Submaximal Responses Research Articles

A Pilot Study to Examine the Effects of a Mindfulness-Based Stress-Reduction and Relaxation Program on Levels of Stress Hormones, Physical Functioning, and Submaximal Exercise Responses

A Pilot Study to Examine the Effects of a Mindfulness-Based Stress-Reduction and Relaxation Program on Levels of Stress Hormones, Physical Functioning, and Submaximal Exercise Responses

Alanine-scanning mutagenesis in the signature disulfide loop of the glycine receptor alpha 1 subunit: critical residues for activation and modulation.

The glycine receptor enables the generation of inhibitory postsynaptic currents at synapses via neurotransmitter-dependent activation. These receptors belong to the ligand-gated ion channel gene superfamily, in which all members are comprised of five subunits, each of which possesses a signature 13-residue disulfide loop (Cys loop) in the extracellular domain. In this study, we used alanine-scanning mutagenesis of the residues between C138 and C152 of the Cys loop of the glycine receptor alpha1 subunit to identify residues critical for receptor activation and allosteric modulation. Mutation of L142, F145, or P146 to alanine produced decreases in the potency, maximal amplitude, and Hill coefficient for currents elicited by glycine and impaired receptor activation by the agonist taurine. These residues, along with D148, are positionally conserved in the family of LGIC subunits. Mutation at several other positions had little or no effect. The inhaled anesthetics halothane and isoflurane potentiate submaximal agonist responses at wild-type receptors, via an allosteric site. The mutations L142A, F145A, P146A, and D148A abolished positive modulation by these anesthetics, in some cases revealing a small inhibitory effect. A molecular model of the glycine receptor alpha1 subunit suggests that the Cys loop is positioned in a region of the receptor at the interface between the extracellular and transmembrane domains and that the critical functional residues identified here lie along the face of a predominantly hydrophobic surface. The present data implicate the Cys loop as an important functional moiety in the process of glycine receptor activation and allosteric regulation by anesthetics.

A Physiological Comparison of Synchronous and Asynchronous Hand Cycling

The purpose of this study was to compare submaximal physiological responses (oxygen uptake, ventilation, heart rate) and gross mechanical efficiency between synchronous and asynchronous hand cycling at different cadences. Thirteen non-disabled men (22.4 +/- 1.6 yr) performed two submaximal exercise tests on a treadmill, using synchronous and asynchronous crank settings in counter balanced order. Tests were performed using a commercially available hand cycle unit that was attached to a hand rim wheelchair. Each test consisted of five 5-min exercise bouts at 36, 47, 55, 65, and 84 rpm. ANOVA for repeated measures showed a significant effect of crank mode (p < 0.001) and cadence (p < 0.001), as well as an interaction effect between both (p < 0.01). Physiological responses were lower, and efficiency higher, in synchronous versus asynchronous hand cycling at all cadences. Post-hoc analysis of the (overall) effect of cadence showed significantly higher physiological responses and lower efficiency at the higher (84 vs. 65 rpm and 65 vs. 55 rpm) and lower (36 vs. 47 rpm) cadences. The interaction effect indicates that the effect of crank mode was dependent on cadence, showing a larger difference between synchronous and asynchronous hand cycling at 84 vs. 65 rpm and at 36 vs. 47 rpm. It is concluded that, in contrast to previous results in arm crank ergometry, synchronous hand cycling is less strenuous and more efficient than asynchronous hand cycling.

Frequency of Verbal Encouragement Effects Sub-Maximal Exertional Perceptions During Exercise Testing in Young Adult Women

