With the aging population on the rise, the prevalence of heart failure is expected to increase in the coming years. Heart failure is independently correlated with cognitive decline and has a negative impact on quality of life, morbidity and mortality. Reduced cardiac output (Q) and cerebral blood flow (CBF) are proposed mechanistic links between heart failure and cognitive decline; however, reports are limited to the supine position and the response to an everyday upright posture is unknown. The purpose of this thesis was to primarily investigate the CBF response to a common upright seated position encountered in daily life in heart failure patients compared to healthy age- and sex-matched controls. Furthermore, we sought to determine whether cognitive performance or cognitive-activated hemodynamics were posture-dependent in the heart failure group. The secondary objective of this thesis was to be inclusive to patients that represent those encountered in clinical practice???specifically to include patients with higher left ventricular ejection fractions (LVEF) and atrial fibrillation with co-existing heart failure. Our findings confirmed greater cognitive impairments and a low supine CBF and Q in heart failure compared to controls and importantly, for the first time, a greater reduction in CBF with an upright seated position compared to healthy age- and sex- matched controls. When a cognitive task was performed supine and seated, performance outcomes were independent of posture in heart failure patients. However, mean flow velocity through the middle cerebral artery (MFV_MCA) increased less in response to the cognitive task seated. With regard to our secondary objectives, the results suggest that those with higher LVEF are equally at risk for cognitive decline and cerebral hypoperfusion due to a low Q. Furthermore, high variability in Q and MFV_MCA were detected in association with the beat-to-beat variation inherent to atrial fibrillation and suggest that this may be an underappreciated pathway to cognitive impairments in this sub-group. Together, these results suggest that upright cerebral hypoperfusion throughout the day may contribute to cognitive decline in heart failure and create a basis for further work to be done with larger sample sizes. Moreover, cerebral hypoperfusion with higher LVEF and the blood flow variation in atrial fibrillation represent important pathways contributing to cognitive decline in these under investigated sub-groups.

Purpose: To investigate venous total retinal blood flow (TRBF) and retinal blood flow (RBF) in the superior and the inferior retinal hemifields in primary open angle glaucoma (POAG) patients with, and without, disc hemorrhage (DH). Methods: RBF measurements were obtained from 10 POAG with DH and 19 POAG without DH using Doppler SD-OCT (RTVue) as well as bi-directional laser Doppler flowmetry (CLBF). Results: RBF was not different between the superior and inferior hemifields for either of the two groups. Venous TRBF in the POAG with DH group was significantly lower than in the age-matched stable POAG without DH group (p=0.009). In the POAG with DH group, venous TRBF was significantly lower in the DH eye compared to contralateral eye without DH (p=0.015). Conclusions: Venous TRBF was significantly lower in the POAG with DH group compared to both the POAG without DH group and the contralateral eye of the POAG with DH group.

Purpose: To investigate venous total retinal blood flow (TRBF) and retinal blood flow (RBF) in the superior and the inferior retinal hemifields in primary open angle glaucoma (POAG) patients with, and without, disc hemorrhage (DH). Methods: RBF measurements were obtained from 10 POAG with DH and 19 POAG without DH using Doppler SD-OCT (RTVue) as well as bi-directional laser Doppler flowmetry (CLBF). Results: RBF was not different between the superior and inferior hemifields for either of the two groups. Venous TRBF in the POAG with DH group was significantly lower than in the age-matched stable POAG without DH group (p=0.009). In the POAG with DH group, venous TRBF was significantly lower in the DH eye compared to contralateral eye without DH (p=0.015). Conclusions: Venous TRBF was significantly lower in the POAG with DH group compared to both the POAG without DH group and the contralateral eye of the POAG with DH group.

No description available.

No description available.

Little is known of the temporal cerebral blood flow response to a chemical stimulus consisting of increased PCO2 measured over time. Currently, there is only one study suggesting multiple phases in the CBF-CO2 response. Time constants of middle cerebral artery blood velocity (MCAV) response to a change in PETCO2 have been reported to be between 3 and 99.4 s. We studied the MCAV response in 28 subjects (10 females) to a sustained +10 mmHg above baseline (10 min) acute increase of PETCO2. We found that there were three distinct MCAV response patterns among subjects. Additionally, the responses of males and females differed. These studies suggest that there are multiple overlapping mechanisms controlling the chemoresponse of cerebral blood vessels and that these mechanisms may differ between men and women.

This thesis describes experiments to measure the ventilatory response to hypoxia at a constant (isocapnic) level of CO2 (HVR) in 18 subjects. So as to provide a complete picture of the autonomic responses, middle cerebral artery velocity, a surrogate for cerebral blood flow (CBF), as well as finger plethysmography blood pressure (BP) were also measured. Ventilatory responses have been previously described only in terms of an acute peak followed by a decline. However, rather than a single type of response, I found four types categorized as: Decline, Double, Plateau, or No response. The Double pattern, characterized by a second peak of response was the most common, yet is described here for the first time. These patterns are also characteristic of the CBF and BP responses. Furthermore the temporal correlations between these brainstem-controlled responses are also reported here for the first time.

Little is known of the temporal cerebral blood flow response to a chemical stimulus consisting of increased PCO2 measured over time. Currently, there is only one study suggesting multiple phases in the CBF-CO2 response. Time constants of middle cerebral artery blood velocity (MCAV) response to a change in PETCO2 have been reported to be between 3 and 99.4 s. We studied the MCAV response in 28 subjects (10 females) to a sustained +10 mmHg above baseline (10 min) acute increase of PETCO2. We found that there were three distinct MCAV response patterns among subjects. Additionally, the responses of males and females differed. These studies suggest that there are multiple overlapping mechanisms controlling the chemoresponse of cerebral blood vessels and that these mechanisms may differ between men and women.

This thesis describes experiments to measure the ventilatory response to hypoxia at a constant (isocapnic) level of CO2 (HVR) in 18 subjects. So as to provide a complete picture of the autonomic responses, middle cerebral artery velocity, a surrogate for cerebral blood flow (CBF), as well as finger plethysmography blood pressure (BP) were also measured. Ventilatory responses have been previously described only in terms of an acute peak followed by a decline. However, rather than a single type of response, I found four types categorized as: Decline, Double, Plateau, or No response. The Double pattern, characterized by a second peak of response was the most common, yet is described here for the first time. These patterns are also characteristic of the CBF and BP responses. Furthermore the temporal correlations between these brainstem-controlled responses are also reported here for the first time.

Exercise and/or heat-induced dehydration is associated with decreases in plasma volume (hypovolemia) and increases in plasma osmolality (hyperosmolality), which are thought to stimulate peripheral baroreceptors and central osmoreceptors respectively. Independently, plasma hyperosmolality and baroreceptor unloading have been shown to attenuate sweating and cutaneous vasodilation during heat stress, and therefore, negatively impact body temperature regulation. However, to date little is known regarding the combined influence of plasma hyperosmolality and baroreceptor unloading on thermoefferent activity. Therefore, we evaluated the separate and combined effects of baroreceptor unloading (via lower body negative pressure, LBNP) and plasma hyperosmolality (via infusion of 3% NaCl saline) on heat loss responses of sweating and cutaneous vascular conductance (CVC) during progressive whole-body heating. We show that the combined nonthermal influences of plasma hyperosmolality and baroreceptor unloading additively delay the onset threshold for CVC, relative to their independent effects. In contrast, baroreceptor unloading has no influence on the sweating response regardless of osmotic state. These divergent roles of plasma hyperosmolality and the baroreflex on heat loss responses might serve to enhance blood pressure and body core temperature regulation during dehydration and heat stress.