Browsing by Subject "Motor Control"
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Item Arterial Baroreflex Control of Muscle Sympathetic Nerve Activity(2000-07-01) Fadel, Paul Joseph; Peter B. Raven; Michael Smith; Patricia GwirtzFadel, Paul Joseph, Jr., Arterial Baroreflex Control of Muscle Sympathetic Nerve Activity. Doctor of Philosophy (Biomedical Science), July 2000; 100 pp; 3 tables; 10 figures; bibliography. Arterial baroreflex control of sympathetic nerve activity is dependent on afferent nerve activity emanating from both the aortic and carotid baroreceptors. While several investigations have reported that the aortic baroreceptor reflex dominates in the baroreflex control of heart rate in humans, the role of carotid and the aortic baroreceptors in the control of sympathetic nerve activity remains unclear. In addition, the effect of exercise and long term endurance training on baroreflex-sympathetic nerve activity responses requires further definition. Therefore, the purpose of the investigations described within this dissertation was to: i) describe carotid baroreflex (CBR) control of muscle sympathetic nerve activity (MSNA) at rest and during exercise, ii) examine the relative contribution of the carotid and aortic baroreflexes to the overall arterial baroreflex control of MSNA during acute hypotension, and iii) determine the effect of fitness on arterial baroreflex control of MSNA. In the first investigation, we constructed stimulus-response relationships for CBR control of MSNA at rest and during dynamic arm cycling and demonstrated that carotid baroreflex control of MSNA was reset to function at the higher arterial pressures induced by exercise without a change in reflex sensitivity. Thus, we concluded that the carotid baroreflex control of MSNA was preserved during dynamic exercise. In the second investigation, acute hypotension was induced non-pharmacologically by releasing a unilateral arterial thigh cuff (300 Torr) following nine minutes of resting ischemia under two conditions: control (aortic and carotid baroreflex deactivation) and suction (aortic baroreflex deactivation alone). The application of neck suction to negate the CBR during cuff release caused a significant attenuation of the MSNA response and a greater decrease in mean arterial pressure; thereby signifying the importance of the CBR in the control of MSNA and maintenance of arterial blood pressure. However, when the drop in carotid sinus pressure was counteracted with neck suction a significant MSNA response was noted, indicating the dominance of the aortic baroreflex control of MSNA. Furthermore, a comparison between high-fit (HF) and average fit (AF) subjects indicated that despite an augmented baroreflex control of MSNA, HF subjects exhibited a greater decrease in mean arterial pressure compared to AF subjects. Thus, it appeared that although the arterial baroreflex appropriately increased the MSNA response to hypotension, the regulation of blood pressure remained attenuated in the HF subjects. We contend that an impaired control of vasomotion hinders blood pressure regulation in high-fit subjects.Item Dysfunctional Control of Coronary Blood Flow in Renovascular Hypertension(1999-06-01) Kline, Geoffrey Philip; Gwirtz, Patricia A.; Shi, Xiangrong; Raven, Peter B.Kline, Geoffrey Philip, Dysfunctional Control of Coronary Blood Flow in Renovascular Hypertension Doctor of Philosophy (Biomedical Sciences), June 1999, 98 pp, 2 tables, 10 figures, references, 142 titles. This study was designed to determine the effects of renovascular hypertension (RVH) on coronary vasoreactivity in conscious, chronically instrumented dogs. Six dogs were instrumented to measure left ventricular pressure, +dP/dtmax, heart rate, mean aortic pressure, circumflex blood flow (CBF), and cardiac output. In order to examine endothelial-dependent and independent coronary vasodilation, intracoronary injections of actylcholine (Ach), bradykinin (BDK), and sodium nitroprusside (SNP) were studied before and after induction of RVH in the presence and absence of nitric oxide (NO) blockade. After RVH, resting CBF was significantly reduced (P [less than] 0.05). In the normotensive state, NO-blockade significantly reduced the coronary vasodilation to Ach and BDK (P [less than] 0.05), but not SNP. After RVH, the coronary vasodilation to Ach, BDK, and SNP were reduced (P[less than] 0.05). After RVH, NO-blockade further reduced the coronary vasodilation to BDK (P [less than] 0.05), but not Ach. Thus, RVH resulted in an impairment of both endothelial-dependent and –independent coronary vasodilation. It also appears that during RVH the endothelium retains the ability to produce/release NO to some, but not all, stimuli. In order to examine the possibility that β-adrenergic mediated coronary vasodilation is impaired after RVH, intracoronary injections of norepinephrine (NE), isoproterenol (ISO), and terbutaline (TRB) were administered. These drugs all caused