0915 PURPOSE: The purpose of this investigation was to determine the effect of frequency of verbal encouragement on ratings of perceived exertion (RPE) at sub-maximal exercise test intensities in young (18 to 21 year old) healthy females. METHODS: Thirty-six healthy females were randomly assigned to either a control group (no verbal encouragement), a 20 second encouragement group (verbal encouragement every 20s) or a 60 second encouragement group (verbal encouragement every 60s). All subjects completed two maximal exercise tests, a baseline test (without verbal encouragement) and an experimental test, using the Bruce treadmill protocol. Subjects were oriented to the OMNI-Walk/Run Scale which was used to assess RPE during the last 20 seconds of each exercise stage. RESULTS: Groups did not differ in age, body composition or baseline maximal aerobic power. Sub-maximal RPE-Overall was significantly lower for the 20 second encouragement group during stages II and III than baseline response (2.2 ± .75 vs. 3.5 ± 1.24, P < 0.01; 4.6 ± 1.0 vs. 6.1 ± 1.37, P < 0.01, respectively). Sub-maximal RPE-Overall responses were also significantly lower for the 60 second encouragement group during stage II and stage III than the baseline condition (2.25 ± .86 vs. 3.4 ± 1.0, P < 0.01; 5.0 ± 1.13 vs. 6.2 ± 1.33, P < 0.05, respectively). Submaximal RPE-Leg responses were significantly lower for the 20 second encouragement group during stages II and III than baseline response (2.3 ± 1.07 vs. 3.5 ± 1.16, P < 0.05; 4.6 ± 1.37 vs. 6.1 ± 1.6, P < 0.05, respectively). In addition, verbal encouragement every 60 seconds resulted in a significantly lower RPE-Legs response during stage II than in the baseline condition (2.3 ± .77 vs. 3.5 ± 1.0, P < 0.01). No between group differences were observed for any sub-maximal VO2 and HR response. There were no between or within group differences in maximal oxygen consumption and treadmill performance time. CONCLUSIONS: The findings suggest that the mechanisms underlying the psychological impact of verbal encouragement during sub-maximal exercise are complex but may include a dampening of unpleasant stimuli as they travel to the sensory cortex for coding and ultimately conscious expression as an exertional estimate.

Aerobic Exercise Adaptations Of Summer-training In Well-trained Male And Female Adolescent Distance Runners

1414 Maximal oxygen uptake (VO2max) and running economy (RE) are important determinants of endurance running performance. In preparation for a competitive cross-country season, most high-school athletes train during the summer months. However, the effects of this form of endurance training on VO2max and RE are largely unknown. PURPOSE: This study examined alterations in VO2max and RE along with submaximal blood lactate concentration ([BLa]) before (Pre) and after (Post) summer training in a group of well-trained high school runners. METHODS: Seven females (15.8 ± 1.1yrs) and 11 males (17.0 ± 0.9 yrs) underwent treadmill testing. Submaximal exercise responses were measured during steady-state exercise at 7.0 and 8.0 mph, and VO2max was measured by a graded exercise test to exhaustion. Data was collected 2–3 weeks after the subjects' competitive track season at the onset of summer training (Pre), and 1–2 weeks prior to the first competitive cross-country meet (Post). The data were analyzed using repeated measures ANOVA's. RESULTS: Pre and Post VO2max data in males was 70.9 ± 3.5 and 72.9 ± 4.5 ml/kg/min. In females VO2max was 57.9 ± 5.1 and 57.1 ± 4.6 ml/kg/min during the same two testing periods. The interaction and time effects were not significant; however, VO2max in males was greater (p < 0.05) than in females. Pre RE at 7.0 and 8.0 mph was 40.9 ± 2.5 and 46.4 ± 2.7 ml/kg/min in males and 40.7 ± 1.9 and 46.2 ± 1.9 ml/kg/min in females, respectively. Post RE at 7.0 and 8.0 mph decreased (p < 0.05) and was 40.4 ± 2.5 and 45.8 ± 2.8 ml/kg/min in males and 39.8 ± 2.9 and 44.9 ± 3.4 ml/kg/min in females, respectively. Differences between gender and all interactions were not significant. At 7.0 mph [BLa] in males were 1.7 ± 0.3 mmol/L Pre and 1.9 ± 0.4 mmol/L Post. At 8.0 mph [BLa] was 1.8 ± 0.3 mmol/L Pre and 1.7 ± 0.5 mmol/L Post. In females, [BLa] at 7.0 mph were 2.2 ± 0.5 and 1.8 ± 0.3 mmol/L in Pre and Post, respectively. At 8.0 mph [BLa] in females was 3.4 ± 1.1 mmol/L Pre and was 2.7 ± 0.7 mmol/L Post. [BLa] was lower (p < 0.05) in males, decreased over time (p < 0.05) with the decrease from Pre to Post being greater in females than males (p < 0.05). CONCLUSIONS: Pre-season distance running does not appear to increase VO2max in high-school cross-country runners, but does improve RE. The change in [BLa] from Pre to Post was greater in females, however the lack of change in males was most likely attributed to their extremely low initial [BLa] levels and higher level of fitness. Supported by the Office of Academic Research and Sponsored Programs at Ball State University and the Gatorade Sports Science Institute

