNT. The results show that running on a CNT resulted in significant changes in gait characteristics (step length, stride length, imbalance score and stride angle). These findings suggest that running on a CNT can significantly influence running gait.

Somatostatin Receptor II Antagonism Improves Glucagon Counterregulatory Responses to Recurrent Hypoglycemia in Male Sprague-Dawley Rats

Glucagon (GCN) helps prevent hypoglycemia when blood glucose levels drop; however, recurrent hypoglycemia attenuates GCN counterregulation to subsequent bouts of hypoglycemia. As somatostatin normally inhibits GCN secretion, we tested the hypothesis that a somatostatin receptor type 2 antagonist (SSTR2a), PRL-2903, improves GCN responses attenuated by recurrent hypoglycemia in healthy rats. Healthy male Sprague-Dawley rats (n=22) were made hypoglycemic on three consecutive days (days 1-3, blood glucose 1.7-2.2 mmol/L for ∼2 h) via exogenous insulin administration (10-, 8- and 5- U/kg of Humulin-R on days 1-3, respectively). GCN levels during hypoglycemia on day 3 were significantly lower than on day 1 (117±47 pg/mL vs. 184±77 [mean±SD] pg/mL; P=0.001), highlighting the role of recurrent hypoglycemia in counterregulatory failure. On day 4, rats were treated with either PRL-2903 (10 mg/kg IP; n=13) or vehicle (n=9) 1 h prior to the induction of hypoglycemia with 5 U/kg of R-insulin. GCN levels during hypoglycemia (i.e., glucose ≤3.5 mmol/L) were 2.5-fold higher (109±55 vs. 44±26 pg/mL; P=0.004) compared to vehicle, and time to reach hypoglycemia was 3.2-fold longer (64±45 vs. 20±10 min; P =0.001), with PRL-2903 pre-treatment. Interestingly, C-peptide levels were also lower (P=0.001) with PRL-2903 (0.35±0.22 ng/mL), compared to vehicle (0.63±0.21 ng/mL), inferring a lower insulin secretion during hypoglycemia with PRL-2903 treatment. In conclusion, our data suggests that SSTR2a improves GCN responses following recurrent hypoglycemia, and that this improvement may be associated with a reduction in insulin secretion in healthy rats. Therefore, SSTR2a treatment may be a useful therapeutic approach to improve GCN counterregulatory responses to hypoglycemia. Disclosure M. Riddell: Speaker's Bureau; Self; Medtronic. Consultant; Self; Eli Lilly and Company, JAEB Center For Health Research, Xeris Pharmaceuticals, Inc.. Research Support; Self; Insulet Corporation. Speaker's Bureau; Self; Insulet Corporation. Advisory Panel; Self; Sanofi. Speaker's Bureau; Self; Ascensia Diabetes Care. Stock/Shareholder; Self; Zucara Theraputics. Other Relationship; Self; JDRF. M. Jahangiriesmaili: None. E.R. Mandel: None. C.A. Greenberg: None. A.M. Pasieka: None. T. Teich: None. O. Chan: None. R.T. Liggins: Employee; Self; Zucara Therapeuytics, Inc..

Respiratory Impedance Enhances Recovery and Performance During Repeated Bouts of High-Intensity Exercise

Impedance threshold devices (ITD) were initially developed to maintain blood pressure during battlefield trauma. By creating a greater negative intrathoracic pressure, venous return is enhanced (Ryan et al., 2008). Convertino et al. (2005) found that spontaneous breathing through an ITD increased stroke volume and cardiac output during the initial 10 s of standing from a squat position and was an effective countermeasure against hypotension initiated by the squat-to-stand test. PURPOSE: This study evaluated the efficacy of using an ITD during recovery following three consecutive 30 s, high-intensity exercise bouts on a bicycle ergometer. METHODS: Fifteen participants (11 men, 4 women, 24 ± 1 years-of-age, M ± SEM) completed two exercise conditions separated by at least 7 days: control (no ITD) and breathing through an ITD during recovery (ResQGARD®, Advanced Circulatory Systems, Eden Prairie, MN). Each exercise bout was performed with a resistance set at 60 g/kg body weight followed by a 4 min recovery between bouts. RESULTS: Ratings of perceived exertion ranged between 7.9 and 9.5 on the Borg category-ratio scale during the three exercise bouts with ratings slightly lower during the ITD condition (F(1, 54) = 4.774, p < .05). There was a significant interaction effect for ratings of perceived recovery (F(3, 40) = 2.980, p < .05) with participants indicating they felt better recovered after bout 3 when using the ITD. There was also a significant interaction effect for mean power (F(2, 28) = 3.842, p < .05) with power better maintained during bout 3 when using the ITD (416 ± 32 W vs. 400 ± 34 W for the control condition). In contrast, there were no significant effects of the ITD on peak power or blood lactate compared to the control condition. CONCLUSION: Using an ITD between repeated bouts of high-intensity exercise may help individuals feel better recovered and, thus, able to maintain higher mean power during subsequent exercise bouts.

Arachidonic acid supplementation transiently augments the acute inflammatory response to resistance exercise in trained men.