dose dependent increases in CBF before and after RVH. After RVH, the coronary vasodilatory responses to NE, ISO and TRB were significantly reduced (P [less than] 0.05). β1-blockade with intracoronary atenolol (1 mg) reduced the ISO-induced increases in CBF and had no effect on TRB responses (P [less than] 0.05). β2-blockade with intracoronary ICI-118,551 (1 mg) reduced the ISO-induced coronary vasodilation and abolished TRB responses (p[less than] 0.05). During β2-blockade, ISO-induced increases in CBF were not different after RVH. Therefore, these data indicate that β1-adrenergic mediated coronary vasodilation is preserved after RVH, whereas, β2-mediated is not. We conclude that 1) RVH results in an impairment of both endothelial-dependent and –independent coronary vasodilation; 2) RVH results in an impairment of β2-adrenergic mediated coronary vasodilation.Item Influence of Thermoregulatory and Nonthermoregulatory Control Mechanisms of Arterial Blood Pressure During Recivert from Exercise in Humans(2001-05-10) Carter, Robert; Michael L. Smith; Robert L. Kaman; Thomas YorioCarter, III Robert, Thermoregulatory and nonthermoregulatory control of arterial pressure during recovery from exercise in humans. Doctor of Philosophy (Biomedical Sciences). May 2001; 153p; 4 tables, 17 figures; 100 titles. The mechanisms of arterial blood pressure control during exercise is well established; however, much less is known about the regulation of arterial blood pressure immediately after intense or prolonged dynamic exercise. Inactive recovery from dynamic exercise is associated with cessation of the primary exercise stimuli from the brain (central command), Skeletal muscle pumping, which contributes to increases in venous return during exercise is also stopped during inactive recovery from exercise. Thus, the skeletal muscle pump and central command each contribute importantly to elevation and maintenance of arterial blood pressure regulation and cerebral blood flow during exercise. When exercise is intense and/or prolonged, the resulting thermal load exacerbates the challenge to maintain arterial blood pressure and cerebral blood flow both during exercise and particularly during recovery from exercise and thereby increases the risk of syncope. Recently, we found that the skeletal muscle pump plays a major role in arterial blood pressure control during recovery from brief (3 min), mild (60% of maximal HR) exercise in which there was no thermal load. However, how the mechanisms of arterial pressure regulation operate during recovery from intense or prolonged exercise when a thermal load occurs is unknown. Therefore, the purpose of the investigations described herein, was to quantify the mechanisms of the carotid baroreflex function, central command, and the skeletal muscle pump when a thermal stress occurs on arterial blood pressure regulation during recovery from exercise in humans. In addition, differences in arterial blood pressure regulation in women and men during recovery from exercise were addressed in women and men. To investigate these mechanisms, we investigated the carotid-cardiac baroreflex function, cardiovascular, and thermoregulatory responses in volunteer subjects during inactive and active recovery from prolonged exercise improved the function of the baroreflex by increasing the functional reserve of the reflex to buffer against hypotensive stimuli. Our data also suggest that thermoregulatory factors contribute to decreases in MAP after inactive recovery from exercise. In addition, the metabolic state of skeletal muscle during longer duration exercise (15 min) may contribute to these responses during inactive recovery from exercise. These results support the hypothesis that thermal stress contributes to the rapid decreases in arterial blood pressure during inactive recovery following dynamic exercise. To investigate gender differences in arterial pressure regulation during recovery from exercise, we compared 11 women and 8 men during 3 min of exercise and 5 min of inactive and active recovery from exercise. Interestingly, at 1 minute after exercise, MAP decreased less during inactive recovery in men when compared to women. This difference was due to greater decreases in SV and less increase in TPR during inactive recovery from exercise in women compared to men. MAP decreased less during active recovery in men when compared to women. These findings suggest that women may have increased risk of post-exercise orthostatic hypotension and that active recovery from exercise may reduce this risk.Item Leucine-Enkephalin and Sympathetic Control of Heart Rate(2001-12-01) Stanfill, Amber; Caffrey, James L.; Downey, H. Fred; Shi, XiangrongStanfill, Amber A., Leucine-enkephalin and Sympathetic Control of Heart Rate. Master of Science (Biomedical Sciences), December, 2001, 51 pp., 1 table, 4 figures, references, 48 titles. The following study examined the role of leucine-enkephalin in the sympathetic regulation of