Aerobic Exercise Adaptations Of Summer-training In Well-trained Male And Female Adolescent Distance Runners

1414 Maximal oxygen uptake (VO2max) and running economy (RE) are important determinants of endurance running performance. In preparation for a competitive cross-country season, most high-school athletes train during the summer months. However, the effects of this form of endurance training on VO2max and RE are largely unknown. PURPOSE: This study examined alterations in VO2max and RE along with submaximal blood lactate concentration ([BLa]) before (Pre) and after (Post) summer training in a group of well-trained high school runners. METHODS: Seven females (15.8 ± 1.1yrs) and 11 males (17.0 ± 0.9 yrs) underwent treadmill testing. Submaximal exercise responses were measured during steady-state exercise at 7.0 and 8.0 mph, and VO2max was measured by a graded exercise test to exhaustion. Data was collected 2–3 weeks after the subjects' competitive track season at the onset of summer training (Pre), and 1–2 weeks prior to the first competitive cross-country meet (Post). The data were analyzed using repeated measures ANOVA's. RESULTS: Pre and Post VO2max data in males was 70.9 ± 3.5 and 72.9 ± 4.5 ml/kg/min. In females VO2max was 57.9 ± 5.1 and 57.1 ± 4.6 ml/kg/min during the same two testing periods. The interaction and time effects were not significant; however, VO2max in males was greater (p < 0.05) than in females. Pre RE at 7.0 and 8.0 mph was 40.9 ± 2.5 and 46.4 ± 2.7 ml/kg/min in males and 40.7 ± 1.9 and 46.2 ± 1.9 ml/kg/min in females, respectively. Post RE at 7.0 and 8.0 mph decreased (p < 0.05) and was 40.4 ± 2.5 and 45.8 ± 2.8 ml/kg/min in males and 39.8 ± 2.9 and 44.9 ± 3.4 ml/kg/min in females, respectively. Differences between gender and all interactions were not significant. At 7.0 mph [BLa] in males were 1.7 ± 0.3 mmol/L Pre and 1.9 ± 0.4 mmol/L Post. At 8.0 mph [BLa] was 1.8 ± 0.3 mmol/L Pre and 1.7 ± 0.5 mmol/L Post. In females, [BLa] at 7.0 mph were 2.2 ± 0.5 and 1.8 ± 0.3 mmol/L in Pre and Post, respectively. At 8.0 mph [BLa] in females was 3.4 ± 1.1 mmol/L Pre and was 2.7 ± 0.7 mmol/L Post. [BLa] was lower (p < 0.05) in males, decreased over time (p < 0.05) with the decrease from Pre to Post being greater in females than males (p < 0.05). CONCLUSIONS: Pre-season distance running does not appear to increase VO2max in high-school cross-country runners, but does improve RE. The change in [BLa] from Pre to Post was greater in females, however the lack of change in males was most likely attributed to their extremely low initial [BLa] levels and higher level of fitness. Supported by the Office of Academic Research and Sponsored Programs at Ball State University and the Gatorade Sports Science Institute

Involvement of Sodium in Early Phosphatidylserine Exposure and Phospholipid Scrambling Induced by P2X7 Purinoceptor Activation in Thymocytes

Extracellular ATP (ATP(ec)), a possible effector in thymocyte selection, induces thymocyte death via purinoceptor activation. We show that ATP(ec) induced cell death by apoptosis, rather than lysis, and early phosphatidylserine (PS) exposure and phospholipid scrambling in a limited thymocyte population (35-40%). PS externalization resulted from the activation of the cationic channel P2X7 (formerly P2Z) receptor and was triggered in all thymocyte subsets although to different proportions in each one. Phospholipid movement was dependent on ATP(ec)-induced Ca(2+) and/or Na(+) influx. At physiological external Na(+) concentration, without external Ca(2+), PS was exposed in all ATP(ec)-responsive cells. In contrast, without external Na(+), physiological external Ca(2+) concentration promoted a submaximal response. Altogether these data show that Na(+) influx plays a major role in the rapid PS exposure induced by P2X7 receptor activation in thymocytes.

