ABSTRACT Purpose: The primary aim of the study (i.e. Chapter 3) was to compare the magnitude of retinal vascular reactivity in arterioles of varying diameter in healthy, young subjects. The secondary aims were to determine: a) if there are any order effects in terms of provoking vasoconstriction or vasodilation first; and b) the repeatability of the vascular reactivity measurements. An additional aim (i.e. Chapter 4) was to determine the effect of healthy aging on the relationship between retinal vascular reactivity and vessel diameter. Method: The sample comprised 10 healthy, young subjects (mean age 26.5 years, SD 4.04) and 7 healthy, older subjects (mean age 55.43 years, SD 5.41). Each subject from the young age group attended for three sessions. The first session was used to determine eligibility and select hemodynamic measurement sites. At sessions 2 and 3, O2 and CO2 were sequentially administered to the subjects using a face mask and sequential re-breathing circuit (to maintain standardized hyperoxia and hypercapnia). The order of vasoconstriction and vasodilation was varied across sessions 2 and 3. The design of the protocol was simplified for the subjects from the older age group. Each subject from the older group attended for one visit. O2 and CO2 were administered to the subjects using a face mask and sequential re-breathing circuit. The order of gas provocation was varied among the subjects (i.e. hyperoxia or hypercapnia first). For both groups, measurements of vessel diameter, centerline blood velocity and derived blood flow were acquired at each condition (i.e. baseline, during stabilized vasoconstriction, vasodilation, and recovery) at two discrete measurement sites along the supero-temporal arteriole. Results: The results of the repeated measures ANOVA showed a significant difference between the narrow and wide measurement sites for the younger group for flow (p??? 0.0003) and a significant influence of inspired gas provocation on flow for both protocols (p<0.0001). In addition, the interaction of measurement site and inspired gas provocation was significant (p<0.0001). The magnitude of retinal vascular reactivity showed a significantly greater blood flow response for the wide measurement site (p<0.0001). O2 provocation resulted in vasoconstriction that was still present up to 10 minutes after cessation of the stimulus (order effect of O2; p???0.046). No such order effect was apparent for CO2 provocation (order effect of CO2; p=0.352). The group mean blood flow Coefficient of Repeatability (COR) for the narrow measurement site was 0.74 ??l/min (relative to group mean flow of 4.85 ??l/min ?? SD 1.31) and for the wide measurement site was 1.49 ??l/min (relative to group mean flow of 11.29 ??l/min ?? SD 3.55). There was no difference between the young and the older age groups in retinal vascular reactivity for both the narrow (two-tailed Student t-test, p=0.8692) and wide (two-tailed Student t-test, p=0.2795) measurement sites. Conclusion: This study demonstrated that the magnitude of retinal vascular reactivity was greater for arteriolar measurement sites with wider baseline vessel diameters. In addition, it demonstrated that hyperoxic provocation resulted in a persistent vasoconstriction up to 10 minutes after cessation of the stimulus. The study demonstrated that the repeatability of retinal blood flow measurements in absolute terms is lower for smaller diameter vessels. Finally, this study also suggests that age does not affect the relationship between retinal vascular reactivity and vessel diameter.

No description available.

