Browsing by Subject "Exercise Physiology"
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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 Baroreflex Mediated Autonomic Modulation by Acute Pain and Orthostatic Stress(2008-10-01) Raven, Joseph Simon; James Caffrey; Joan Carroll; Robert MalletRaven, Joseph Simon, Baroreflex Mediated Autonomic Modulation by Acute Pain and Orthostatic Stress. Doctor of Philosophy (Integrative Physiology), October 2008, 147 pp.; 23 figures; bibliography; 123 titles. Nociceptive and baroreceptor afferent neurons are implicated as the components responsible for carotid baroreceptor reflex (CBR) resetting. The purpose of this dissertation was to identify the effect of cold induced pain, and cardiopulmonary baroreceptor (CPBR) unloading accompanied by pain, on CBR resetting. First, the relationships between cold induced pain to cardiovascular responses, pain perception, and muscle sympathetic nerve activity (MSNA) were investigated. Questions were addressed through use of the cold pressor test (CPT), finger plethysmography, and microneurography. This study demonstrated perceived pain, MSNA, and blood pressure responses to a cold stimulus were reproducible. Furthermore, graded responses observed in mean arterial pressure (MAP) and MSNA directly correlated to the intensity of the pain stimulus. The next study examined cold induced pain on CBR gain and operational point resetting in healthy normotensive subjects. Using similar experimental methodologies to the previous study, the data demonstrated acute pain shifted the CBR operational point toward the lower limiting value of MSNA. These data also confirmed an upward-rightward shift and increased gain of the CBR function curve during pain. Finally, CBR gain and operational point resetting during simultaneous CPBR unloading and cold induced pain in healthy normotensive subjects was addressed. Using the previous experimental paradigm, this investigation revealed CPBR unloading during acute pain did not abolish the shift of the CBR operational point. Thus, the capacity for hypotensive buffering remained enhanced. This study also determined CPBR unloading during acute pain produced higher prevailing blood pressures compared to periods of CPBR unloading alone. In summary: 1)MSNA and cardiovascular responses were tightly coupled to pain. 2) The CPT was a reliable technique for producing repeated sympathoexcitation within a subject. 3) Acute pain increased CBR gain and induced a shift of the CBR operational point. 4) The CBR operational point shift remained in the presence of CPBR unloading, which precipitated increased MAP during hypotensive stimuli. These findings suggested pain improves blood pressure maintenance during central hypovolemic stress.Item Carotid Baroreflex of Leg Vasculature(2004-07-01) Keller, David Melvin; Peter A. Raven; H. Fred Downey; Patricia A. GwirtzKeller, David Melvin, Carotid Baroreflex Control of Leg Vasculature. Doctor of Philosophy (Biomedical Science), July 2004; 110 pp; 5 tables; 10 figures; bibliography. The carotid baroreflex (CBR) exerts control of arterial blood pressure primarily as a result of changes in total vascular conductance. In humans, understanding CBR control of the vasculature supplying a given vascular bed, such as the leg, remains unclear. Furthermore, it appears that metabolic attenuation of sympathetic vasoconstriction may modulate the CBR of the vasculature supplying contracting skeletal muscle during exercise. However, the balance between baroreflex-mediated vasoconstriction and the mechanisms responsible for the metabolic attenuation has not been fully elucidated. Therefore, the purpose of the investigations within this dissertation was to: i) explain CBR control of leg vascular conductance (LVC) and the relationship between changes in LVC and muscle sympathetic nerve activity at rest and during one-legged knee extension exercise, ii) examine the CBR control of the vasculature supplying an exercising leg and a non-exercising leg during exercise, and iii) demonstrate the role of the ATP-sensitive potassium channel in contributing to the metabolic attenuation of CBR-mediated vasoconstriction in the vasculature supplying contracting skeletal muscle. In the first investigation, we demonstrated: i) the stimulus response relationships for CBR control of LVC and MSNA at rest and during two intensities of one-legged knee extension exercise; ii) that CBR control of LVC was preserved during exercise; iii) that the attenuation of CBR-mediated vasoconstriction was no different between 7W and 25W exercise in the vasculature supplying an exercising leg; and iv) that the contribution of changes in LVC to CBR changes in mean arterial