the cardiac pacemaker. Leucine-enkephalin (0.3 mM) was administered, by microdialysis into the interstitium of the sinoatrial node in 10 mongrel dogs in conjunction with either sympathetic nerve stimulation or infused norepinephrine. In study one, the right cardiac sympathetic nerves were isolated as they exit the stellate ganglion and stimulated to produce graded (low, 20-30; high 40-50 bpm) increases in heart rate. Once stimulation frequencies were determined, leucine-enkephalin (0.3mM) was added to the dialysis inflow and perfused at 5: 1/min thereafter. The sympathetic stimulations were repeated after 5 and 20 min exposure to leucine-enkephalin. The resulting increases in heart rate during sympathetic stimulation were attenuated at both low (18.2 ±1.3 to 11.4 ±1.4 bpm) and high (45 ±1.5 to 22.8 ±1.5 bpm) frequency stimulation. The degree of inhibition was nearly identical after 20 minutes exposure providing no evidence for a progressively evolving response and for desensitization. Vagal function was also evaluated at 5 and 20 min by stimulating the right cervical vagus at 1 and 3 Hz. Leucine-enkephalin reduced the vagal bradycardia approximately 50% at both time intervals. The administration of the delta-selective opioid antagonist, naltrindole, restored only one third of the sympathetically medicated tachycardia. The same dose of naltrindole completely reversed the coincident vagolytic of leucine-enkephalin. These observations suggested that the sympatholytic effect was either non-opioid or mediated by a different opioid receptor subtype. Study two was conducted to determine if the sympatholytic effect was prejunctional and post-junctional in character. Norepinephrine was added to the dialysis inflow into the SA node in a concentration (6-9 μM) sufficient to produce an intermediate increase in heart rate. The average increase in heart rate was 35.2 ±1.8 bpm. Leucine-enkephalin was then combined with norepinephrine and sympathetic and parasympathetic responses were recorded at 5-min intervals for 20 minutes. The tachycardia mediated by added norepinephrine was unaltered by leucine-enkephalin or the subsequent addition of naltrindole. At the same time intervals, vagal control of heart rate was reduced by more than 50% and then completely restored by naltrindole. When combined with observations in study one, the data support the conclusion that the local nodal sympatholytic effect of leucine-enkephalin was the result of a reduction in the effective interstitial concentration of norepinephrine and not the result of a post-junctional interaction between leucine-enkephalin and norepinephrine.Item Local Enkephalins Modulate Vagal Control of Heart Rate(2001-05-01) Jackson, Keith E.; James L. Caffrey; H. Fred Downey; Michael W. MartinJackson, Keith E., Local Enkephalins Modulate Vagal Control of Heart Rate. Doctor of Philosophy (Biomedical Sciences), May 2001; 112pp; 7 tables; 22 figures; bibliography, 99 titles. Endogenous opioids, such as enkephalins, were first investigated for their ability to modulate pain. A body of evidence now supports opioid actions in many facets of regulation, including the cardiovascular system. Our laboratory is particularly interested in the ability of opioids to modulate autonomic function. Specifically, the role of the endogenous encephalin, methionine-enkephalin-arginine-phenylalanine (MEAP) was investigated to determine its ability to modulate parasympathetic function in the canine. To investigate MEAP’s response in the sinoatrial (SA) node a novel application of microdialysis was employed, whereby microdialysis was employed, whereby microdialysis probes were fabricated as described by Dr. David Van Wylen (38), and implanted in the SA node. After implantation of the probe, there was a significant attenuation of vagal function during the nodal application of MEAP. Specifically, vagally mediated bradcardia was reduced as compared to control, during the nodal application of MEAP. This inhibition of the vagus by MEAP was blocked by naltrindole, a selective delta antagonist. These data suggested that the vagolytic effects of MEAP were elicited via a delta opioid receptor. To test the hypothesis that MEAP’s effects were elicited through a delta opioid receptor mechanism, selective agonists and antagonists for the opioid receptors were utilized. An attenuation of vagal bradycardia was only observed during the infusion of a very selective delta opioid receptor agonist, deltorphin. A mu and kappa agonist showed no significant differences from control. Deltorphin was observed to elicit vagolytic effects in a similar concentration range as MEAP. However, deltorphin was more efficacious that MEAP. There was a significant attenuation of the deltorphin and MEAP’s vagolytic effects, during the co-infusion of the selective delta antagonist, naltrindole. The mu and kappa antagonists were both ineffective. These data further demonstrate that the observed vagolytic effect is linked to a