ABSTRACT Purpose: The primary aim of the study (i.e. Chapter 3) was to compare the magnitude of retinal vascular reactivity in arterioles of varying diameter in healthy, young subjects. The secondary aims were to determine: a) if there are any order effects in terms of provoking vasoconstriction or vasodilation first; and b) the repeatability of the vascular reactivity measurements. An additional aim (i.e. Chapter 4) was to determine the effect of healthy aging on the relationship between retinal vascular reactivity and vessel diameter. Method: The sample comprised 10 healthy, young subjects (mean age 26.5 years, SD 4.04) and 7 healthy, older subjects (mean age 55.43 years, SD 5.41). Each subject from the young age group attended for three sessions. The first session was used to determine eligibility and select hemodynamic measurement sites. At sessions 2 and 3, O2 and CO2 were sequentially administered to the subjects using a face mask and sequential re-breathing circuit (to maintain standardized hyperoxia and hypercapnia). The order of vasoconstriction and vasodilation was varied across sessions 2 and 3. The design of the protocol was simplified for the subjects from the older age group. Each subject from the older group attended for one visit. O2 and CO2 were administered to the subjects using a face mask and sequential re-breathing circuit. The order of gas provocation was varied among the subjects (i.e. hyperoxia or hypercapnia first). For both groups, measurements of vessel diameter, centerline blood velocity and derived blood flow were acquired at each condition (i.e. baseline, during stabilized vasoconstriction, vasodilation, and recovery) at two discrete measurement sites along the supero-temporal arteriole. Results: The results of the repeated measures ANOVA showed a significant difference between the narrow and wide measurement sites for the younger group for flow (p≤ 0.0003) and a significant influence of inspired gas provocation on flow for both protocols (p<0.0001). In addition, the interaction of measurement site and inspired gas provocation was significant (p<0.0001). The magnitude of retinal vascular reactivity showed a significantly greater blood flow response for the wide measurement site (p<0.0001). O2 provocation resulted in vasoconstriction that was still present up to 10 minutes after cessation of the stimulus (order effect of O2; p≤0.046). No such order effect was apparent for CO2 provocation (order effect of CO2; p=0.352). The group mean blood flow Coefficient of Repeatability (COR) for the narrow measurement site was 0.74 µl/min (relative to group mean flow of 4.85 µl/min ± SD 1.31) and for the wide measurement site was 1.49 µl/min (relative to group mean flow of 11.29 µl/min ± SD 3.55). There was no difference between the young and the older age groups in retinal vascular reactivity for both the narrow (two-tailed Student t-test, p=0.8692) and wide (two-tailed Student t-test, p=0.2795) measurement sites. Conclusion: This study demonstrated that the magnitude of retinal vascular reactivity was greater for arteriolar measurement sites with wider baseline vessel diameters. In addition, it demonstrated that hyperoxic provocation resulted in a persistent vasoconstriction up to 10 minutes after cessation of the stimulus. The study demonstrated that the repeatability of retinal blood flow measurements in absolute terms is lower for smaller diameter vessels. Finally, this study also suggests that age does not affect the relationship between retinal vascular reactivity and vessel diameter.

Oxygen is a necessary part of our everyday lives and is important for normal eye function. Blood flow through the retinal vasculature supplies oxygen to the inner retina. The resistance of the retinal vessels can change, increasing and decreasing blood flow by dilation and constriction of the vessel. The response of retinal hemodynamics to vasoactive stimuli is termed vascular reactivity. To investigate vascular reactivity characteristics, a system that prospectively targets a certain level of oxygen is employed. We characterize how the retinal vessels respond over time to hypoxia as well as define vascular reactivity to different oxygen concentrations in healthy participants. We demonstrate that the vessels increase diameter fully after 6 minutes and flow after 10 minutes. The relationship between retinal hemodynamics and arterial partial pressure of oxygen (PaO2) is demonstrated in healthy humans. Future studies should investigate these changes in diseased models to better understand when the retinal vasculature response may be insufficient.

Oxygen is a necessary part of our everyday lives and is important for normal eye function. Blood flow through the retinal vasculature supplies oxygen to the inner retina. The resistance of the retinal vessels can change, increasing and decreasing blood flow by dilation and constriction of the vessel. The response of retinal hemodynamics to vasoactive stimuli is termed vascular reactivity. To investigate vascular reactivity characteristics, a system that prospectively targets a certain level of oxygen is employed. We characterize how the retinal vessels respond over time to hypoxia as well as define vascular reactivity to different oxygen concentrations in healthy participants. We demonstrate that the vessels increase diameter fully after 6 minutes and flow after 10 minutes. The relationship between retinal hemodynamics and arterial partial pressure of oxygen (PaO2) is demonstrated in healthy humans. Future studies should investigate these changes in diseased models to better understand when the retinal vasculature response may be insufficient.