pressure was no different from rest to exercise in both the exercising leg and the non-exercising leg. In the second investigation, we examined the role of the ATP-sensitive potassium channel in modulating sympathetically-mediated vasoconstriction at rest and during exercise in the vasculature supplying an exercising leg and a non-exercising leg. The attenuated vasoconstrictor response to the carotid baroreceptor stimulated hypotension observed in the vasculature supplying an exercising leg was partially restored two to four hours after the oral ingestion of glyburide (5mg). This finding indicates that ATP-sensitive potassium channel activation plays a primary role in the effects of functional sympatholysis during leg exercise in humans. We further demonstrated that CBR control of MAP was not altered by oral glyburide administration in healthy subjects.Item Does Osteopathic Manipulative Treatment Improve Dyspnea and Exercise Tolerance Subjects with Stable Chronic Obstructive Pulmonary Disease?(2006-05-01) Pickett, Carolyn M.; Stoll, Scott; Cruser, des Anges; Licciardone, John C.Pickett, Carolyn M., D.O., M.S. Does Osteopathic Manipulative Treatment Improve Dyspnea and Exercise Tolerance in Subjects with Stable Chronic Obstructive Pulmonary Disease? Master of Science (Clinical Research and Education – OMM), May 2006, 54 pages, 10 tables, 4 figures, references 48 titles. Chronic Obstructive Pulmonary Disease (COPD) is the fourth leading cause of death globally and is projected to increase. This highly prevalent and costly disease causes reduced physical and social functioning, and none of the existing medications for COPD seem to modify long-term decline in lung function. COPD patients with the severe dyspnea have more deficits in the health status and energy. Reduced functional status has been significantly correlated with health related quality of life. Osteopathic Manipulative Treatment (OMT) has been suggested for treatment of COPD as early as 1902, some research indicates that OMT may improve dyspnea and exercise tolerance, yet there are few published studies on OMT and COPD. Study goals were to increase scientific knowledge about how OMT may immediately improve dyspnea and exercise tolerance in stable COPD following exertion. This RCT was approved by the Institutional Review Board at the University of North Texas Health Science Center (UNTHSC) in Fort Worth and funded by the Osteopathic Research Center (ORC) at UNTHSC. –Hypothesis 1: A single intervention of OMT will improve dyspnea in a stable COPD subject, as measured by response to the Borg scale with exertion, when compared to no treatment. –Hypothesis: a single intervention of OMT will improve exercise tolerance in a stable COPD subject, as measured by distance walked during the six-minute walk test, when compared to no treatment. Twenty-one subjects completed the trial, 10 in the OMT group and 11 in the no-treatment group. No significant differences were found in the Borg scale or 6MWT following OMT. This study is limited by a small sample size and single OMT intervention design; however, it does demonstrate the feasibility of this research at this institution and may lead to a larger, more definitive and funded clinical trial.Item Effects of Nitric Oxide on Right Ventricular Metabolism and Coronary Blood Flow(2000-01-09) Setty, Srinath; H. Fred Downey; Patricia A. Gwirtz; James L. CaffreySetty, Srinath Varadaraj. Effects of Nitric Oxide on Right Ventricular Metabolism and Coronary Blood Flow Doctor of Philosophy (Biomedical Sciences), January, 9, 2001, 123 pp, 3 tables, 16 figures, references, 211 titles. Nitric oxide (NO) formed from L-arginine and released from vascular endothelium causes relaxation of vascular smooth muscle via a cGMP mechanism. However, the of NO as a regulator of coronary blood flow control is unclear. NO has been shown also to reduce oxygen consumption in various in-vitro preparations, but its effect on myocardial oxygen consumption (MVO2) in the left ventricle of the working heart is controversial. The effect of NO on MVO2 in the right ventricle (RV) is unknown. This investigation delineated the effects of NO on RV MVO2 during controlled systemic and coronary hemodynamic conditions. In open chest dogs, NO synthesis was blocked by intracoronary infusion of NO synthesis with Nω-nitro-L-arginine methyl ester (L-NAME, 150 μg/min). To avoid effects of NO synthesis blockade on right coronary blood flow (RCBF), which might have altered RV MVO2, experiments were conducted during adenosine-induced maximal right coronary vasodilation (n=12). RCBF, RV MVO2, and other variables were measured at baseline and at elevated right coronary perfusion pressures (RCP). Under