delta opioid receptor. Endogenous MEAP. A series of experiments were undertaken to determine if endogenous MEAP could be demonstrated in the SA node and is so, was it similarly vagolytic. A preconditioning-like protocol was performed to produce intermittent local nodal ischemia to increase the local concentration of endogenous MEAP. The resulting MEAP was measured and was observed to be elevated during the periods of local nodal ischemia and return to control during reperfusion. Contrary to expectations an augmentation of vagal function was observed, during vagal stimulation. The augmented vagal bradycardia was only observed during ischemia, when MEAP was elevated and returned to control during each subsequent reperfusion. Therefore, there was a correlation between elevated MEAP concentrations and augmented vagal bradycardia. The delta antagonist, naltrindole, prevented the augmented vagal response, during nodal ischemia Glibenclamide, a selective KATP channel blocker, partially reversed the augmented vagal response. These data confirm that delta opiate receptors are involved in the augmented vagal bradycardia and that the mechanism may involve the activation of a KATP channel.Item Mechanisms of Post-Apneic Symathoinhibition in Humans(2002-08-01) Swift, Nicolette Muenter; Michael Smith; David Barker; John R BurkMuenter Swift, Nicolette, Mechanisms of Post-Apneic Sympathoinhibition in Humans. Doctor of Philosophy (Biomedical Sciences), August, 2002, 110 pp., 14 figures, references. Apnea is accompanied by a concomitant rise in arterial pressure and muscle sympathetic nerve activity (MSNA), the latter primarily due to chemoreflex stimulation and possibly the lack of sympathoinhibitory input from pulmonary stretch receptors. The progressive sympathoexcitation during apnea suggests a possible overriding of arterial baroreflex sympathoinhibitory input to sympathoregulatory centers by apnea-induced sympathoexcitatory mechanisms. Nevertheless, it is unknown whether apnea attenuates baroreflex control of MSNA. Apnea termination is accompanied by a profound and immediate sympathoinhibition, the mechanisms of which are unclear; however, potential mediators include normalization of blood gases (i.e. chemoreflex unloading), the lung inflation reflex, and arterial baroreflex stimulation. Therefore, the purpose of the current studies was to: i) determine the contribution of chemoreflex unloading to post-apneic sympathoinhibition, ii) determine the contribution of the lung inflation reflex to post-apneic sympathoinhibition, and iii) determine whether carotid baroreflex control of MSNA is altered by apnea and its termination. The first study compared MSNA during post-apneic administration of room air versus a gas mixture designed to maintain the subjects’ end-apneic alveolar gas levels. Regardless of post-apneic gas administration, post-apneic MSNA was at or below baseline pre-apneic levels; thus; chemoreflex unloading does not contribute to post-apneic sympathoinhibition. Furthermore, quantification of post-apneic MSNA associated only with the low lung volume phase of respiration, when sympathoinhibitory input from the lung inflation reflex is minimal, demonstrated that post-apneic sympathoinhibition persists even during the low lung volume phase of respiration, when sympathoinhibitory input from the lung inflation reflex is minimal, demonstrated that post-apneic sympathoinhibition persists even during the low lung volume phase of respiration. Therefore, the lung inflation reflex does not appear to be the primary mediator of post-apneic sympathoinhibition. The second study utilized neck suction (NS) and neck pressure (NP) to assess carotid baroreflex function during and following sleep apnea. The sympathoinhibitory response to -60 Torr NS was maintained throughout apnea; conversely, the sympathoexcitatory response to +30 Torr NP was attenuated for nearly one minute post-apnea. Thus, carotid baroreflex control of MSNA is not altered by apnea but is transiently attenuated by apnea termination. We propose that the carotid baroreflex-MSNA function curve resets rightward and upward during apnea. Return of the function curve to baseline upon apnea termination may partly explain the reduced MSNA response to NP post-apnea.Item Neural Control of the Carotid Baroreflex During Exercise(2000-05-01) Gallagher, Kevin Matthew; Peter B. Raven; Stephen R. Grant; H. Fred DowneyGallagher, Kevin Matthew, Neural Control of the Carotid Baroreflex During Exercise. Doctor of Osteopathic Medicine/Doctor of Philosophy (Biomedical Sciences), May 2000; 151 pages; 13 tables; 19 figures; bibliography; 161 titles. Carotid baroreflex (CBR) function is reset upward and rightward to the prevailing blood pressure during dynamic and static exercise. Feedforward central neural inputs (central command) and negative feedback from skeletal muscle (exercise pressor reflex) both contribute to the resetting. The purpose of this investigation was to identify