Vasculogenic cell-based therapy combined with tissue engineering is a promising revascularization strategy for patients with hibernating myocardium, a common clinical condition. We used a clinically relevant swine model of hibernating myocardium to examine the benefits of biopolymer-supported delivery of circulating angiogenic cells (CACs) in this context. Twenty-five swine underwent placement of an ameroid constrictor on the left circumflex artery (LCx). After 2 weeks, positron emission tomography measures of myocardial blood flow (MBF) and myocardial flow reserve (MFR) were reduced in the affected region (both p<0.001). Hibernation (mismatch) was specific to the LCx territory. Swine were randomized to receive intramyocardial injections of PBS control (n=10), CACs (n=8), or CACs + a collagen-based matrix (n=7). At follow-up, stress MBF and MFR were increased only in the cells+matrix group (p<0.01), and mismatch was lower in the cells+matrix treated animals (p=0.02) compared to controls. Similar results were found using microsphere-measured MBF. Wall motion abnormalities and ejection fraction improved only in the cells+matrix group. This preclinical swine model demonstrated ischemia and hibernation, which was improved by the combined delivery of CACs and a collagen-based matrix. To our knowledge, this is the first demonstration of the mechanisms and effects of combining progenitor cells and biopolymers in the setting of myocardial hibernation, a common clinical condition in patients with advanced coronary artery disease.

Vasculogenic cell-based therapy combined with tissue engineering is a promising revascularization strategy for patients with hibernating myocardium, a common clinical condition. We used a clinically relevant swine model of hibernating myocardium to examine the benefits of biopolymer-supported delivery of circulating angiogenic cells (CACs) in this context. Twenty-five swine underwent placement of an ameroid constrictor on the left circumflex artery (LCx). After 2 weeks, positron emission tomography measures of myocardial blood flow (MBF) and myocardial flow reserve (MFR) were reduced in the affected region (both p<0.001). Hibernation (mismatch) was specific to the LCx territory. Swine were randomized to receive intramyocardial injections of PBS control (n=10), CACs (n=8), or CACs + a collagen-based matrix (n=7). At follow-up, stress MBF and MFR were increased only in the cells+matrix group (p<0.01), and mismatch was lower in the cells+matrix treated animals (p=0.02) compared to controls. Similar results were found using microsphere-measured MBF. Wall motion abnormalities and ejection fraction improved only in the cells+matrix group. This preclinical swine model demonstrated ischemia and hibernation, which was improved by the combined delivery of CACs and a collagen-based matrix. To our knowledge, this is the first demonstration of the mechanisms and effects of combining progenitor cells and biopolymers in the setting of myocardial hibernation, a common clinical condition in patients with advanced coronary artery disease.

This thesis evaluates, in free-ranging eastern chipmunks (Tamias striatus), burrow site selection, the effect of burrow microhabitat on individual behaviour and winter torpor expression, as well as resource and climate determinants of fine-scale variation in winter torpor expression and energetics. This was accomplished by characterizing burrow microhabitat, performing behavioural observations, and monitoring winter torpor expression. Among several burrow microhabitat variables related to food availability, predation risk, and hibernacula microclimate, availability of woody debris was the best predictor of burrow site use. Anti-predator benefits associated with availability and use of woody debris are potentially more important than those associated with burrow microhabitat features that are either too spatially invariant (soil temperatures) or too spatially and temporally variant (food sources). Abundance of tree-seeds drastically reduced winter torpor, increasing considerably winter energy consumption, and local density of seed-producing trees was responsible for fine-scale spatial variation in torpor expression. The potential range in winter torpor expression and energy consumption was constrained by microclimate, whereas observed patterns of winter torpor and energy consumption were highly variable and determined primarily by local food abundance.

Small endotherms typically have elevated and relatively invariant rates of metabolism, but adaptations such as food hoarding and hibernation endow some species with considerable energetic flexibility in responding to resource fluctuations. I examined the interactions between resource availability, food hoarding, and hibernation in a population of eastern chipmunks (Tamias striatus) subjected to seasonal and multi-annual periods of resource shortage. Incompatibility of torpor and digestion could be an important constraint associated with relying on stored food rather than body fat during hibernation, but documentation of torpor patterns and digestive efficiency of captive chipmunks revealed that digestion is actually enhanced by torpor expression. Measures of energy expenditure and food delivery by free-ranging chipmunks in autumn revealed that food hoarding also permitted rapid accumulation of large energy reserves before thermoregulatory constraints necessitated termination of above-ground activity. Thus, a combination of food hoarding and hibernation permits rapid energy accumulation when resources are abundant and effective energy conservation when resources are scarce. Despite this, chipmunks responded to experimental increases of autumn hoard size by substantially reducing winter torpor expression, suggesting that much of the resource accumulation permitted by larder hoarding is allocated to maintaining elevated rates of metabolism in the winter hibernaculum. This pattern of allocation suggests torpor expression is associated with important costs and contradicts a major paradigm of hibernation research by demonstrating that low levels of torpor expression can reflect an absence of energetic necessity rather than a lack of physiological capability. In an ecological context, the capacity of chipmunks to vary expenditure according to resource abundance represents a potent decoupling mechanism in consumer-resource interactions. Energetic flexibility of this form

Vasculogenic cell-based therapy combined with tissue engineering is a promising revascularization strategy for patients with hibernating myocardium, a common clinical condition. We used a clinically relevant swine model of hibernating myocardium to examine the benefits of biopolymer-supported delivery of circulating angiogenic cells (CACs) in this context. Twenty-five swine underwent placement of an ameroid constrictor on the left circumflex artery (LCx). After 2 weeks, positron emission tomography measures of myocardial blood flow (MBF) and myocardial flow reserve (MFR) were reduced in the affected region (both p<0.001). Hibernation (mismatch) was specific to the LCx territory. Swine were randomized to receive intramyocardial injections of PBS control (n=10), CACs (n=8), or CACs + a collagen-based matrix (n=7). At follow-up, stress MBF and MFR were increased only in the cells+matrix group (p<0.01), and mismatch was lower in the cells+matrix treated animals (p=0.02) compared to controls. Similar results were found using microsphere-measured MBF. Wall motion abnormalities and ejection fraction improved only in the cells+matrix group. This preclinical swine model demonstrated ischemia and hibernation, which was improved by the combined delivery of CACs and a collagen-based matrix. To our knowledge, this is the first demonstration of the mechanisms and effects of combining progenitor cells and biopolymers in the setting of myocardial hibernation, a common clinical condition in patients with advanced coronary artery disease.

Thesis (Ph. D.)--Carleton University, 2002. / Includes bibliographical references (p. 166-178). Also available in electronic format on the Internet.

Thesis (M. Sc.)--Carleton University, 2004. / Includes bibliographical references (p. 147-165). Also available in electronic format on the Internet.

Thesis (M. Sc.)--Carleton University, 2004. / Includes bibliographical references (p. 119-132). Also available in electronic format on the Internet.

Thesis (M.Sc.) - Carleton University, 2005. / Includes bibliographical references (p. 134-145). Also available in electronic format on the Internet.

Thesis (M.SC.) - Carleton University, 2007. / Includes bibliographical references (p. 92-103). Also available in electronic format on the Internet.