Browsing by Subject "Circulatory and Respiratory Physiology"
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Item A Meta-Analysis of the Effects of Chromium on Fasting Blood Glucose, HBA1c, Triglycerdies, LDL-C and HDL-C in Type 2 Diabetes and Impaired Glucose Tolerance(2002-05-01) Evans, Jill E.; Urrutia-Rojas, Ximena; Mains, Doug A.Evans, Jill E., A meta-analysis of the Effects of Chromium on Fasting Blood Glucose, HbA1c triglycerides, LDL-C, and HDL-C in Type 2 Diabetes and Impaired Glucose Tolerance. Master of Public Health, May, 2002, 35 pp., 4 tables, 4 figures, references cited, 23 titles. Objective: To assess the magnitude of chromium’s effect of trivalent chromium (picolinate or chloride) or yeast in type 2 diabetics or subjects with impaired glucose tolerance. Efforts were taken to combine studies with similar doses and treatment periods. Sensitivity analysis was performed. Outcomes Measured: Fasting blood glucose (FBG), HbA1c, triglycerides, high-density cholesterol (HDL-C), and low-density cholesterol (LDL-C). Effect sizes were converted to appropriate units and were reported as “effect size equivalents”. Results: The magnitude of effect of chromium on FPG and HbA1c was negative and generally increased with dosage and duration. Statistically significant effects were observed for typical doses (150-250μg/day) for both outcomes at 1.5-3 months duration, and for HbA1c at 4-6 months; and high dosage (1000 μg/day) at 1.5-3 and 4-6 months for both outcomes. For triglycerides at the typical dose, statistically significant effects (p=0.00) were observed at 1.5-3 months. There was no effect on LDL-C. HDL-C increased with increasing duration of chromium supplementation, with the exception of the 4-6 month duration. Statistically significant effects (p=0.00) were observed for typical dosage at 1.5-3 months. For the studies using yeast with GTF activity, the effect size equivalent for FPG and triglycerides was significantly lowered (p [less than] 0.001 and p=0.00 respectively). When the study using yeast with no GTF activity was included, the pooled fixed effect size equivalent was smaller, yet remained significant. HDL-C was significantly increased (p=0.00). Sensitivity analysis yielded similar results. Conclusion: Meta-analysis of chromium showed a significant reduction in FBG, HbA1C, triglycerides, and LDL-C, while increasing HDL-C in the groups studied. The best available evidence suggests that chromium has a dose and duration-dependent effect on these outcomes.Item Adenosine Receptor Blockade Increases Lactate and Purine Release But Does Not Affect Functional Recovery in Isolated Rabbit Myocardium(1995-12-01) Wang, Sheng; Downey, H. Fred; He, Miao-Xiang; Mallet, Robert T.Wang, Sheng, Adenosine Receptor Blockade Increases Lactate and Purine Release but does not Affect Functional Recovery in Isolated Rabbit Myocardium Master of Science (Biomedical Sciences), December 1995; 67 pp; 3 tables; 8 figures; bibliography, 121 titles. This study tests the hypothesis that endogenous adenosine mediates recovery of cardiac function in ischemia/reperfused rabbit hearts. Isolated isovolumic rabbit hearts perfused at constant pressure was subjected to mild ischemia (perfusion pressure 50 cm H2) or moderate ischemia (perfusion pressure 30 cm H2O) for 90 min followed by 60 min of reperfusion. In treated hearts, infusion of 100 μM 8-p-sulfophenyl theophylline (SPT) was initiated 20 min before ischemia and maintained throughout the experiment. Adenosine receptor blockade did not affect left ventricular function assessed from pressure-heart rate product (PRP). Lactate release increased to 152 ± 24% of baseline during mild ischemia and 259 ± 26% of baseline during moderate ischemia in untreated hearts. Lactate release was markedly elevated at baseline, ischemia and reperfusion by SPT treatment (p [less than] 0.05 compared to untreated). Purine nucleoside release was 4.1 ±0.7 nmol · min-1 · g-1 in SPT treated group and 1.8 ± 0.24 nmol · min-1 · g-1 in untreated group during moderate ischemia (P [less than] 0.05). Myocardial efficiency was significantly lower in the SPT treated hearts (240 ± 11 mmHg · g=1 · μl-1 O2) compared to untreated hearts (300 ± 22 mmHg · g-1 · μl-1 O2) during reperfusion after moderate ischemia. In conclusion, adenosine receptor blockade stimulates glycolysis in normoxic and ischemic myocardium, but does not affect post-ischemic functional recovery.Item Alterations in Beta-Adrenergic Receptor Density on Human Lymphocytes in Response to Chronic Exercise(2000-12-01) Brittain, Adam K.; Peter B. Raven; Stephen R. Grant; Michael W. MartinA number of cardiovascular adaptations have been shown to occur in healthy individuals as a result from regular, chronic exercise training. These changes include, but are not limited to, a lower resting heart rate, a lower heart rate at any given submaximal workload, an increase in stroke volume, an increase in maximal cardiac output due primarily to an increase in contractility, a decreased peripheral vascular resistance (increased peripheral vascular conductance), an overall increase in vascularity, an increase in left ventricular mass, and an increase