Made available in DSpace on 2014-06-11T19:25:26Z (GMT). No. of bitstreams: 0 Previous issue date: 2011-02-25Bitstream added on 2014-06-13T20:32:59Z : No. of bitstreams: 1 quaglio_aev_me_botib.pdf: 425313 bytes, checksum: 2483f9db556c10ebc5c1a2db7f971fa3 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / A Doença Inflamatória Intestinal (DII) engloba, fundamentalmente, duas doenças distintas: a Doença de Crohn (DC) e a Retocolite Ulcerativa (CU), ambas caracterizadas por uma inflamação crônica do intestino, com períodos de exacerbação seguidos de intervalos prolongados de remissão dos sintomas. Apesar da DII ser objeto de pesquisa há várias décadas, a sua etiologia ainda é desconhecida e a principal limitação no entendimento dos mecanismos fisiopatológicos desta doença é a disponibilidade de modelos experimentais adequados que mimetizem o caráter crônico e de recidiva da DII em humanos e que possam ser de baixo custo, reprodutível, fácil de induzir e que apresente características clínicas e histopatológicas, respostas terapêuticas e mediadores inflamatórios similares ao que ocorre com a doença em humanos. Dentre os vários modelos experimentais disponíveis, o modelo de colite induzida por ácido trinitrobenzenosulfônico (TNBS) em ratos tem sido considerado o mais adequado para a avaliação de novos fármacos, assim como aquele que melhor mimetiza esta doença em humanos. Assim sendo, a caracterização do papel de diferentes mediadores do processo inflamatório intestinal neste modelo permitiria a determinação de novos alvos terapêuticos, assim como geraria informações importantes da fisiopatologia desta doença. Neste sentido, o presente projeto teve como objetivo determinar a participação da HSP70, Heparanase e HPRT, mediadores do processo inflamatório intestinal em humanos, na fase aguda do processo inflamatório intestinal induzido TNBS em ratos, assim como estudar os efeitos de fármacos das três principais classes farmacológicas usadas no tratamento da DII em humanos, os aminossalicilatos (sulfassalazina), os glicocorticóides (prednisolona) e os imunomoduladores (azatioprina) sobre esses mediadores. Este estudo demonstrou que HSP70, Heparanase... / The idiopatic inflammatory bowel diseases comprise two types of chronic intestinal disorders: Crohn’s disease and ulcerative colitis that are characterized by a chronic inflammation of the intestine, with periods of remission and reactivation of the inflammatory process. Although IBD is the subject of research for several decades, its etiology remains unknown, and the major limitation to understanding the IBD pathophysiology is the availability of experimental models that mimic the chronic and relapse of human IBD. Is still important that experimental models can be inexpensive, reproducible, easy to induce and present clinical and histopathological features, therapeutic responses and inflammatory mediators similar to what occurs in humans. Among experimental models available, the model of colitis induced by trinitrobenzenesulphonic acid (TNBS) in rats has been considered the most suitable for the evaluation of new drugs, as well as the one that best mimics the disease in humans. Therefore, the involvement of different IBD mediators in this experimental model would allow the determination of new therapeutic targets, as well as generate important information on the pathophysiology of this disease. In light of this, the aim of present study was to determine the participation of HSP70, Heparanase and HPRT, mediators of intestinal inflammatory process in humans, in acute phase of inflammatory process induced by TNBS in rats, as well as, to study the effects of drugs of the three main classes used in the treatment of human IBD, i.e., aminosalicylates (sulphasalazine), glucocorticoids (prednisolone) and immunomodulators (azathioprine) on these mediators. This study showed that HSP70, Heparanase and HPRT participate as mediators of intestinal inflammation induced by TNBS since these mediators are increased in colitic animals when compared to healthy animals... (Complete abstract click electronic access below)

