Thesis (M. Sc.)--Carleton University, 1996. / Also available in electronic format on the Internet.

Emergent epizootics are responsible for dramatic declines in wildlife populations over the past few years. An emerging fungal-borne epizootic, called white-nose syndrome (WNS), is responsible for a catastrophic decline of hibernating bats in North America The fungus, Pseudogymnoascus destructans (Pd), is the causative agent of WNS, but to date, we have limited understanding of how an infection with Pd can lead to mortality in hibernating bats. Evidence suggests dehydration is an important part of the pathogenesis of WNS. Cryan et al. (2010) proposed four possible mechanisms by which infection could lead to dehydration. In this study, I tested one of these hypotheses - Pd infection could cause disruption to passive gas-exchange pathways across the wing membranes, thereby causing a compensatory increase in water-intensive pulmonary respiration. I hypothesized total evaporative water loss would be greater when passive gas-exchange was inhibited, especially at low ambient temperatures. I found that bats did not lose more water when passive gas-exchange was retarded (at least within the resolution of my equipment). This study provides evidence against the proposed proximal mechanism that disruption to passive gas-exchange causes dehydration and ultimately death to WNS-infected bats.

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.

Hypoxia-inducible factor- 1α (HIF-1α) is a transcription factor that directs many of the cellular responses to hypoxia. In these studies, we have used a mouse model containing a cardiac-specific, oxygen-stabilized, doxycycline (Dox)-off regulated HIF-1α transgene to probe the role of HIF-1α in cardioprotection. Hearts used in these studies were derived from wild-type (WT), noninduced (Non-I), and 2 day (2D) and 6 day (6D) Dox-deprived mice. Whereas HIF-1α protein is undetectable in WT mice, it is present in heart tissue of "noninduced" transgenic mice, presumably because of leakiness of the promoter construct. In mice denied Dox for 2 or 6 days, HIF-1α is overexpressed to a much greater extent than Non-I or WT animals, as expected. WT and HIF-1α- expressing hearts (Non-I, 2D and 6D induced) were subjected to 30 min of ischemia, and functional recovery was measured upon reperfusion. Recovery of preischemic left ventricular developed pressure was 14% for WT, 67% for Non-I hearts, 64% for 2D-induced, and 62% for 6D-induced hearts. 6D-induced HIF hearts have increased preischemic glycogen reserves, higher glycogen synthase protein levels, and significantly higher lactic acid release during ischemia. 6D-induced HIF hearts were also better able to maintain ATP levels during ischemia compared with WT and Non-I hearts. Interestingly, Non-I hearts showed no significant increase in glycogen reserves, glycolytic flux, or greater ATP preservation during ischemia and yet were protected to a similar extent as the 6D-induced hearts. Finally, the mitochondrial membrane potential of isolated adult myocytes was monitored during anoxia or treatments with cyanide and 2-deoxyglucose. HIF-1α expression was shown to protect mitochondrial polarization during both stress treatments. Taken together these data indicate that, while HIF-1α expression in heart does induce increases in compensatory glycolytic capacity, these changes are not necessarily required for cardioprotection, at least in this model of ischemic stress.

Hypoxia-inducible factor- 1α (HIF-1α) is a transcription factor that directs many of the cellular responses to hypoxia. In these studies, we have used a mouse model containing a cardiac-specific, oxygen-stabilized, doxycycline (Dox)-off regulated HIF-1α transgene to probe the role of HIF-1α in cardioprotection. Hearts used in these studies were derived from wild-type (WT), noninduced (Non-I), and 2 day (2D) and 6 day (6D) Dox-deprived mice. Whereas HIF-1α protein is undetectable in WT mice, it is present in heart tissue of "noninduced" transgenic mice, presumably because of leakiness of the promoter construct. In mice denied Dox for 2 or 6 days, HIF-1α is overexpressed to a much greater extent than Non-I or WT animals, as expected. WT and HIF-1α- expressing hearts (Non-I, 2D and 6D induced) were subjected to 30 min of ischemia, and functional recovery was measured upon reperfusion. Recovery of preischemic left ventricular developed pressure was 14% for WT, 67% for Non-I hearts, 64% for 2D-induced, and 62% for 6D-induced hearts. 6D-induced HIF hearts have increased preischemic glycogen reserves, higher glycogen synthase protein levels, and significantly higher lactic acid release during ischemia. 6D-induced HIF hearts were also better able to maintain ATP levels during ischemia compared with WT and Non-I hearts. Interestingly, Non-I hearts showed no significant increase in glycogen reserves, glycolytic flux, or greater ATP preservation during ischemia and yet were protected to a similar extent as the 6D-induced hearts. Finally, the mitochondrial membrane potential of isolated adult myocytes was monitored during anoxia or treatments with cyanide and 2-deoxyglucose. HIF-1α expression was shown to protect mitochondrial polarization during both stress treatments. Taken together these data indicate that, while HIF-1α expression in heart does induce increases in compensatory glycolytic capacity, these changes are not necessarily required for cardioprotection, at least in this model of ischemic stress.

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In the temperate region, bats have evolved the strategy of hibernation to survive the harsh winter. During hibernation, bats enter the vulnerable state of torpor that requires specific environmental conditions to function optimally. Bats are known to use caves and anthropogenic structures as hibernation sites. However, the majority of the bat population cannot be accounted for when such structures are surveyed. There is evidence that bats use other natural structures as hibernation sites. To examine bat’s choices of hibernation sites and activity, acoustic monitoring of bats in south-west Sweden was performed during the winter of 2022-2023. Bat activity was measured in areas with potential hibernation sites in natural structures (rock outcrops), as well as inside and outside of known hibernation sites (anthropogenic structures). The level of activity and the ambient temperature were tested for a possible correlation. Additionally, data from 2006-2022 of surveys of bats in hibernation sites were examined for a possible relationship with outside ambient temperature. Bats were found to be active during the winter inside the known sites of hibernation. There was also activity recorded outside one of the known hibernation sites, but no bat activity was found in the areas of potential hibernation sites. No significant correlation was shown between bat activity and outside temperature, nor between number of bats inside a hibernation site and outside temperature. Further research is needed to develop the knowledge about bats’ hibernation behavior which in turn will aid more effective conservation of temperate bat species.

Faktoren, die die funktionelle Erholung von hibernating myocardium nach aortokoronarem Venen Bypass (ACVB) beeinflussen, werden gegenwärtig untersucht. Von 3/2000 bis 3/2003 untersuchten wir prospektiv 41 Patienten mit einer linksventrikulären Ejektionsfraktion (LVEF) / Objectives: Factors that influence functional recovery of hibernating myocardium after coronary artery bypass grafting are at present under investigation. Methods: From 3/2000 to 3/2003 we prospectively analyzed 41 patients with ejection fraction (EF) 15% during DE in group I preoperatively; the increase was < 15% in group II. MRI hyperenhancement was measured with a mean of 16,7±11,6% of the left ventricle in group I compared to a mean of 27,4±14,4% in group II (p 19µm) in group I than in group II (< 17µm). Gene expression of pro-apoptotic genes such as BAK and BAX was lowered (0.5±0.1/0.8±0.1) compared to "normal" myocardium (1.0±0.1) (p