these conditions, L-NAME significantly increased RV MVO2 at baseline and at elevated RCP (P [less than] 0.05 vs. untreated control condition). These results indicate that NO acts to retard RV oxidative metabolism. We further characterized the role of NO on RV MVO2 during increases in RV workload, estimated as a product of heart rate X RV peak systolic pressure X RV dP/dt. RV workload, RCBF, and RV MVO2 were increased by intracoronary norepinephrine infusions at baseline RCP (n=5). L-NAME significantly reduced RCBF (P [less than] 0.05 vs. untreated control condition), and RV MVO2 was significantly higher at any measured RV workload during L-NAME (P [less than] 0.05 vs. untreated control condition). These findings indicate that NO is an important component of RCBF control and that NO blunts norepinephrine-induced increase in RV MVO2. If NO reduced RV MVO2 it may be cardioprotective during moderate right coronary hypoperfusion. Thus, we sought to determine if in fact the RV MVO2 was reduced by NO during moderate right coronary hypoperfusion (n=9). RCP was reduced to 60 (n=5) and 40 mmHg (n=4), and RCBF and RV MVO2 fell as RCP was reduced. L-NAME significantly increased RV MVO2 at RCP of 60 and 40 mmHg (P [less than] 0.05 vs. untreated control condition), although RV workload was not altered. Since NO reduced RV MVO2 without compromising RV mechanical performance, RV oxygen utilization efficiency was enhanced. Taken together, these findings demonstrate that NO has a significant dampening effect on RV MVO2.Item Endurox R4® & Gatorade®: Effects of Recovery Drinks After Prolonged Glycogen-Depleting Exercise(1999-06-01) Williams, Michael Brandon; Raven, Peter B.; Smith, Michael; Shi, XiangrongWilliams, Michael B., Endurox R4® & Gatorade®: Effects of Recovery Drinks After Prolonged Glycogen-Depletion Exercise. Master of Science (Biomedical Sciences, Integrative Physiology), June, 1999, 73 pp., 2 tables, 18 figures, references. Purpose: Eight high-fit (bicycle Vo2max=62.4 ± 1.10 ml·kg-1·min-1) male cyclists, aged 28.4±1.65 yrs, performed a two-hour endurance bicycle exercise to achieve depletion of skeletal muscle and liver glycogen. During recovery, Endurox R4 Recovery Drink®, or Gatorade®, was ingested to investigate their relative restorative capacities to enable further exercise. Methods: Each subject performed two days of testing: one for each drink presented in random order. On each testing day, the twelve-hour fasted subject performed a two-hour cycling exercise bout at 75% VO2max followed by one to three five-minute sprints at 85% VO2max. At the end of the exercise blood glucose concentrations were 3.98±0.138 mmol/L. A four hour recovery period ensued in which the subject was given 24-ounces of the recovery drink. A performance test at 85% VO2max to exhaustion was then conducted. Ventilatory responses were collected breath-to-breath, while venous blood samples were measured for oxidation products, glucose and insulin concentrations. Results: The recovery phase showed significant increases in both plasma glucose and serum insulin following Endurox R4 Recovery Drink® ingestion as compared to Gatorade®. There was a significant increase in time to exhaustion (+55%) following Endurox R4 Recovery Drink® during the performance ride compared to Gatorade®. Final oxidation products following Endurox R4 Recovery Drink® ingestion were significantly decreased as compared to Gatorade® ingestion, in that Thiobarbituric Acid Reactive Substrates (T-BARS) were significantly decreased. Conclusions: These data indicate that the Endurox R4 Recovery Drink®, when compared to Gatorade®, significantly enhanced recovery from glycogen-depleting exercise. In addition, Endurox R4 Recovery® Drink decreased the formation of final oxidation products, when compared to Gatorade®.Item Firefighter Medical Surveillance/Duty Fitness Evaluation of Content and Reporting Format: Compliance with Federal and Other Recognized Standards(2003-05-01) Lin, Rick H.Lin, Rick H, Firefighter Medical Surveillance/Duty Fitness Evaluation of Content and Reporting Format: Compliance with Federal and Other Recognized Standards. Master of Public Health (DO/MPH Dual Degree Track), May, 2001, 41 pp., 7 tables, bibliography, 11 titles. The University of North Texas Health Science Center analyzed data collected by the Public Health Preventive Medicine (PHPM) Clinic at the University of North Texas Health Science Center (UNTHSC) in the course of medical surveillance and duty fitness exams for the City of Rowlett, Texas, HAZMAT Team. Data was analyzed for content and reporting format to determine compliance with federal and other recognized standards. An aggregate report of continuous and categorical data was