in total body oxygen extraction (Raven, 1994). Some of these adaptations are also known to commonly occur in patients with coronary artery disease enabling them to increase their total work capacity. Therefore, exercise apparently adapts the heart to better cope with the adverse affects of coronary artery disease and helps to prevent the aforementioned disease from developing in healthy individuals. The beta-adrenergic receptor (β-AR) is essential for the activation of many aspects of the cardiovascular system during dynamic exercise (1). The catecholamines epinephrine and norepinephrine are released from the adrenal medulla and postganglionic fibers of the sympathetic nervous system respectively in response to dynamic exercise. Epinephrine and other beta-adrenergic receptor agonists bind and activate the β-AR on the cell membrane thus allowing it to couple with the stimulatory GTP-binding regulatory protein Gs. This step initiate the activation of adenylate cyclase and the synthesis of cyclic adenosine 3’,5’ monophosphate (cyclic AMP), a key intracellular second messenger. Cyclic AMP ultimately activates cyclic AMP-dependent protein kinase (PKA), an enzyme that phosphorylates a number of intracellular proteins that subsequently influence cell metabolism and function. Alterations in the activity of the adrenergic system seen in several clinical and physiological situations, including exercise, are directly associated with changes in lymphocytic β-AR density or function (2). Moreover, it has been suggested that the changes in receptor density on lymphocytes correlate closely with cardiovascular responsiveness to catecholamines in humans (3-6). Additionally, changes in catecholamine concentration within the physiological range have a regulatory effect on β-AR density and function (7). One particular study established an inverse relationship between plasma and urine catecholamine concentrations and lymphocytic β-AR density in man (8). It is the intent of this review to describe some of the cardiovascular adaptations that occur as a result of chronic exercise and how these changes could be caused by alterations in β-AR density and responsiveness. Additionally, the comparisons and contradictions between chronic heart failure and chronic exercise will be made. The role of the beta-adrenergic system in mediating the effects of exercise will be introduced. The structure of the β-AR will be described and how its molecular structure dictates its function. A brief synopsis will be presented on the mechanism in which β-AR operates subsequent to ligand binding. Alterations of the β-AR, particularly its expression in the heart, through transgenics will then be reviewed to show how this receptor could be responsive for some of the aforementioned adaptations to chronic exercise. In this, some of the differences between the β1- and β2-AR will be described as well as some of the therapeutic implications that could result from overexpression of the β-AR. Following this, alterations in the density of the β-AR after both short-term and long-term exposure to catecholamines will be examined. Included in this section with be the detailed description of the mechanism of receptor desensitization that precedes receptor down-regulation. A brief review will then be given on the effects of chronic exercise on β-AR density. The use of human lymphocytes as model cells will then be described. Binding theory will be explained as it will be the basis of methodology used in any subsequent studies. Along with this, [125 Iodo] cyanopindolol (125I-CYP) will be introduced and its advantages and disadvantages as a β-AR ligand probe will be discussed.Item Asthma Mortality and Toxic Release in Texas - An Ecological Study 1980-2001(2004-05-01) Maddipatla, Sreeram; Manuel BayonaMaddipatla, S., Asthma Mortality and Toxic Release in Texas - An Ecological Study 1980-2001. Master of Public Health (Environmental Health) April 2004, 97 pp., 4 tables, bibliography, 94 titles. There is a lack of literature examining how the spatiotemporal trend of asthma may have impacted different ethnic/racial compositions of Texans. The present study sought to evaluate the geographic-temporal variations in asthma mortality in Texans over a 22-year period, retrospectively, and examine whether the trend of environmental Toxic Release Inventory (TRI) concentrations and their spatiotemporal persistence might place an uneven burden on particular racial groups. The study concentrates on the time period between 1980-2001 and first evaluates geographic excess of asthma mortality in different racial groups at the county level and characterizes the excess burden by spatiotemporal variations. After this assessment, the impact of TRI on asthma mortality over this period of time is analyzed. Based on these two analyses, this would identify which racial/ethnic groups in which Texas regions might have been affected the most by regarding mortality over time, and suggested priority geographic areas for policy intervention. At the end of this study, it could be said that there might be an association between the TRI release and increased asthma mortality in the Black male