Effects of Caffeine on Submaximal Responses to Exercise in Children

Effects of Caffeine on Submaximal Responses to Exercise in Children

Effects of Caffeine on Submaximal Responses to Exercise in Children

Effects of Caffeine on Submaximal Responses to Exercise in Children

Submaximal and Maximal Cardiorespiratory Responses of Leg Wheeling and Arm Wheeling a New Wheelchair Prototype

The present study examined the cardiorespiratory responses to propelling a new wheelchair prototype using a unique type of leg wheeling (LW) that allowed the subjects to propel the wheelchair using bilateral knee extension/flexion. Comparisons were made to arm wheeling (AW) and to treadmill running (TR) using a standard maximal oxygen consumption test to exhaustion. Nine female able-bodied subjects performed three incremental submaximal exercise bouts followed by exercise to exhaustion using AW and LW. The results showed that LW was more efficient than AW, as evidenced by lower cardiorespiratory effort at the same submaximal intensity during LW, and a lower physiological cost index (PCI—change in heart rate divided by velocity of wheeling) during maximal workloads. LW also elicited significantly higher peak cardiorespiratory values than AW but not TR. The cardiorespiratory variables measured during LW were also highly reliable. In conclusion, this unique form of LW was more efficient than AW during submaximal and maximal exercise.

Vasopressin stimulates insulin release from islet cells through V1b receptors: a combined pharmacological/knockout approach.

Vasopressin receptor subtype(s) responsible for stimulation of insulin release from pancreatic beta cells were investigated by using subtype-selective antagonists and mice that were genetically lacking either V1a or V1b receptors. Arginine vasopressin (AVP) increased insulin release from isolated mouse islet cells in a concentration-dependent manner, with a submaximal response at 100 nM. Reverse transcription-polymerase chain reaction (RT-PCR) analysis detected V1b and oxytocin, but not V1a or V2, receptor transcripts in mouse islet cells. We characterized the recently synthesized vasopressin receptor subtype antagonists (2S)1-[(2R 3S)-(5-chloro-3-(2-chlorophenyl)-1-(3,4-dimethoxybenzene-sulfonyl)-3-hydroxy-2,3-difydro-1H-indole-2-carbonyl)-pyrrolidine-2-carboxamide] (SR49059), 1-[1-[4-(3-acetylaminopropoxy)benzoyl]-4-piperidyl]-3,4-dihydro-2(1H)-quinolinone (OPC-21268), and (2S,4R)-1-[5-chloro-1-[(2,4-dimethoxyphenyl)sulfonyl]-3-(2-methoxy-phenyl)-2-oxo-2,3-dihydro-1H-indol-3-yl]-4-hydroxy-N,N-dimethyl-2-pyrrolidine carboxamide (SSR149415) using human embryonic kidney 293 cells stably expressing the three cloned mouse vasopressin receptors (V1a, V1b, and V2). A radioligand binding study showed that SR49059 and OPC-21268 potently inhibited [3H]AVP binding to the cloned mouse V1a receptor, with Ki values of 27 and 510 nM, respectively, whereas SSR149415 potently inhibited [3H]AVP binding to the cloned mouse V1b receptor with a Ki value of 110 nM. The inhibitory effects of vasopressin antagonists on AVP-induced insulin release correlate well with the rank order of potency to inhibit [3H]AVP binding to the V1b receptor; pancreatic islet cells were significantly inhibited by SSR149415 but not by SR49059 or OPC-21268. Furthermore, the AVP effect on insulin release was entirely lost in mice lacking the V1b receptor but was preserved in mice lacking the V1a receptor. Our study, which combined pharmacological and knockout approaches, clearly demonstrates that vasopressin-stimulated insulin release from islet cells is mediated via V1b receptors.

Beta2- and beta3-adrenergic receptor polymorphisms and exercise hemodynamics in postmenopausal women.

