Russell McEvoy, Gaylene M. (2024) Quantifying microvascular hemodynamics in healthy and type 2 diabetic rats. Doctoral (PhD) thesis, Memorial University of Newfoundland.
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Abstract
The human circulatory system is composed of a branching vascular tree giving rise to the microcirculation which serves as the major site of exchange between the blood and tissues. Blood flow distribution among microvascular networks is dynamically controlled to match the supply of oxygen and nutrients, such as glucose, with the demands of the tissues. Diabetes Canada estimates that 1 in 3 Canadians are living with diabetes or prediabetes, and up to 90 to 95% of those living with diabetes are type 2 diabetic. Evidence in the literature suggests the response to insulin is blunted in type 2 diabetes (T2D) and insulin resistant individuals due to endothelial dysfunction. We hypothesized that chronic hyperglycemia and elevated insulin in T2D impairs oxygen mediated blood flow regulation leading to functional defects in capillary network blood flow distribution at rest, in response to oxygen challenges, and during hyperinsulinemia. To test this hypothesis 15- and 27-week-old Sprague Dawley (SD) and Zucker Diabetic Sprague Dawley (ZDSD) rats were fed a normal fat, high fat, or high-sugar high-fat diet, anaesthetized with sodium pentobarbital, mechanically ventilated, and instrumented for systemic monitoring and fluid resuscitation. The extensor digitorum longus muscle was blunt dissected and reflected over a glass coverslip or a gas exchange chamber set in the stage of an inverted microscope. Intravital video microscopy recordings were made during baseline, hyperinsulinemia, and acute changes in local O₂ concentration ([O₂]). Further, in 7-week-old SD rats we quantified the dynamics of capillary hemodynamic responses to changes in tissue [O₂] and CO₂ concentration ([CO₂]) analogous to expected changes at the onset of moderate exercise. We determined that hyperinsulinemic-euglycemic clamp increased capillary hemodynamics and red blood cell oxygen saturation in SD rats; however, there was no response to systemic hyperinsulinemia in ZDSD rats. 27-week-old SD and ZDSD rats had impaired capillary hemodynamic responses to changes in [O₂] following high-fat high-sugar feeding. We quantified profound differences in the dynamics of hemodynamic responses to altered [O₂] and [CO₂] in skeletal muscle which are additive in young healthy SD rats. This demonstrates that prolonged high-fat feeding and T2D lead to functional changes in oxygen reactivity in capillary hemodynamic responses.
| Item Type: | Thesis (Doctoral (PhD)) |
|---|---|
| URI: | http://research.library.mun.ca/id/eprint/16575 |
| Item ID: | 16575 |
| Additional Information: | Includes bibliographical references (pages 260-290) -- Restricted until July 31, 2026 |
| Keywords: | capillary hemodynamics, microcirculation, type 2 diabetes, obesity, oxygen mediated blood flow |
| Department(s): | Medicine, Faculty of > Biomedical Sciences |
| Date: | October 2024 |
| Date Type: | Submission |
| Medical Subject Heading: | Diabetes Mellitus, Type 2; Microcirculation; Rats; Capillaries; Diet, High-Fat; Hemodynamics; Hyperglycemia; Canada |
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