Strenuous exercise can result in skeletal muscle damage, leading to the systemic mobilization, activation, and intramuscular accumulation of blood leukocytes. Eicosanoid metabolites of arachidonic acid (ARA) are potent inflammatory mediators, but whether changes in dietary ARA intake influence exercise-induced inflammation is not known. This study investigated the effect of 4 wk of dietary supplementation with 1.5 g/day ARA ( n = 9, 24 ± 1.5 yr) or corn-soy oil placebo ( n = 10, 26 ± 1.3 yr) on systemic and intramuscular inflammatory responses to an acute bout of resistance exercise (8 sets each of leg press and extension at 80% one-repetition maximum) in previously trained men. Whole EDTA blood, serum, peripheral blood mononuclear cells (PMBCs), and skeletal muscle biopsies were collected before exercise, immediately postexercise, and at 2, 4, and 48 h of recovery. ARA supplementation resulted in higher exercise-stimulated serum creatine kinase activity [incremental area under the curve (iAUC) P = 0.046] and blood leukocyte counts (iAUC for total white cells, P < 0.001; neutrophils: P = 0.007; monocytes: P = 0.015). The exercise-induced fold change in peripheral blood mononuclear cell mRNA expression of interleukin-1β ( IL1B), CD11b ( ITGAM), and neutrophil elastase ( ELANE), as well as muscle mRNA expression of the chemokines interleukin-8 ( CXCL8) and monocyte chemoattractant protein 1 ( CCL2) was also greater in the ARA group than placebo. Despite this, ARA supplementation did not influence the histological presence of leukocytes within muscle, perceived muscle soreness, or the extent and duration of muscle force loss. These data show that ARA supplementation transiently increased the inflammatory response to acute resistance exercise but did not impair recovery. NEW & NOTEWORTHY Daily arachidonic acid supplementation for 4 wk in trained men augmented the acute systemic and intramuscular inflammatory response to a subsequent bout of resistance exercise. Greater exercise-induced inflammatory responses in men receiving arachidonic acid supplementation were not accompanied by increased symptoms of exercise-induced muscle damage. Although increased dietary arachidonic acid intake does not appear to influence basal inflammation in humans, the acute inflammatory response to exercise stress is transiently increased following arachidonic acid supplementation.

RECOVERY AND FATIGABILITY FOLLOWING MAXIMAL AND SUBMAXIMAL EXERCISE

Measures of cardiorespiratory function during recovery from an exercise challenge may provide insight into the capacity to perform subsequent bouts of activity. However, the relationship between recovery of cardiorespiratory homeostasis and fatigability during subsequent bouts of activity is not well understood.PurposeTo characterize oxygen consumption (VO2off) kinetics during the recovery following maximal and submaximal exercise and examine the relationship between VO2off kinetics and fatigability during a subsequent bout of submaximal activity.Methods6 healthy subjects (2 male, 4 female; 31.8±4.6 years) completed a maximal cardiopulmonary exercise test followed by a 10‐minute walk test (10‐MW). On a separate day, a submaximal constant work rate test was followed by a 10‐MW. Indices of VO2off kinetics, including the off‐kinetics transition constant (KtO), mean response time (MRT), time constant (τ), VO2 amplitude change (Δamp), and Δamp half‐time (t1/2) were determined. Performance (PF) and perceived (PC) fatigability were scored during each 10‐MW as change in walking speed and change in self‐rated fatigue severity, each normalized the individuals' distance walked. Higher PF and PC scores indicate greater presence of fatigability. Data were analyzed using paired samples t‐test and Pearson's correlation coefficient (r).ResultsMean values of KtO were greater (p&lt;.001) following maximal vs. submaximal exercise (−43.6±18.4 mL/min/s vs. −24.2±17.4 mL/min/s, respectively). No difference was observed for fatigability scores during the 10MW between maximal and submaximal exercise (PF: 0.97±0.15, 1.0±0.09; PC: 3.8±1.5, 3.56±0.88). Following maximal exercise, PF was directly correlated with KtO (r=0.68) and Δamp (r=0.68), while PC was directly correlated with τ (r=0.74). Following submaximal exercise, PF was directly correlated with τ (r=0.76), t1/2 (r=0.91), Δamp (r=0.55), and KtO (r=0.52). PC following submaximal exercise was indirectly correlated with all indices of VO2 off‐kinetics including Δamp (r=−0.60), τ (r=−0.62), t1/2 (r=−0.84), MRT (r=−0.81), and KtO (r=−0.62).ConclusionDespite a greater VO2 amplitude change during maximal compared to moderate exercise, indices of VO2off kinetics suggested an efficient recovery in this sample of healthy individuals, in that neither intensity effected performance nor perceived fatigability. PF scores were directly associated with VO2off kinetics indices following both maximal and submaximal exercise, while PC scores were directly associated with VO2off kinetics only after maximal exercise. Findings of this pilot study may suggest that performance fatigability could reflect the recovery rate of the oxidative metabolic system following cessation of both severe and moderate intensity activity. Results of this study must be delimited to the current sample and cannot be generalized to the population at large.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.