also created. The subjects were all firefighters in the City of Rowlett Fire Department, Rowlett, Texas. The data was collected from the results of physical exams performed on the members of this population between the period of 1-1-1996 and 12-31-1996. There were a total of sixteen subjects. (n=16) These firefighters are all HAZMAT Team members. The overall content of the medical surveillance and duty fitness examinations was evaluated. The compliance in content of medical history and physical examination to the recognized standards established by OSHA, EPA, and NFPA was examined. The physical characteristics and health of this population of firefighters is described based on the data collected. The result of the comparison shows that the UNTHSC PHPM Clinic’s forms for the history and medical exams did not completely incorporate the recognized standards. The content of the medical surveillance and duty fitness exams was in compliance with and often exceeded recognized standards.Item Hypoxic Conditioning Suppresses Cytotoxic Nitric Oxide Production Upon Myocardial Reperfusion(2007-05-01) Ryou, Myoung-Gwi; H. Fred Downey; Rong Ma; Raghu KrishnamoortyRyou, Myoung-gwi. Hypoxia conditioning suppresses nitric oxide production upon myocardial reperfusion. Master of Science (Integrative Physiology), May 2007, 61pp, 2 tables, 9 figures. This study was conducted in mongrel dogs to test the hypothesis that 20 d normobaric intermittent hypoxic conditioning (IHC) evokes cardioprotective adaptations of the myocardial nitric oxide synthase (NOS) system. Specifically, the proposal that IHC suppresses myocardial NOS activity sufficiently to dampen the cytotoxic burst of NO formation upon reperfusion of ischemic myocardium was tested. Mongrel dogs were conditioned by a 20 d program of IHC (FIO2 9.5-10%; 5-10 min hypoxia/cycle, 5-8 cycles/d with intervening 4 min normoxia). On day 21, ventricular myocardium was sampled for measuring NOS activity (colorimetric assay) and endothelial NOS (eNOS) content (immunoblot). In separate experiments, myocardial nitrite (NO2) release, an stable product of NO oxidation, was measured at baseline and during reperfusion following 1 h occlusion of the left anterior descending coronary artery (LAD). Values in IHC dogs were compared with respective values in non-conditioned, control dogs. IHC lowered left and right ventricular NOS activity by 60%, from 100-115 to 40-45 mU/g protein (P [less than] 0.01), and decreased eNOS content by 30%. IHC dampened cumulative NO2 release during the first 5 min reperfusion from 32 ± 7 to 14 ± 2 μmol/g (P [less than] 0.05), but did not alter hyperemic LAD flow (15 ± 2 vs. 13 ± 2 ml/g). Attenuation of the NOS/NO system may contribute to IHC-induced protection of myocardium from ischemia-reperfusion injury.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 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 Myocardial Blood Flow and Function During Exercise in Dogs(1995-06-01) Kim, Song-Jung; Patricia A. Gwirtz; Peter B. Raven; James L. CaffreyIntroduction. Background. Coronary circulation during exercise. Coronary blood flow is regulated primarily by local metabolic mechanisms according to the oxygen and nutrient needs of the heart (2, 4, 19). The local “metabolic signal” involves vasoactive metabolites, such as adenosine, released from myocytes in direct proportion to myocardial work (Figure 1). However, other external factors are superimposed on local regulatory mechanisms and can substantially modulate coronary blood flow. One of these modulatory factors is the sympathetic nervous system. Sympathetic vasoconstriction mediated by α-adrenergic receptors in the coronary circulation has been shown to oppose metabolic vasodilation and limit oxygen supply to the myocardium during physiologic and pathophysiological cardiac stresses, such as exercise and myocardial hypoperfusion (1, 6, 7, 8, 10-14, 17, 18, 21). This limitation on myocardial oxygenation appears to impose a restriction on the increase in regional left ventricular subendocardial contractile function during submaximal exercise (7). In this regard, studies have shown that removing this α1-constrictor tone leads to an increase in coronary blood flow and, as a result, regional contractile function (8). This adrenergic coronary constriction during exercise is mediated by neutrally released norepinephrine, not by circulating catecholamines (8). Endothelial-mediated control of coronary vascular tone. Recent investigations indicate that another factor involved in modulating coronary blood flow is the vascular endothelium. The endothelium exerts an influence on vascular smooth muscle vasomotor tone by releasing an endothelium-derived relaxing