We sought to determine whether common genetic variations at the beta2 (beta2-AR, Gln27Glu) and beta3 (beta3-AR, Trp64Arg) adrenergic receptor gene loci were associated with cardiovascular (CV) hemodynamics during maximal and submaximal exercise. CV hemodynamics were assessed in 62 healthy postmenopausal women (20 sedentary, 22 physically active, and 20 endurance athletes) during treadmill exercise at 40, 60, 80, and 100% maximal O2 uptake using acetylene rebreathing to quantify cardiac output. The beta2-AR genotype and habitual physical activity (PA) levels interacted to significantly associate with arteriovenous O2 difference (a-vDO2) during submaximal exercise (P = 0.05), with the highest submaximal exercise a-vDO2 in sedentary women homozygous for the beta2-AR Gln allele and no genotype-dependent differences in submaximal exercise a-vDO2 in physically active and athletic women. The beta2-AR genotype also was independently associated with a-vDO2 during submaximal (P = 0.004) and approximately 100% maximal O2 uptake exercise (P = 0.006), with a 1.2-2 ml/100 ml greater a-vDO2 in the Gln/Gln than in the Glu/Glu genotype women. The beta3-AR genotype, independently or interacting with habitual PA levels, was not significantly associated with any CV hemodynamic variables during submaximal or maximal exercise. Thus it appears that the beta2-AR genotype, both independently and interacting with habitual PA levels, is significantly associated with a-vDO2 during exercise in postmenopausal women, whereas the beta3-AR genotype does not appear to be associated with any maximal or submaximal exercise CV hemodynamic responses in postmenopausal women.

Relationship between exercise systolic blood pressure and left ventricular geometry in overweight, mildly hypertensive patients.

To examine the association between the graded exercise systolic blood pressure (SBP) response and left ventricular (LV) geometric structure in patients with untreated mild hypertension. The study included 80 sedentary, overweight patients (43 female and 37 male) with unmedicated high normal blood pressure or stage 1-2 hypertension. An echocardiogram was used to determine LV mass and the relative wall thickness (RWT) in relation to the chamber dimension. Participants performed a maximal graded exercise test, and the SBP was recorded at workloads of 2, 4 and 6 metabolic equivalents and at peak exercise. Separate statistical models were used to determine the influence of LV mass indexed for height(2.7) (LVMIh) and RWT on submaximal exercise SBP and peak exercise SBP, controlling for resting SBP, age, gender, ethnicity and body mass index. A greater RWT was associated with a higher submaximal SBP level (P = 0.038). Neither LVMIh (P = 0.989) nor the interaction of RWT and LVMIh (P = 0.787) were related to the submaximal SBP. None of the main or interaction effects of RWT and LVMIh were associated with the peak exercise SBP level. Increases in RWT were associated with higher submaximal exercise SBP responses in a sample of overweight, unmedicated hypertensives. These results suggest that RWT is an important determinant of the association between cardiac mass and exercise SBP response.

Cardiorespiratory fitness and walking ability in subacute stroke patients

Kelly JO, Kilbreath SL, Davis GM, Zeman B, Raymond J. Cardiorespiratory fitness and walking ability in subacute stroke patients. Arch Phys Med Rehabil 2003;84:1780–5. Objectives To evaluate the cardiorespiratory fitness of subacute stroke patients and to determine whether reduced fitness is associated with gait performance. Design Descriptive, cross-sectional study. Setting Rehabilitation hospital. Participants Seventeen patients in an inpatient rehabilitation unit who had mild to moderate gait impairments after a recent (≤7wk) stroke. All subjects could walk at least 3m alone or with an aid but with no standby assistance. Interventions Not applicable. Main outcome measures Peak and submaximal cardiorespiratory responses were measured during semirecumbent leg cycling exercise. Walking velocity and endurance were assessed with 10-m and 6-minute walk tests, respectively. Results Peak oxygen uptake (V o 2peak) was 1.15±0.36L/min, which was only 50% of the V o 2peak reported in the literature for a healthy, age-matched group. Maximal walking velocity (1.02±0.28m/s) and endurance (294.1±120.2m) were also approximately 50% of an aged-matched healthy group. Pearson product-moment correlations revealed that 6-minute walking endurance was strongly associated with self-selected walking velocity ( R=.91) and measures of peak cardiorespiratory fitness ( R=.84). Conclusions Cardiorespiratory fitness was markedly impaired within 7 weeks after a stroke. Although muscle weakness and loss of coordination are the primary impairments that affect gait after a stroke, impaired cardiorespiratory fitness may secondarily affect gait performance by limiting walking endurance. To address this secondary impairment, current rehabilitation interventions can incorporate assessment of cardiorespiratory fitness status and aerobic exercise training for persons after stroke.