the individual roles of central command and the exercise pressor reflex in the resetting of the CBR during dynamic and static exercise. First, it was necessary to determine which receptor group that comprises the exercise pressor reflex, chemically-sensitive (chemoreceptors) or mechanically-sensitive (mechanoreceptors) receptors, was primarily involved in the regulation of the cardiovascular system. We observed the cardiovascular responses during exercise to individual action of the chemoreceptors and the mechanoreceptors. We demonstrated an increased mean arterial pressure (MAP) response to mechanoreceptor activation that was not identified during chemoreceptor stimulation. This finding suggested that the mechanoreflex was the primary exercise pressor mediated of arterial blood pressure during exercise. To identify the role of central command on CBR resetting, a second investigation increased central command by partial neuromuscular blockade during dynamic and static exercise. Resetting of CBR control of heart rate (carotid-cardiac; CSP-HR) and MAP (carodtid-vasomotor; CSP-MAP) during control exercise was further reset upward and rightward by increased central command without alterations in sensitivity. In conclusion, central command, a feedforward mechanism, was actively involved in the resetting of the CBR during exercise. To investigate the role of the exercise pressor reflex on CBR function, a third investigation activated by the exercise pressor reflex with the application of medical anti-shock trousers (MAS) during dynamic and static exercise. From control exercise, carotid-vasomotor function was further reset upward and rightward by the application of MAS trousers while CSP-HR function was only reset rightward. Sensitivity of the CSP-MAP and CSP-HR function curves were unaltered. The negative feedback mechanism of exercise pressor reflex, primarily mediated by mechanoreceptors, appeared to act as a modulator of CBR resetting during exercise.Item Regulation of Carotid Baroreflex Resetting During Arm Exercise(1999-06-01) Querry, Ross G.; Peter B. Raven; Patricia Gwirtz; Michael SmithQuerry, Ross G., Regulation of Carotid Baroreflex Resetting during Arm Exercise. Doctor of Philosophy (Biomedical Sciences), June 1999, 100 pp., 4 tables, 12 figures, bibliography, 56 titles. Cardiovascular responses to exercise are modulated by the integration of the central nervous system and afferent information from arterial baroreflexes and working skeletal muscle. Investigations have shown that during exercise, the carotid baroreflex (CBR) is reset in proportion to the exercise intensity. The role of the central nervous system contribution to the CBR resetting has not been elucidated. Investigations of CBR function in the animal model consistently report CBR variables such as maximal gain that are different than those reported in humans. These discrepancies may be due in part to methodological limitations in the neck pressure/neck suction (NP-NS) technique used to investigate the isolated CBR function in humans. To accurately examine the internal stimulus from the NP-NS maneuver, subjects were instrumented with a percutaneous catheter to record tissue pressure at the carotid sinus during five-second and rapid pulse NP-NS protocols. Carotid baroreflex function curves were analyzed with and without transmission correction of the carotid sinus pressure (CSP). Results indicated that positive pressure was more fully transmitted (~83%) than negative pressure (~65%) during the five-second-pulse, but not the rapid pulse protocol. Correction of the CSP in either protocol resulted in significant increases in CBR maximal gain and threshold and a reduced saturation pressure. These methodological refinements were then utilized to investigate the role of central command on CBR function during exercise. Subjects performed static and rhythmic handgrip exercise before and after regional anesthesia. Carotid baroreflex curves were analyzed at rest and during exercise before and after blockade at the same absolute workload. Muscle weakness from the blockade required an increased effort to maintain control tension. Heart rate, arterial pressure and perceived exertion during exercise were increased following blockade. During control exercise the CBR function curves were reset upward and rightward compared to rest with a further parallel shift during exercise with blockade. The operating point of the CBR was reset along with the centering point, but did not show the divergence toward the threshold pressure that had been previously described during dynamic exercise. The results support the proposal that central command was a primary mechanism for the resetting of the carotid baroreflex during exercise, but may not be the primary mechanism in the resetting of the operating point of the reflex.Item Role of Adenosine in Acute Hibernation of Guinea-Pig Myocardium(1995-08-01) Gao, Zhi-Ping; H. Fred Downey; James L. Caffrey; Patricia