Gene expression in cardiac surgery
Subtitle: impact of ischemia and reperfusion.
Published: 2004
Language: eng
Number of pages: 204
Description: Ischemia and reperfusion (IR) invariably occurs during cardiac surgery. However, the transcriptional regulation of the myocardial and leukocyte genome in IR injury is incompletely elucidated. The primary hypothesis of this thesis is that IR injury occurring during cardiac surgery results in rapid induction of a specific pattern of gene transcription. The secondary hypothesis concerns the genomic and physiologic responses to protective brief periods of IR applied to the tissue located remotely from the heart (i.e., by a remote ischemic preconditioning (rIPC) stimulus). Gene expression was assessed primarily using microarray technology. In an initial study, we observed up-regulation of genes with possible cytoprotective functions in neonatal myocardium during ischemia. Global human myocardial gene expression during intra-operative IR injury was determined in a second study. A series of studies were then designed to examine the genomic and functional responses to a clinically-relevant rIPC stimulus. As leukocytes play a key role in IR injury, we identified the global genomic changes in human leukocytes following the rIPC stimulus. We then examined myocardial genomic responses in a mouse model, and, finally, demonstrated a major protective effect of rIPC in a porcine model of cardiopulmonary bypass (CPB) and intra-operative IR injury. Based on these data we applied the rIPC clinically with encouraging preliminary results.Overall the results of these studies indicate that intra-operative myocardial IR injury results in rapid induction of gene expression, and that this genomic response appears to be age-specific and can be modified by rIPC.
Notes: Adviser:  John G. Coles.

Thesis (Ph.D.)--University of Toronto, 2004.

Electronic version licensed for access by U. of T. users.

Source: Dissertation Abstracts International, Volume: 65-10, Section: B, page: 5065.