factor (EDRF) or nitric oxide (NO), which is derived from the amino acid L-arginine by nitric oxide synthase (5, 22). Synthesized NO diffuses into the underlying vascular smooth muscle to activate cytosolic guanylate cyclase (GC), thereby stimulating the intracellular accumulation of cyclic GMP (cGMP). This is illustrated in Figure 2. NO is released by the stimulation of muscarinic receptors on endothelial cells by acetylcholine, as well as by other agonists or physical stimuli (e.g., shear stress) at the interface between blood and endothelial cell surface (15). During exercise, for example, the work output of the normal heart may increase several-fold by the stimulation of sympathetic nerves to heart. The increased work output of the heart increases myocardial oxygen demand. Consequently, the coronary circulation undergoes vasodilation due to local metabolic mechanisms. The elevation in shear stress caused by increases in coronary blood flow triggers release of NO from the endothelium because of the extremely pulsatile nature of the flow. Therefore, it is likely that during exercise, release of NO by shear stress and by neurohormonal stimuli, concomitant with local release of metabolites, contributes to coronary dilation. These vasodilatory influences counteract a sympathetic α-adrenergic coronary constriction, which limits the increase in coronary blood flow and cardiac performance. Accordingly, coronary vascular smooth muscle tone during exercise is modulated by the endothelium, which responds to the increased shear stress and adrenergic stimulation, which provides the major extrinsic input.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 Effect of Exercise Training on Behavior and Oxidative Stress in Aging Mice(2005-08-01) Taylor, Sara A.; Michael Forster; Joan F. Carroll; Susan FranksTaylor, Sara A., The effect of exercise training on behavior and oxidative stress in aging mice. Doctor of Philosophy (Biomedical Sciences), August 2005, 136 pp., 17 figures, bibliography, 97 titles. Purpose: Accrued oxidative damage to brain tissue is a proposed mechanism of cognitive deficits observed in aging. In mammalian tissue, it is hypothesized that a balance normally exists between pro-oxidants (reactive oxygen/nitrogen species) and endogenous antioxidant enzymes that are able to inhibit the activity of reactive oxygen/nitrogen species. As long as this balance is maintained, oxidative damage is moderated, but if the production of pro-oxidants becomes excessive or if the activity of antioxidants lags, oxidative stress and ultimately oxidative damage to tissues may result. It is the hypothesis of this project that exercise training is able to prevent decreased antioxidant activity in brain tissue, produce a favorable shift in the pro-oxidant/antioxidant balance, and thus moderate oxidative damage in the aging mice brain. Methods: 3 and 20 month old C57BL/6 mice were either subjected to 8 weeks of treadmill exercise followed by 3 weeks of concurrent exercise and behavior testing, or else they were age-matched, non-exercised controls. Mice were tested on multiple behavioral tasks that tested sensorimotor learning as well as tasks that required utilization of various component of cognitive learning. After exercise and behavior testing regimens were completed, biochemistry assays for protein oxidative damage as well as for antioxidant enzyme activity were performed on several brain regions. Results: It is a finding of the study that moderate, short-term exercise initiated in aged C57BL/6 mice resulted in increased fitness in the aged mice to the same degree as observed in young mice, improved some psychomotor skills, including bridge-walking and reaction time, and improved age-impaired spatial memory performance. Moreover, exercise training showed a lack of effect on oxidative damage in all brain regions, increased activity of glutathione peroxidase in the cerebellum and striatum of young, but not aged mice, and it increased the activity of catalase in the cortex of aged mice. Conclusions: The data presented in this project shows that exercise does moderate some age associated cognitive deficits, and the findings do not preclude the possibility that exercise produces this effect by reducing accrued oxidative damage that occurs with aging.Item The Effect of Fitness on Cardiac Work with and without Metoprolol(2008-07-01) Hawkins, Megan Nicole; Peter Raven; Michael Smith; Robert MalletHawkins, Megan Nicole, The Effect of Fitness on Cardiac Work with and without Metoprolol. Doctor of Philosophy (Biomedical Science), July 2008; 128 pp; 3 tables; 17 figures; bibliography. Chronic endurance exercise adaptations of the cardiovascular and skeletal muscle systems. The