A. GwirtzGao, Zhi-Ping, Role of Adenosine in Acute Hibernation of Guinea-Pig Myocardium Doctor of Philosophy (Biomedical Sciences), August, 1995; 111 pp; 3 tables; 15 figures, bibliography, 158 titles. Myocardial hibernation is a state of depressed contractile function and energy demand during chronic ischemia. When coronary flow is restored, depressed contractile function can partially or completely recover to the pre-ischemic level, and ischemic injury of the myocardium in not evident. This project tested the hypothesis that endogenous adenosine mediates hibernation in guinea-pig myocardium. Isolated working guinea-pig hearts, perfused with glucose fortified Krebs-Henseleit buffer, were subjected to global low-flow ischemia. Left ventricular performance and cytosolic energy level were assessed. Lactate and purine nucleotides were measured in venous effluent. Heart were perfused with [U-14C]glucose to investigate the role of adenosine on glucose metabolism in myocardium. Left ventricular function in untreated hearts decreased by 80% and remained stable during ischemia, and completely recovered upon reperfusion. Neither adenosine receptor blockade with 8-p-sulfophenyl theophylline (8-SPT; 20 μM) nor ecto 5’-nucleotidase inhibitor αβ-methylene adenosine 5’-diphosphonate (AOPCP; 50μM) affected left ventricular function either ischemia or during reperfusion. Cytosolic energy level fell by 67% at 10 min ischemia in untreated hearts, but subsequently recovered to the pre-ischemic level despite continued ischemia. Adenosine receptor blockade increased cytosolic energy level at 10 min ischemia relative to untreated hearts, but blunted the subsequent rebound of phosphorylation potential. Moreover, 8-SPT doubled ischemic lactate release. Adenosine receptor blockade also increased glucose uptake during pre-ischemia and hypoperfusion, but did not stimulate glucose oxidation. Crossover plots of glycolytic intermediates revealed that phosphofructokinase, a key rate-controlling step in glycolysis, was activated by adenosine receptor blockade in both pre-ischemic and hibernating myocardium. We conclude that 1) activation of adenosine receptors results in recovery of cytosolic energy level of moderately ischemic working myocardium, but this energetic recover is not solely responsible for post-ischemic contractile recovery; 2) endogenous adenosine attenuates anaerobic glycolysis during myocardial hibernation by blunting phosphofructokinase activity.Item Sympathetic Responses to Dynamic Arm Ergometry in Humans(2001-05-11) Wasmund, Stephen Lee; Patricia A. Gwirtz; Peter B. Raven; H. Fred DowneyWasmund, Stephen L, Sympathetic Responses to Dynamic Arm Ergometry. Doctor of Philosophy (Biomedical Sciences), May 2001; 96 pp; 1 table; 15 figures; bibliography. Cardiovascular control during exercise is of obvious importance due to the need for an increase in cardiac output and maintenance of blood pressure when metabolic demands increase. While investigations during exercise have been conducted for some time, and much is known about the responses to dynamic exercise, the understanding of the signals that elicit the cardiovascular changes, particularly as mediated by sympathetic nerve activity (SNA) is incomplete. Sympathetic nerve activity plays an important role during exercise by causing vasoconstriction in non-working vascular beds, probably causing vasoconstriction in the vascular beds of working muscles to partially counteract the profound vasodilation caused by locally produced metabolites and by stimulating the heart to increase contractility and heart rate. It is possible to directly measure electrical activity in sympathetic nerves supplying the vasculature of skeletal muscles, however few investigations have reported on this activity during strenuous dynamic exercise. The investigations described in this dissertation extend the understanding of muscle sympathetic nerve responses to dynamic exercise. The first investigation evaluated SNA during a graded arm ergometry test to near volitional fatigue and demonstrated that increases in SNA began to occur at approximately 40% of peak exercise and then increase in a linear fashion until exercise is stopped. This relation is more closely linked to relative workload rather than heart rate as previously suggested. We also sought to determine the relationship between the increase in SNA and the ventilator threshold, hypothesizing that the two would occur at similar times, and concluded that the exercise protocol utilized did not elicit a distinct breakpoint in ventilation. However, a ventilator threshold did occur in two subjects and there appeared to be an accelerated increase in SNA. The second investigation assessed the dynamics of SNA, blood pressure and heart rate responses during the onset and termination of dynamic arm ergometry at mild, moderate and intense workloads to determine the relationship between changes in sympathetic nerve activity and blood pressure. When analyzing