population.Item Cardiac Autonomic Response to Hypovolemia --- Effect of Age(1997-08-01) Wang, Hong-Wei; Raven, Peter B.; Shi, Xiangrong; Caffrey, James L.Objective: The beat-to-beat variation in heart rate reflects the dynamic response of the cardiovascular control systems to physiological perturbations such as respiration and postural change. The heart rate variation (HRV) is a part of the rapidly reacting component of cardiovascular homeostasis largely influenced by parasympathetic and sympathetic input. Thus, beat-to-beat variation in heart rate can be used as a measure of cardiac autonomic responses. The standard deviation of R-R interval is a measure of the overall variability in heart rate and has been shown to decrease with aging (9,23). This measure, however, can not identify individual sources of the variation. Spectral analysis reduces a signal to its constituent frequency components and the relative power of these components has been indicated related to parasympathetic mediation, combined sympathetic and parasympathetic mediation, and sympathetic mediation (1, 14, 17). Limited data are available regarding power spectral analysis of heart rate variation to study aging changes under orthostatic stress. An attenuated cardiac sympathetic nerve activity was found in older group vs younger individuals (7, 11, 19) during posture change. However, these studies were carried out using either posture change from to upright or passive head-up tilt. During these posture changes, both cardiopulmonary baroreceptors (i.e., intrathoracic hypovolemia) and arterial baroreceptors (postural hypotension) were unloaded. Therefore, it is unclear whether there is any difference in the HR variability between the young and the elderly during unloading of cardiopulmonary baroreceptors (or low-pressure baroreceptors) alone. In this study, we investigated the age difference in cardiac autonomic modulation of heart rate during unloading of cardiopulmonary baroreceptors with or without systemic arterial hypotension. For the purpose, we examined beat-to-beat heart rate variability in both the time and frequency domain using power spectral analyses in healthy individuals from ages 18 to 68 under basal conditions and in response to graded lower body negative pressure induced central hypovolemia. Not only individual low and high frequency spectral content were analyzed and those parameters were compared in order to find a quantitative evaluation of sympathetic and parasympathetic modulation and under the graded lower body negative pressure.Item Cardiac Parasympathetic Dysfunction in Morphine Addiction(1997-12-01) Napier, Leslie D.; Caffrey, James L.; Raven, Peter B.; Gwirtz, Patricia A.Napier, Leslie D., Cardiac Parasympathetic Dysfunction in Morphine Addiction. Doctor of Philosophy (Biomedical Sciences), December, 1997, 137 pp., 9 tables, 22 figures, references, 163 titles. The effects of chronic morphine treatment on parasympathetic control of the heart and associated cellular mechanisms were examined using a canine model. Vagal bradycardia was significantly blunted in dogs treated for one week with subcutaneous morphine pellets. In a separate group of dogs, heart rate and high frequency fluctuations in heart rate declined during the first three hours of subcutaneous morphine infusion consistent with the vagatonic action of acute morphine. Heart rate remained below baseline on Day 2 of the morphine infusion but had returned to normal by Day 10. Ambient sympathetic tone was increased on Days 2 and 10, and plasma catecholamines were elevated on Day 2. The intrinsic heart rates on Days 2 (160 bpm) and 10 (162 bpm) of morphine treatment were lower than the pre-treatment rate (182 bpm). Suggested mechanisms include a fundamental change in sinoatrial nodal cell function or attenuated tachycardia induced by vasoactive intestinal peptide co-released with acetylcholine from post-ganglionic parasympathetic neurons. The time to 50% maximal bradycardia during vagal nerve stimulation was increased with chronic and acute morphine suggesting an effect on the rate of acetylcholine synthesis, release or degradation. Muscarinic receptor density in left ventricular and right atrial sarcolemmal membranes from dogs treated chronically with morphine were 34% and 17% higher, respectively, than in control animals. Chronic morphine had no effect on basal or MnCl2-stimulated cyclase activity in either region. Similarly, maximal β-adrenergic and muscarinic receptor/G-protein coupling to adenylate cyclase were not altered by chronic morphine. Atrial norepinephrine content was higher than that in the ventricles and was unaltered by morphine. Ventricular norepinephrine was decreased with chronic but not acute morphine treatment. Epinephrine was evenly distributed throughout the myocardium and was reduced in both the atria and the ventricles by either acute or chronic morphine. This pattern suggests that morphine may reduce extraneuronal uptake of catecholamines. Collectively these studies show that chronic morphine treatment and the accompanying persistent vagal activity may reduce parasympathetic function. This attenuated function, however, is