Submitted by Marcos Anselmo (marcos.anselmo@unipampa.edu.br) on 2016-09-13T19:07:13Z No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) PATRICIA MEDEIROS SCHMIDT.pdf: 1364423 bytes, checksum: 44d4424176381aef09781de156ac940d (MD5) / Approved for entry into archive by Marcos Anselmo (marcos.anselmo@unipampa.edu.br) on 2016-09-13T19:10:12Z (GMT) No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) PATRICIA MEDEIROS SCHMIDT.pdf: 1364423 bytes, checksum: 44d4424176381aef09781de156ac940d (MD5) / Made available in DSpace on 2016-09-13T19:10:12Z (GMT). No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) PATRICIA MEDEIROS SCHMIDT.pdf: 1364423 bytes, checksum: 44d4424176381aef09781de156ac940d (MD5) Previous issue date: 2015-07-31 / O alumínio (Al) é o metal mais comum da crosta terrestre, e sua elevada biodisponibilidade o torna um importante contaminante ambiental. O Al pode se acumular em vários órgãos e tem sido associado a diversas doenças, principalmente neurodegenerativas. Entretanto, pouco ainda se sabe sobre seus efeitos no sistema cardiovascular. Assim, este estudo investigou os efeitos da exposição aguda ao cloreto de alumínio (AlCl3) sobre a pressão arterial, o estresse oxidativo e a reatividade vascular de ratos. Para tal, ratos Wistar foram divididos nos grupos: Untreated: veículo (água ultrapura, ip) e AlCl3: dose única de AlCl3 (100 mg/kg ip). A pressão arterial sistólica e diastólica foi avaliada em ratos anestesiados por meio de canulação da artéria carótida imediatamente antes a administração do AlCl3 e após 1h. A reatividade de aorta foi realizada em banho de órgãos e curvas concentração resposta para acetilcolina, nitroprussiato de sódio e fenilefrina foram obtidas na presença e ausência de endotélio, L-NAME (inibidor da óxido nítrico sintase), apocinina (inibidor da NADPH oxidase), TEA (bloqueador dos canais de potássio) e SOD (scavenger de ânion superóxido). A produção de óxido nítrico (NO) foi mensurada em artérias; espécies reativas de oxigênio (EROs), malondialdeído (MDA) e níveis de tióis não-proteicos foram avaliados no plasma, assim como as atividades da superóxido dismutase (SOD), catalase, glutationa-peroxidase e glutationa-S-transferase (GST). A concentração sérica de alumínio após uma única injeção intraperitoneal de AlCl3 atingiu 147,7 ± 25,0 μg/L; esta exposição não alterou a pressão arterial, contudo induziu aos seguintes efeitos: 1) diminuição da resposta vasoconstritora à fenilefrina; 2) aumento da modulação endotelial negativa e biodisponibilidade de NO, bem como a produção de EROs vascular pela NADPH oxidase, principalmente ânions superóxido; 3) aumento dos níveis de MDA e tióis; 4) 8 maior atividade da catalase e GST 5) diminuição da atividade da SOD. Portanto, a exposição aguda ao AlCl3 promove alterações vasculares, e este efeito parece estar associado ao aumento da biodisponibilidade de NO e sua ação sobre os canais de K+, provavelmente atuando como um mecanismo compensatório sobre o estresse oxidativo. Estes resultados sugerem que o Al pode ser considerado como um agente tóxico vascular. / Aluminum (Al) is the most common metal and its high bioavailability points this as an important environmental contaminant. Aluminum can be accumulated in several organs and has been associated with several diseases, mainly neurological disorders. At cardiovascular system, there are not enough evidences of Al-induced dysfunction. We investigated the effects of acute exposure to aluminum chloride (AlCl3) on blood pressure, oxidative stress and vascular reactivity. Male Wistar rats were divided into groups: Untreated: vehicle (ultrapure water, ip) and AlCl3: single dose of AlCl3 (100 mg/kg ip). Systolic and diastolic blood pressure were assessed in anesthetized rats by cannulation of carotid artery immediately before and after one hour of aluminum administration. Aortic rings reactivity was investigated in isolated organ bath and concentration-response curves to acetylcholine, sodium nitroprusside and phenylephrine were performed in the presence and absence of endothelium, the nitric oxide synthase inhibitor L-NAME, the NADPH oxidase inhibitor apocynin, the K+ channels blocker TEA and the superoxide anion scavenger SOD. Nitric oxide (NO) released was studied in arteries; reactive oxygen species, malondialdehyde and nonprotein thiol levels were measured in plasma, as well as superoxide dismutase, catalase, glutathione peroxidase and glutathione-S-transferase activities. Serum aluminum concentration after a single intraperitoneal injection of AlCl3 reaches 147.7 ± 25.0 μg/L. This treatment did not change blood pressure, although inducing the following effects: 1) decreased vasoconstrictor response to phenylephrine; 2) increased negative endothelial modulation and nitric oxide released as well as vascular reactive oxygen species production from NADPH oxidase, mainly superoxide anions; 3) increased malondialdehyde and thiol levels; 4) enhanced catalase and glutathione-S-transferase activities and 5) decreased SOD activity. Therefore, AlCl3-acute exposure promotes vascular changes. This effect seems to be 10 associated with increased nitric oxide bioavailability, possibly acting on K+ channels, seems to occur probably as a compensatory mechanism on oxidative stress. These results suggest that this metal might be considered as a cardiovascular toxic agent.