Calcium-triggered Membrane Fusion Proceeds Independently of Specific Presynaptic Proteins

Complexes of specific presynaptic proteins have been hypothesized to drive or catalyze the membrane fusion steps of exocytosis. Here we use a stage-specific preparation to test the roles of SNAREs, synaptotagmin, and SNARE-binding proteins in the mechanism of Ca2+-triggered membrane fusion. Excess exogenous proteins, sufficient to block SNARE interactions, did not inhibit either the Ca2+ sensitivity, extent, or kinetics of fusion. In contrast, despite a limited effect on SNARE and synaptotagmin densities, treatments with high doses of chymotrypsin markedly inhibited fusion. Conversely, low doses of chymotrypsin had no effect on the Ca2+ sensitivity or extent of fusion but did alter the kinetic profile, indicating a more direct involvement of other proteins in the triggered fusion pathway. SNAREs, synaptotagmin, and their immediate binding partners are critical to exocytosis at a stage other than membrane fusion, although they may still influence the triggered steps.

Virtual Reality Serves as a Support Technology in Cardiopulmonary Exercise Testing

The purpose of this study was to develop a virtual cycling system and examine the influence of virtual reality (VR) on test performance during clinical exercise testing. We aimed to compare the physiological responses of the cardiovascular and ventilatory systems during incremental exercise testing with or without VR, and to measure VR effects on the ratings of perceived exertion (RPE) and cycling duration throughout the test. Twelve healthy senior citizens (ten men and two women) with a mean age of 74.5-4.7 years participated in the study. The codes of behavior for this study included a maximum graded exercise tolerance test, a submaximal endurance VR exercise, and a submaximal endurance non-VR exercise. A friction-braked cycle ergometer was used to conduct the exercise tests. For the subject's movement speed to create an appropriate environment flow on the display screen, the bike was connected to a personal computer. The cardiorespiratory and hemodynamic parameters were evaluated at both peak and submaximal exertion. The results show that the VR versus non-VR programs did not differ on submaximal and peak exercise responses during the cycling test. However, significant differences were observed between the mean values for cycling duration, distance, and energy consumption. The difference between RPE curves for VR and non-VR protocols revealed promising results within 45 min. of cycling (Breslow test, p = .06); however, no statistical significance was achieved at the test termination (log rank test, p =.17). In conclusion, this study found that the maintenance of endurance, the increase in target intensity, and total energy consumption in exercise programs may be assisted by introducing VR technology. In addition, the activities taking place in virtual environments can be performed in complete safety.

Heart rate and behavior are regulated independently of corticosterone following diverse acute stressors

Captive European starlings ( Sturnus vulgaris) were subjected to five acute stressors: a visual stressor (strobe light), an auditory stressor (music), and disturbance by three different humans; their accustomed caretaker, an antagonist (the experimenter), and a novel human. Heart rate (HR), behavioral, and corticosterone (CORT) responses to each stressor were simultaneously recorded. The visual stressor elicited a significantly lower maximal HR response [∼550 beats per minute (bpm)] that returned to basal levels (335 bpm) more quickly than the HR increases elicited by any of the four other stressors (∼700 bpm). These data suggest that the degree of novelty may alter the magnitude and duration of the HR response. Behaviorally, both the auditory stressor and the human antagonist caused a significant decrease in preening behavior without subsequent increases in activity, beak wiping (a behavioral indicator of displaced aggression), or bouts of feeding and/or drinking. In contrast to the stressor-specific differences in HR and behavior, all five acute stressors elicited similar sub-maximal CORT responses, suggesting the presence of a standardized CORT response to sudden, acute stimuli in wild captive starlings. The data indicate that starlings modulate HR, CORT, and behavioral responses depending upon the stressor, but that these three pathways are regulated independently.

THE RELATIONSHIP BETWEEN SUBMAXIMAL TREADMILL RESPONSES AND SIX-MINUTE WALK DISTANCE IN COPD PATIENTS

PURPOSE To investigate the relationships between changes in submaximal exercise responses and six-minute walk distance (6MWD) in chronic obstructive pulmonary disease (COPD) patients following a three-month exercise program. METHODS Patients (N=116) participated in an exercise program consisting of walking and upper-body resistance training conducted 3 times per week. Submaximal treadmill exercise responses [oxygen consumption (VO2), heart rate (HR), and minute ventilation (VE)] and 6MWD were measured at baseline and three months. Submaximal treadmill exercise responses were calculated using the second minute of the first (S1) and second (S2) stages of the Modified Naughton treadmill protocol. RESULTS There was a significant increase (p < .05) in 6MWD (196.76 ± 193.54 m) after intervention. There were significant decreases in VO2 (S1: −.5 ± 1.6 mL/kg/min), HR (S1: −4.24 ± 10.73 b/min; S2: −3.34 ±12.74 b/min), and VE (S1: −1.2 ± 3.7 L/min; S2: −1.58 ± 4.18 L/min) after three months of treatment. Changes in 6MWD were not significantly correlated (p > .05) with changes in VO2 (S1: r = −.16; S2: r = −.03), HR (S1: r = −.51; S2: r = .02), or VE (S1: r = −.11; S2: r = .06). CONCLUSION These findings suggest that changes in submaximal treadmill exercise responses are independent of changes in 6MWD.