short-lived since sympathetic systems adapt with compensatory responses masking, or perhaps reversing, initial parasympathetic deficits.Item Characterization of the Serotonin Receptors in the Long Posterior Ciliary Artery of the Bovine Eye(2000-08-01) Landry, Theresa A.; Quist, Eugene; Martin, Michael; Pang, Iok-HouLandry, Theresa A., Characterization of the Serotonin Receptors in the Long Posterior Ciliary Artery of the Bovine Eye. Doctor of Philosophy (Biomedical Science), August 2000, 14 pp., 5 tables, 29 illustrations, bibliography, 104 titles. Vascular disease and vasospasm are implicated in the etiology of glaucoma. The long posterior ciliary (LPCA) is the major blood supply for the ciliary body including the ciliary processes that produce aqueous humor. Information about the pharmacological control of this vessel would be helpful in understanding its normal and pathologic function. Serotonin (5-HT) is a neurotransmitter that effectively constricts the LPCA. The objective of this research is to identify the serotonin receptor subtype responsible for the 5-HT induced vasoconstriction of the LPCA and to characterize the cellular mechanisms that mediate that contraction. Ring segments of the LPCA were dissected from bovine eyes and mounted on tungsten triangles attached to a force transducer. Changes in vascular tension were measured and recorded using a physiography recorder. Dose response curves with 5-HT, 5-HT 1-like agonist, 5-CT, and 5-HT2 agonist, α-methyl-5-HT, indicate that the 5-HT 1-like receptor contributed about 15.13% to the contraction and the 5-HT2 receptor contributed to 61.61%. The EC50 for the three agonists were 283 nM (5-HT), 336 nM (5-CT), and 1.7 μM (α-methyl-5-HT). Inhibition curves with selective antagonists indicate that the IC50 is (5-HT 1-like antagonist) and ketanserin (5-HT2 antagonist). Following incubation of the rings with diltiazem 10 μM or nifedipine 10μM, the response to 5-HT was reduced 65.*% and 61.7% respectively. Incubation in calcium free PB produced similar results. Ryanodine inhibited the 5-HT contraction by 58.1% and caffeine inhibited the response 100%. PKC inhibitors bisindolymaleimide II 1 μM, disindolylamalemide II 10 μM, chelerythrine 25 μM and H-7 5 μM decreased the 5-HT response by19.8%, 55.7%, 31.1% and 61.5% respectively. Incubation of the ring segments with one of three PLC antagonists, 2-NCDC 70 μM, U73122 0.5μM, or neomycin 5 mM, prior to the addition of 1 μM serotonin, significantly reduced the contraction of each vessel, p [less than] 0.0001. The 5-HT-induced vasoconstriction of the LPCA of the bovine eye is mediated through activation of both 5-HT2 and 5-HT 1-like receptors. The contraction is dependent on the mobilization of calcium and is mediated in part through PLC activated intracellular calcium release from IP3 sensitive stores.Item Control of the Peripheral Vasculature During Exercise: Angiotensin II(2007-04-01) Brothers, Robert Matthew; Peter B. Raven; Michael Smith; Patricia GwirtzBrothers, Robert Matthew, Control of the Peripheral Vasculature During Exercise Angiotesin II. Doctor of Philosophy (Biomedical Science), April 2007, 126 pp; 3 tables; 12 figures; bibliography. Control of the vasculature during exercise is balance between sympathetic vasoconstriction and metabolic vasodilation. There is an exercise intensity dependent reduction in vasoconstriction resulting in a shift towards vasodilation within “metabolically active” muscle and tissues, a phenomena known as “functional sympatholysis”. Previous studies investigating the alpha-receptors during exercise have used intra-arterial infusions of alpha-agonists. These studies indicate that alpha-receptor vasoconstrictionis completely attenuated during mild intensity exercise. When the alpha receptors are pharmacologically blocked the magnitude and onset of “functional sympatholysis” is not as drastic when compared to the agonist infusion studies. Intense exercise also activates the renin-angiotesin-system leading to production of angiotensin II (AngII), which increases exponentially at approximately 55% maximal oxygen uptake (55% VO2max). While the mechanisms of “functional sympatholysis” has been extensively studied less is known about the role of AngII in the control of the vasculature during exercise. Therefore, the purpose of the investigations within this dissertation was to: i)determine if alpha-1- blockade in an exercising human model will identify a greater maintenance of alpha-1 mediated vasoconstriction when compared to agonist infusion studies; ii) to determine if the metabolites produced within the active skeletal muscle will attenuate angiotensin II vasoconstriction; and iii) to determine if AngII vasoconstriction provides a greater percentage contribution to vascular tone as exercise intensity increases. We demonstrated that i) pharmacologic alpha-1-blockade identified a greater maintenance of alpha-1 vasoconstriction during moderately heavy exercise; and ii) this effect decreased as intensity increased in the exercising leg and increased with intensity in the non-exercising leg. In the second investigation we demonstrated that AngII and phenylephrine (PE) mediated vasoconstriction were attenuated to a similar degree during low and mild intensity exercise. In the third investigation we observed that AT1-receptor blockade; 1) attenuated the increases in MAP that occur during high-intensity exercise; ii) did not affect the vasculature in the exercising leg but; iii) we identified that AngII does partially control the vasculature in a “non-metabolically active” muscle group.Item COPD Handout materials(2008-01-01)Item Coronary Perfusion Pressure-Induced Changes in Coronary Vascular Volume in the Canine Right Ventricle(1997-12-01) Yu, Ying; H. Fred Downey; Robert T. Mallet; Michael L. SmithYu, Ying, Coronary Perfusion Pressure-induced Changes in Coronary Vascular Volume in the Canine Right Ventricle. Master of Science (Biomedical Sciences), December 1997; 33 pp; 4 tables; 5 figures; bibliography, 24 titles. Changes in coronary perfusion pressure cause changes in myocardial contractile function and oxygen consumption (MVO2), particularly in the right ventricle (RV). This study determined the effects of right coronary (RC) perfusion pressure (RCP) on RC vascular volume (RCB) and its relationship to MVO2 of in situ, working canine hearts, and also investigated whether changes in MVO2 are due primarily to altered RCP or RC blood flow (RCF). In 15 open chest, anesthetized dogs, the RC artery was cannulated and perfused with arterial blood diverted from a femoral artery. To blunt RCP-induced changes in RCF, vasopressin was infused into the RC perfusion line in seven dogs. RCV was measured by an indicator dilution method as RCP was varied without vasopressin (RCP=60, 100, 140, and 180 mmHg) and with vasopressin (RCP=60 and 100 mmHg). Without vasopressin, changes in RCP induced changes in MVO2 which were associated with changes in RCV and RCF. With vasopressin, increasing RCP from 60 mmHg to 100 mmHg produced no changes in RCF, RCV, or MVO2. These results indicate that RCP-induced changes in RV MVO2 are mediated by RCV and/or RCF, but not by RCP per se.Item Cross-Bridge Kinetics of Cardiac Myofibrils Carrying Myopathy-Causing Mutation(2007-05-01) Dumka, DishaDumka, Disha., Cross-bridge kinetics of cardiac myofibrils carrying myopathy-causing mutation. Doctor of Philosophy (Biochemistry and Molecular Biology), May 2007, 98 pp., 8 tables, 23 illustrations, and bibliography: 102 titles. Familial hypertrophic cardiomyopathy is a disease characterized by left ventricular hypertrophy and myofibrillar disarray. It is caused by mutations in sarcomeric proteins, including the ventricular isoform of myosin regulatory light chain (RLC). We have focused on one particular mutation of RLC-substitution of glutamic acid (E) at position 22 for lysine (K). The E22k mutation is located in the RLC Ca2+ -binding site. Earlier work has demonstrated that phosphorylation and Ca2+ binding are significantly altered by the E22K mutation. Studies with transgenic (Tg) mice have demonstrated that E22K-RLC mutation increases Ca2+ sensitivity of myofibrillar ATPase activity and steady-state force. However, the mechanisms for the E22K-mutated myocardium that could potentially trigger hypertrophy as seen in human patients harboring this mutation remain unclear. In order to better understand the impact of the E22K-RLC mutation on cardiac muscle contraction, we have studied the three primary parameters which best reflect the mechanism of actomyosin cross-bridge cycling during force generation. Tau one and two (t1 and t2) are the mechanical parameters which measure the dissociation and rebinding time of myosin heads from actin, respectively. Tau three (t3) is an enzymatic parameter which measures the dissociation time of ADP from the active site of myosin. For this study single-turnover contraction experiments were performed on Tg (wild-type and E22K) and non-Tg mouse cardiac myofibrils. Tau one (t1) was statistically greater in Tg-m (Tg-E22K) than in controls indicating that the E22K mutation slows down the rate of cross-bridge dissociation. However, the in-vitro binding experiments showed no difference in binding properties of T g-m vs. Tg-wt myosin to fluorescently labeled actin suggesting that this was a function of genetic manipulation rather than an intrinsic change to muscle. The slight increase in t1 was probably cause by myofibrillar disarray. Tau two (t2) was shorter in Tg-m than in non-Tg, but the same as in Tg-wt indicating that the decrease in Tg hearts was probably caused by replacement of the mouse RLC for the human isoform in the transgenic mice. Tau three (t3) was the same in Tg-m and in controls indicating that the E22K mutation had no effect time of ADP dissociation from the myosin active site. Thus the E22K mutation did not affect the three parameters that were used to study the cross-bridge kinetics of the cardiac muscle from the transgenic mice carrying the E22K-RLC mutation. On extrapolating the results of this study with transgenic mice to humans, it is likely that the change in cross-bridge kinetics is not the primary trigger through which E22K-RLC mutation affects muscle contraction. However one possible limitation of this study is that the Tg-E22K mice did not