Purpose To investigate the impact of cigarrete smoking in a group of otherwise healthy young individuals on: 1) Retinal blood flow using Doppler based SD-OCT, 2) Retinal vascular reactivity using a gas sequencer to provoke hypercapnia via constant changes in PETCO2 (end-tidal partial pressure of CO2) and in PETO2 (end-tidal partial pressure of O2). Methods An automated gas flow controller was used to achieve normoxic hypercapnia in ten non-smokers (mean age 28.9 yrs, SD 4.58) and nine smokers (mean age 27.55 yrs, SD 4.77). Retinal blood flow measurements were obtained using Doppler OCT and cannon laser blood flowmeter (CLBF) during baseline, normoxic hypercapnia (15% increase in PETCO2 relative to homeostatic baseline) and post-hypercapnia in both the groups. Exhaled carbon monoxide level was measured in all subjects. Results In non-smokers, retinal arteriolar diameter, blood velocity and flow increased by +4.1% (SD 2.8, p<0.0001), +16.7% (SD 14.6, p=0.0004) and +29.6% (SD 12.5, p<0.0001) respectively, during normoxic hypercapnia; Similarly, the venous area, venous velocity and total retinal blood flow increased by 7% (SD 8.6, p=0.0418), 18.1% (SD 20.8, p=0.0068) and 26% (SD 22.9, p<0.0001) respectively. In smokers, normoxic hypercapnia resulted in a significant increase in velocity by 12.0% (SD 6.2, p=0.0019) and flow by 14.6% (SD 9.5, p=0.0029); though arteriolar diameter increased by 1.7% (SD 1.7, p=0.2616), the result was not statistically significant. Total retinal blood flow increased significantly by 19.3% (SD 18.4, p=0.002) in response to normoxic hypercapnia. However, there was no significant difference in venous area (p=0.3322) and venous velocity measurements (p=0.1185) during hypercapnia compared to baseline and recovery. Comparing smokers and non-smokers, only the percentage change in arteriolar diameter (p=0.0379) and flow (p=0.0101) was significantly different among the groups. Group mean PETCO2 was increased by 15.9% in the non-smoking group and by 15.7% in the smoking group, with a concomitant increase in PETO2 by approximately 1.5 to 2% in both groups. There was no significant difference in baseline PETCO2 level between smokers and non-smokers. Conclusions Retinal vascular reactivity in response to normoxic hypercapnia is significantly reduced in young healthy individuals who smoke compared to non-smokers. Further studies are needed to elucidate the exact reason behind the impaired retinal autoregulation to provocative stimuli in smokers.

PURPOSE: Systemic hyperoxia has been induced using inspired gases in many studies to investigate vascular reactivity in the retinal vasculature. Technical limitations in the past resulted in inadequate control of systemic partial pressures of O2 and CO2, the latter of which tended to decrease secondary to induced hyperoxia. Recent development of a computerized gas delivery instrument has enabled the specific control of end-tidal CO2 (ETCO2) and fractional expired O2 (FeO2), independent of each other and of minute ventilation. The specific aims of each chapter are as follows: Chapter 3: To compare the magnitude and variability of the retinal vascular reactivity response to an isocapnic hyperoxic stimulus delivered using a manually-operated method to the newly developed computer-controlled gas sequencer. Chapter 4: To investigate the retinal hemodynamic response to incremental changes in hyperoxic stimuli during isocapnia. METHODS: Chapter 3: Ten young, healthy adults inhaled gases in a sequence of normoxic baseline, isocapnic hyperoxia, and normoxic recovery, using both gas delivery systems in random order. Chapter 4: Twelve healthy, young adults participated in a gas protocol consisting of 4 phases at varying fractional expired oxygen levels (FeO2): baseline (15%), hyperoxia I (40%), hyperoxia II (65%), and recovery (15%). End-tidal carbon dioxide (ETCO2) was maintained at an isocapnic level (~ 5%) throughout the experiment. In both Chapters 3 and 4, blood flow was derived from retinal arteriolar diameter and simultaneous blood velocity measurements of the superior temporal arteriole, acquired at 1-minute intervals during each of the phases of the gas protocol. RESULTS: Chapter 3: There was no interaction effect between the phases and gas delivery methods (p = 0.7718), but ETCO2 was significantly reduced during hyperoxia (p = 0.0002) for both methods. However, the magnitude of change in ETCO2 was physiologically insignificant i.e. <1%. The two systems differed in terms of FeO2 during hyperoxia, at a level of 85.27 ± 0.29% for the manual method, and 69.02 ± 2.84% for the computer method (p < 0.05). Despite this difference in oxygen concentrations, there was no difference in the vascular reactivity response for diameter (p = 0.7756), velocity (p = 0.1176), and flow (p = 0.1885) for equivalent gas phases between the two gas delivery systems. The inter-subject variability of retinal hemodynamic parameters was consistently lower using the computer-controlled gas sequencer. Chapter 4: Repeated measures ANOVA showed that there were significant influences of incremental changes in FeO2 on arteriolar diameter (p < 0.0001), blood velocity (p < 0.0001), and blood flow (p < 0.0001) in the retina. Paired t-tests of these retinal hemodynamic parameters during each phase in the gas sequence showed they were significantly different (p < 0.05) from each other, with the exception of baseline and recovery values. Incremental increases in FeO2 caused a linear decrease in group mean arteriolar diameter (R2 = 1, p = 0.002), group mean blood velocity (R2 = 0.9968, p = 0.04), and group mean blood flow (R2 = 0.9982, p= 0.03). CONCLUSIONS: Chapter 3: Inter-subject variability for virtually all retinal hemodynamic parameters was reduced using the computer-controlled method, presumably due to a higher degree of gas control. However, care needs to be exercised in the interprtetation of these results due to the relatively small sample size. A similar retinal hemodynamic response to isocapnic hyperoxia was induced using the two gas delivery systems, despite different levels of maximal FeO2. Chapter 4: Isocapnic hyperoxia elicits vasoconstriction and the reduction of retinal arteriolar blood flow in a dose-dependent manner over the range of FeO2 explored in this study.