mechanisms by which these adaptations occur, and their effect on the physiological response to exercise, have not been fully elucated. In addition, the classic concept of the role of maximal oxygen consumption (Vo2max) as a parametric index of cardiorespiratory capacity has been questioned. Therefore the purpose of the investigations presented within this dissertation was to: i)retrospectively analyze 156 incremental exercise stress tests and supramaximal exercise tests to verify that VO2 does indeed attain a maximal value; ii)evaluate the effects of cardioselective beta-adrenergic blockade on the ability to maintain cardiac work in average trained and endurance exercise trained subjects during moderate (45% VO2max) and heavy (70% Vo2max) intensity cycling exercise; and iii) determine the effect of aerobic fitness on resting and peak leg vascular conductance and the change in central blood volume observed during the onset of cycling exercise. In the first investigation we demonstrated that highly trained runners capable of maintaining supramaximal workloads achieved a VO2 that rarely exceeded the VO2max value obtained during an incremental exercise stress test. In the second investigation we demonstrated that acute β1-adrenergic receptor (βAR) inhibition reduced cardiac output, cardiac work and cardiac efficiency in endurance trained athletes during moderate and heavy intensity exercise. However, in average trained individuals these same variables were not affected during moderate exercise intensity, but were reduced at heavy intensity exercise. We concluded that βAR blockade impaired the more efficient Frank-Starling mechanism in endurance trained athletes but remained functional in average trained subjects during moderate exercise intensities. In the third investigation we demonstrated that endurance athletes responded to the onset of exercise with a larger increase in central blood volume than average trained individuals. In addition, resting and post-ischemic leg blood glow and leg vascular conductance were greater in the exercise training-induced adaptations of the skeletal muscle vasculature resulted in larger conductance capacity of the working muscle in response to increases in oxygen demand and enabled a greater increase in muscle blood flow from rest to exercise.Item Ventilatory and Heart Rate Responses to Incremental Exercise With and Without Venous Occlusion(2003-07-01) Godoy, Selena Janette; Raven, Peter B.; Forster, Michael; Shi, XiangrongGodoy, Selena J., Master of Science, Biomedical Sciences, July 2003. Ventilatory and Heart Rate Responses to Incremental Exercise With and Without Venous Occlusion. 26 pp., 4 tables, 7 figures, 29 references. We sought to identify whether the accumulation of metabolites in exercising muscle was associated with the ventilator (VT) and heart rate thresholds (HRT). Subjects performed two incremental workload cycling exercise tests to maximal effort: 1) without intervention (CON) and 2) with leg venous occlusion cuffs inflated to 90 mmHg (CUF). Breath-by-breath measures of ventilation, expired respiratory gases and beat-to-beat heart rate were collected. VT and HRT were identified using mathematical techniques for detection of thresholds. The VO2 of the VT and HRT were not significantly different at p [less than] 0.05 and were strongly correlated in both CON (r=0.84) and CUF (r=0.83). These data suggest that the accumulation of intramuscular metabolites provides a stimulus to increase ventilation and heart rate.Item Wearing a Football Helmet Exacerbates Thermal Load During Exercise in Thermoneutral and Hyperthermic Exercise(2004-12-01) Brothers, Robert Matthew; Smith, Michael; Raven, Peter B.; Shi, XiangrongBrothers, Robert Matthew, Wearing a Football Helmet Exacerbates Thermal Load During Exercise in Thermoneutral and Hyperthermic Conditions. Masters of Science (Integrative Physiology), December, 2004, 42 pp., 1 table, 4 illustrations, 55 titles in References. This investigation tested the hypothesis that wearing a football helmet during intense exercise leads to a significant increase in core temperature as indicated by esophageal temperature (Tes), head skin temperature (Th) and heart rate (HR) when compared to a similar bout of exercise performed while no helmet was worn. It was found that in both the helmet and no helmet exercise protocol there was a significant increase in the above variables when compared to baseline. The helmet condition, however, resulted in a significantly greater increase in these variables when compared to the no helmet condition. Furthermore, this effect of the helmet was further increased in a hyperthermic environment when compared to the thermoneutral environment.