completely recapitulate the human phenotype of E22K-mutation. Overall, in this study, we successfully followed the mechanical and the enzymatic events in a small population of cross-bridges (~400) in contracting Tg-m cardiac myofibrils. The characterization of motion of a small population of cross-bridges is important because the different steps of cross-bridge cycle do not become obscured and thus it becomes easy to detect any changes in the cross-bridge cycle.Item Effects of Cervical Manipulation on Cardiac Autonomic Control(2006-05-01) Giles, Paul David; Michael Smith; Scott Stoll; Walter WitryolGiles, Paul David, Effects of Cervical Manipulation on Cardiac Autonomic Control. Master of Science (Clinical Research and Education – OMM), May 2006, pp, 1 table, 8 figures, references. Objective: Osteopathic Manipulative Medicine treatment (OMT) regimes often focus on treating the Autonomic Nervous System (ANS) in addition to biomechanics. Techniques focused on the upper cervical spine are theorized to affect the function of the vagus nerve and thereby influence the parasympathetic branch of the ANS. This study was conducted to observe the effect of upper cervical spine manipulation on cardiac autonomic control as measured by heart rate variability (HRV). Methods: Nineteen healthy, young adult subjects were randomly assigned an order in which they would undergo three different experimental protocols: OMT, Sham, and a time control. Six minutes of electrocardiographic data was collected before and after each intervention to be analyzed by power spectral analysis. Results: All baseline data for each protocol and all parameters studied were the same. The OMT protocol and all parameters studied were the same. The OMT protocol caused a change in the standard deviation of the normal-to-normal (SDNN) intervals (0.121 +/- 0.0822 sec, p=0.005) and the change in the high frequency HRV was different from the changes caused by other interventions (p=0.038). Conclusions: This preliminary data supports the hypothesis that under cervical spine manipulation affects the parasympathetic nervous system; however, more data on more subjects needs to be collected in order to clarify some points, and to reach statistical significance in certain measures.Item Effects of Compression of the Fourth Ventricle on Sleep Latency(2003-05-01) Holland, Bradly Shane; Michael Smith; Russel Gamber; Scott StrollHolland, Bradly Shane, Effects of Compression of the Fourth Ventricle on Sleep Latency. Master of Science (Clinical Education and Research), May 2003, pp, 2 tables, 3 figures, references. Hypothesis: Compression of the fourth ventricle decreases sleep latency independent of therapeutic touch. Methods: Subjects participated in CV-4 treatment, sham treatment, and control. Order was randomized. Electrocardiogram and electroencephalogram tracings, heart rate, and blood pressure were recorded. After the treatments, data were collected for 30 minutes. Data were collected during the control for 30 minutes. After the first two treatments, subjects had a one hour recovery period. Results: The ANOVA showed a difference between groups (F=28.462, power=.998, p [less than] .001). Pairwise comparison showed sleep latency was shorter for CV-4 than sham or control. There was no difference between sham and control. For total percent sleep, an ANOVA showed a difference between groups (F=20.5, power=.982, p=.001). Pairwise comparison revealed differences between control and CV-4, control and sham, but not CV-4 and sham. Conclusions: CV-4 shortens sleep latency independent of light touch.Item Effects of Endurance Training on Aortic and Carotid Baroreflex Function(1999-06-01) Smith, Scott Alan; Peter B. Raven; Michael Smith; Patricia A. GwirtzSmith, Scott Alan, Effects of Endurance Training on Aortic and Carotid Baroreflex Function. Doctor of Philosophy (Biomedical Sciences), June 1999; 122 pp; 8 tables; 10 figures; bibliography, 148 titles. Arterial bareflex control of cardiac function is dependent upon afferent input from both the aortic arch and carotid sinus bareceptors. Extensive research in animals has generated conflicting results as to the range of arterial pressures over which each baroreflex operates. Further, the complex integration of afferent signals within the medullary cardiovascular center, in reference to aortic and carotid baroreceptor input, has been characterized as additive, inhibitory, and facilitatory in nature. Such reports make it difficult to draw definitive conclusions about the behavior or central neural processing within the brainstem. In addition, these relationships have yet to be examined in humans. Therefore, the purpose of the investigations described herein, was to quantify the range of pressures over which the arterial aortic and carotid baroreflexes operate as well as to describe the interactive relationship between the aortic and carotid baroreceptors. In order to investigate these questions, we isolated the arterial, aortic, and carotid-cardiac baroreflexes in volunteer subjects generating sigmoidal stimulus-response curves for each reflex arc. Arterial and aortic baroreflex (ABR) control of heart rate (HR) was