DICHLOROACETATE IMPROVES PARAMETERS OF AEROBIC FUNCTION IN PATIENTS WITH DEFECTS IN MITOCHONDRIAL ENERGY METABOLISM

PURPOSE To determine the acute and chronic effects of dichloroacetate (DCA) on maximal (MAX) and submaximal (SUB) exercise responses in patients with inborn errors of mitochondrial energetics. METHODS Patients (n=11) completed a MAX treadmill test ∼ 3.5 hr after ingesting 25 mg/kg DCA or placebo (PL). The following day, a 15 min SUB exercise bout (∼65% VO2peak) was completed while taking the same treatment. After a one-day washout period, MAX and SUB were repeated crossed-over to the other study treatment (acute phase). Gas exchange variables were measured continuously throughout all tests. Heart rate (HR), blood pressure (BP), blood lactate (LA), and ratings of perceived exertion (RPE) were obtained at 0, 3 and 10 min following MAX, and 5, 10 and 15 min during SUB. Both MAX and SUB were repeated after three months of daily DCA or PL. After a two-week washout period, patients switched to the alternate treatment for an additional three months and completed a final MAX and SUB (chronic phase). RESULTS There was a significant treatment effect for chronic DCA vs. PL for VO2peak (21.59 ±8.21 vs. 20.51 ±8.2 ml.min−1.kg−1.,p = 0.016). Average LA was lower (1.89 ±1.03 vs. 2.37 ±1.39 mmol/L,p = 0.009), but average HR was higher (129.0 ±12.7 vs. 123.8 ±12.6 b/min,p = 0.032), for DCA vs. PL during SUB during the acute phase. The overall mean LA level during SUB was significantly lower for DCA vs. PL (1.93 ±1.15 vs. 2.25 ±1.33 mmol/L,p = 0.019), regardless of testing period. This occurred despite exercising at similar workloads (73.3 ±10.5 vs. 69.1 ±8.3% VO2peak for DCA and PL). CONCLUSIONS Aerobic capacity is greater following chronic DCA compared to similar PL treatment. Furthermore, DCA reduces blood LA levels during SUB exercise. Thus, DCA treatment improves markers of MAX and SUB aerobic function in patients with inborn errors of mitochondrial energetics.

5-HT4 receptors contribute to the motor stimulating effect of levosulpiride in the guinea-pig gastrointestinal tract.

The dopamine D2 receptor antagonist levosulpiride is a substituted benzamide derivative, whose gastrokinetic properties are exploited clinically for the management of functional dyspepsia. However, for other benzamide derivatives, such as cisapride and mosapride, agonism towards serotonin 5-HT4 receptors is considered the main mechanism leading to gastrointestinal prokinesia. To assess whether levosulpiride is able to activate 5-HT4 receptors in the guinea-pig isolated gastrointestinal tract. Circular muscle strips from gastric antrum, and colonic longitudinal muscle strips were used to detect electrically stimulated neurogenic contractions. The effect of levosulpiride was assessed in the absence and presence of GR125487, a selective 5-HT4 receptor antagonist. Furthermore, potential interaction of levosulpiride with 5-HT3 receptors and tissue cholinesterases was assessed in unstimulated ileal longitudinal muscle-myenteric plexus preparations. Antral and colonic strip contractions were cholinergic/tachykinergic in nature. Micromolar concentrations of levosulpiride potentiated submaximal responses, through a mechanism competitively antagonized by GR125487 (pKB=9.4). In LMMPs, levosulpiride slightly affected contractions caused by the 5-HT, receptor agonist 2-methyl-5-HT, and had no effect on contractions to exogenous acetylcholine. Our results indicate that levosulpiride acts as a moderate agonist at the 5-HT4 receptor. This property, together with antagonism at D2 receptors, may contribute to its gastrointestinal prokinetic effect.