data every 10 seconds we determined that modest increases in SNA tend to occur at the onset of exercise in most subjects, but this response did not reach significance. This finding suggests that a neural mechanism, likely central command, plays a minor role in the initial activation of SNA, although this is probably attenuated or overridden by cardiopulmonary reflex mediated sympathoinhibition as has been previously proposed. The delay (30 s) in frank sympathetic nerve activation during strenuous exercise strongly suggests that a delayed signal, probably muscle metaboreceptor stimulation, is the primary stimulus for activation of SNA. At the termination of 5 minutes of exercise SNA, blood pressure and heart rate all decreased significantly below peak values within 10 seconds. We propose that metabolites rapidly drop below a threshold level that allows SNA to decrease significantly towards baseline values. A rapid control mechanism, such as central command or mechanoreceptor stimulation, might also play an important role in returning SNA towards resting values following exercise. We conclude that SNA remains active throughout relatively strenuous dynamic exercise, and that multiple control mechanisms are likely responsible for its control during the onset and termination of exercise.Item THE CURRENT USE OF VIRTUAL ENVIRONMENTS FOR ASSESSMENT AND TREATMENT OF AUTISM SPECTRUM DISORDER(2014-03) Krishnan, Meena M.; Miller, Haylie L.; Bugnariu, Nicoleta L.Virtual environments (VEs) are an emerging technology used to assess and treat people with Autism Spectrum Disorders (ASD). VEs can be presented on a traditional computer monitor or in a more immersive setting on a large screen or in a room. This review investigates large screen VEs, which include interactive and non-interactive interfaces. Individuals can engage in varying levels of interaction with the VE by using a computer mouse, using a touch screen monitor, or moving their body in space to control virtual representations of themselves. People with ASD have differing levels of deficits in social skills, movement awareness/coordination, and behavioral regulation. In order to accurately draw conclusions about real-world functioning, researchers must produce naturalistic but repeatable experiences, where key variables can be controlled and systematically manipulated. The use of VEs may enable researchers and clinicians to achieve this balance in the assessment and treatment of ASD. Purpose (a): We aim to provide a comprehensive review of immersive large screen Virtual Environments (VEs), and to determine whether immersive VEs are effective for assessing and treating behavioral, social and motor symptoms of Autism Spectrum Disorder (ASD). Understanding applications of VEs will facilitate better understanding of the benefits of controlling naturalistic experiences balanced with the ability to repeat experiences the same way every time. This will assist researchers and clinicians in their ability to diagnose and treat symptoms of ASD related to social skills, movement awareness/coordination, and behavioral regulation. Methods (b): Six search engines were used: PubMed, Scopus, Ebsco via Medline, CINHAL, PsycINFO, and PsycARTICLES. Search dates were July–October 2013. Keywords used were: Autism, Autism Spectrum Disorder, ASD, Asperger, Pervasive Developmental Disorder, PDD, virtual reality, VR, virtual environment, and augmented reality. 71 articles were found. Articles were sorted according to level of immersion. 7 articles met the final criteria for immersive VEs with large screen presentation. Results (c): The majority of studies involving VEs used a traditional computer monitor display, rather than an immersive setting. Studies using large screen presentation of VEs focused primarily on gross motor movements (Cai et al., 2013; Cook et al., 2013; Cheng et al., 2012; Greffou et al., 2012) or a combination of motor and social skills (Jung et al., 2006). Two studies focused on social skills and engagement with the VE (Mineo et al., 2009; Wallace et al., 2010). In 6 of the 7 studies reviewed, participants with ASD were successfully either treated or assessed using VE technology. However, there is a clear need for more research evaluating cognitive and behavioral abilities in ASD using immersive VEs. Conclusions (d): Immersive VE is a promising tool for use in studies of children and adults with ASD. The use of immersive VEs for assessment/treatment of ASD is still new, and therefore not well-understood. However, several studies have demonstrated that both interactive and non-interactive VEs are an effective and engaging tool for assessing motor and social skills in ASD across a broad age range, and may be effective for delivering interventions. This technology also has potential for use as an assessment tool in non-verbal ASD populations (Cai et al., 2013). This growing body of work highlights the potential utility of VEs for assessment and treatment of ASD.