PURPOSE: Systemic hyperoxia has been induced using inspired gases in many studies to investigate vascular reactivity in the retinal vasculature. Technical limitations in the past resulted in inadequate control of systemic partial pressures of O2 and CO2, the latter of which tended to decrease secondary to induced hyperoxia. Recent development of a computerized gas delivery instrument has enabled the specific control of end-tidal CO2 (ETCO2) and fractional expired O2 (FeO2), independent of each other and of minute ventilation. The specific aims of each chapter are as follows: Chapter 3: To compare the magnitude and variability of the retinal vascular reactivity response to an isocapnic hyperoxic stimulus delivered using a manually-operated method to the newly developed computer-controlled gas sequencer. Chapter 4: To investigate the retinal hemodynamic response to incremental changes in hyperoxic stimuli during isocapnia. METHODS: Chapter 3: Ten young, healthy adults inhaled gases in a sequence of normoxic baseline, isocapnic hyperoxia, and normoxic recovery, using both gas delivery systems in random order. Chapter 4: Twelve healthy, young adults participated in a gas protocol consisting of 4 phases at varying fractional expired oxygen levels (FeO2): baseline (15%), hyperoxia I (40%), hyperoxia II (65%), and recovery (15%). End-tidal carbon dioxide (ETCO2) was maintained at an isocapnic level (~ 5%) throughout the experiment. In both Chapters 3 and 4, blood flow was derived from retinal arteriolar diameter and simultaneous blood velocity measurements of the superior temporal arteriole, acquired at 1-minute intervals during each of the phases of the gas protocol. RESULTS: Chapter 3: There was no interaction effect between the phases and gas delivery methods (p = 0.7718), but ETCO2 was significantly reduced during hyperoxia (p = 0.0002) for both methods. However, the magnitude of change in ETCO2 was physiologically insignificant i.e. <1%. The two systems differed in terms of FeO2 during hyperoxia, at a level of 85.27 ± 0.29% for the manual method, and 69.02 ± 2.84% for the computer method (p < 0.05). Despite this difference in oxygen concentrations, there was no difference in the vascular reactivity response for diameter (p = 0.7756), velocity (p = 0.1176), and flow (p = 0.1885) for equivalent gas phases between the two gas delivery systems. The inter-subject variability of retinal hemodynamic parameters was consistently lower using the computer-controlled gas sequencer. Chapter 4: Repeated measures ANOVA showed that there were significant influences of incremental changes in FeO2 on arteriolar diameter (p < 0.0001), blood velocity (p < 0.0001), and blood flow (p < 0.0001) in the retina. Paired t-tests of these retinal hemodynamic parameters during each phase in the gas sequence showed they were significantly different (p < 0.05) from each other, with the exception of baseline and recovery values. Incremental increases in FeO2 caused a linear decrease in group mean arteriolar diameter (R2 = 1, p = 0.002), group mean blood velocity (R2 = 0.9968, p = 0.04), and group mean blood flow (R2 = 0.9982, p= 0.03). CONCLUSIONS: Chapter 3: Inter-subject variability for virtually all retinal hemodynamic parameters was reduced using the computer-controlled method, presumably due to a higher degree of gas control. However, care needs to be exercised in the interprtetation of these results due to the relatively small sample size. A similar retinal hemodynamic response to isocapnic hyperoxia was induced using the two gas delivery systems, despite different levels of maximal FeO2. Chapter 4: Isocapnic hyperoxia elicits vasoconstriction and the reduction of retinal arteriolar blood flow in a dose-dependent manner over the range of FeO2 explored in this study.