assessed by inducing graded increases and decreases in mean arterial pressure (MAP) by bolus infusion of the vasoactive agents phenylephrine (PE) and sodium nitroprusside (SN), respectively. Carotid baroreflex (CBR) function was determined utilizing ramped five second pulses of both pressure and suction applied to the carotid sinus via a neck chamber collar, independent of drug administration. The MAP at which the threshold and saturation were elicited did not differ among the reflexes examined indicating each reflex operated over a similar range of arterial pressures. Further, the simple sum of the independently driven HR response ranges of the CBR and ABR was significantly greater than that produced when both baroreceptor populations were concomitantly stimulated (i.e. arterial baroreflex) suggesting an inhibitory interaction. To investigate differential baroreflex control of HR in response to chronic endurance exercise training, a second investigation was designed implementing the reflex isolation techniques described previously. Stimulus-response relationships were compared between high fit (maximal oxygen uptake, VO2max [greater than] 60ml˖kg-1˖min-1) and average fit (VO2maxml˖kg-1˖min-1) individuals. Interestingly, neither the range of operating pressures for each reflex nor the integrative relationship between the ABR and CBR were altered as a result of aerobic training. However, the HR response range elicited from the aortic baroreceptors as a result of hypotensive and hypertensive insult was markedly attenuated in the aerobically trained population compared to their sedentary counterparts, exclusively causing a requisite reduction in arterial baroreflex sensitivity.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 Elimination of Post-Exercise Hypotension Impairs Plasma Volume Recovery(1996-12-01) Hayes, Patrick M.; Peter B. RavenHayes, Patrick M., Elimination of Post-Exercise Hypotension Impairs Plasma Volume Recovery. Master of Science (Biomedical Sciences), December, 1996, 18 pp., 2 tables, 5 figures, bibliography, 20 titles. The aim of this study was to test the hypothesis that plasma volume (PV) recovery following exercise was facilitated by post-exercise hypotension. Seven volunteers performed 2 bouts of cycling exercise for 60 minutes followed by 90 minutes of seated recovery without intervention (trial 1) or with phenylephrine infusion (PE) started at 10 minutes of recovery (trial 2). Blood samples were taken throughout the protocol at specific times, and were analyzed to measure hematocrit (Hct), hemoglobin (Hb), protein content and electrolyte levels. Plasma volume was measured using the Evans Blue Dye dilution technique and estimates of changes from resting values were then calculated from Hct and Hb values. While PV approached baseline levels at 30 minutes into recovery in trial 1, the change in PV remained significantly below control values with PE. We concluded that the diminished gain in the change in total proteins (significant increase without PE, no difference from control with PE) contributed to the impaired recovery of PV observed in trial 2, and that this difference in protein shift is attributable to the elimination of post-exercise hypotension.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 Functional Heterogeneity in Canine Coronary Resistance Arteries(1994-06-01) Parker, James Bruce; Peter B. Raven; Patricia A. Gwirtz; James CaffreyParker, James B., Functional Heterogeneity in Canine Coronary Resistance Arteries. Doctor of Philosophy (Biomedical Sciences), June, 1994, 89 pages, 21 illustrations, bibliography, 82 titles. Two thirds of the coronary vascular resistance resides in the smallest arteries and investigators have hypothesized that they may respond differently to endogenous vasoactive substances. The arterial responses to norepinephrine, acetylcholine, and adenosine were evaluated in large ([greater than] 700 μm, n=24), intermediate (400 600 μm, n=24), and small arteries (μm, n=24). Maximal vessel lumen diameter (Dmax) was determined in CA++ free medium. A reference diameter (84 ± 4.3% of Dmax) was established by re-equilibration in medium containing 2.0 mM Ca++. Arterial maximal responses as a percentage of Dmax to norepinephrine, acetylcholine, and adenosine are given in table 1: Table 1; Large % of Dmax; Inter. % of Dmax; Small % of Dmax; Norepinephrine; 41 ± 2.3; 50 ± 4.2; 83 ± 2.4; Acetylcholine; 96 ± 2.7; 88 ± 3.9; 78 ± 1.9; Adenosine; 71 ± 1.8; 81 ± 4.2; 96 ± 1.4. The sensitivity of canine coronary arteries to norepinephrine, acetylcholine, and adenosine in terms of ED50’s are given in table 2: Table 2; Agonists; Large ED50 μM; Inter. ED50 μM; Small ED50 μM; Norepinephrine; 0.037 ± 0.002; 0.078 ± 0.004; no response; acetylcholine; 0.028 ± 0.003; 0.087 ± 0.005; 0.309 ± 0.03; Adenosine; 0.295 ± 0.002; 0.095 ± 0.004; 0.035 ± 0.03. These data indicate that canine arterial responses to the native agonists norepinephrine, acetylcholine, and adenosine are heterogeneous and that neural control predominates in the larger “transport” arteries while local control predominates in the smaller “distributive” arteries. Responses of small and intermediate isolated canine coronary arteries (lumen diameter 147±42μm, and 531±37μm respectively) to norepinephrine were evaluated after pharmacological or mechanical interruption of endothelial relaxing activity. Following with the nitric oxide synthase inhibitor N-Nitro-L-Arginine Methylester (L-NAME) 10^-5 M the small and intermediate vessels spontaneously constricted to 73±4.1% of Dmax indicating a significant basal release of nitric oxide. After L-NAME or endothelial disruption graded additions of norepinephrine now reduced the vessel diameter in previously unresponsive small arteries. These data suggest that the weak and equivocal response of coronary resistance arteries to norepinephrine results from the competitive dilatory influence of endothelial derived nitric oxide production and not to the absence of norepinephrine receptors.Item Hemorrhagic Hypotension Alters Circulating and Myocardial Enkephalins and Catecholamines(1994-11-01) Mateo, Zaira; Caffrey, James; Napier, Leslie; Yoshishige, DariceMateo, Zaira, Hemorrhagic hypotension alters circulating and myocardial enkephalins and catecholamines. Master of Science (Biomedical Sciences). November, 1994. A variety of plasma and intrinsic cardiac enkephalins were extracted, chromatographed and assayed under control conditions and during two hours of hemorrhagic hypotension. The animals were anesthetized, instrumented and sufficient blood was withdrawn as required to reduce mean arterial pressure and maintain it at 40 mmHg. Central venous blood samples were obtained 15 minutes before and at 30 minute intervals during the experiment. Arterial blood gases remained stable throughout the experiment while pH declined from above 7.4 to near 7.1. Heart rate rose gradually by 100 bpm. Plasma catcholamines were unchanged during two hour time-controls. Plasma norepinephrine and epinephrine increased by 6 and 100 fold respectively, during the first hour of hypotension and remained high through the second hour. All eight enkephalin immunoreactivities monitored were unchanged during the time-controls. Plasma met-enkephalin (ME) and Peptide-F both gradually increased by 70-100% during the hypotension. Plasma Met-enkephalin-Arg-Phe (MEAP) and Peptide-B concentrations increased 4-5 fold during the same interval. Proenkephalin and other large enkephalin containing peptids though present, were unchanged during hypotension. Myocardial norepinephrine was preferentially concentrated about 3:1 in the atria. Both atrial and ventricular concentrations were reduced by one third or more following two hours of hypotension. Proenkephalin and peptide-B accounted for 75% of the intrinsic enkephalins and their ventricular concentrations were 3 to 4 times atrial concentrations in the same hearts. Intrinsic cardiac MEAP concentrations were 15-25 times higher than comparable ME concentrations in the same myocardial regions. Hypotension produced a significant increase in Peptide-B and proenkephalin compared to controls. The increase was consistent throughout the heart, thus maintaining the preferential concentration in the ventricles. Myocardial ME, MEAP and Peptide-F were largely unchanged in hypotensives compared to time-controls. The data demonstrate the preferential processing and retention of MEAP rather than ME-immunoreactive enkephalins in heart tissue. The data also indicate the responsiveness of MEAP-ir to changes in the circulatory environment and their subsequent appearance in plasma during hemorrhagic hypotension. Prior data suggests that intrinsic cardiac enkephalins may actively regulate either vagal control of the heart or sympathetic control of vasomotor tone.Item Horse Serum High Density Lipoproteins as Drug Transporters(2004-05-01) Johnson, Shemedia; Walter McConathyJohnson, Shemedia J., Horse Serum High Density Lipoproteins (HDL) as Drug Transporters. High-density lipoproteins (HDL) are complex particles composed of specific proteins and lipids that facilitate blood and tissue cholesterol homeostasis by transporting excess peripheral cholesterol to the liver. In association with cholesterol ester transfer protein (CETP) and the enzyme, lecithin: cholesterol acyltransferase (LCAT), HDL contributes to the transport of hydrophobic lipids, including cholesterol ester and triglycerides through the blood. The studies presented here involve the evaluation of horse serum HDL as a carrier of water insoluble drugs and an improved process to isolate and purify horse serum HDL utilizing hydrophobic affinity chromatography. Dilauryl fluorescein (DLF) has been chosen as a model compound for the study of horse HDL as a drug carrier. The prepared HDL/DLF particles have similar flotation densities and size properties to native horse serum HDL. The amount of DLF incorporated into HDL is 30μg/mg protein. Various cancer cell lines internalized DLF from horse HDL/DLF particles successfully. While human plasma contains cholesterol ester transfer protein (CETP), horse plasma does not. Horse plasma/serum can be supplemented by human plasma to study the role of CETP in drug transport and the stability of the horse HDL/drug complex.
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