The interaction between the mapping/ablation catheter and left atrial (LA) myocardium potentially affects the LA electrical and mechanical properties and impacts on ablation efficacy. Using catheters able to provide real-time contact force (CF) measurement, it has become possible to explore these relationships in vivo. In 60 persistent atrial fibrillation (AF) patients, ablation CF was higher in the right than left wide area circumferential (WACA) lines and where steerable transseptal sheaths were used. Differences were also apparent in the burden of WACA segment reconnection but did not just reflect differences in ablation CFs, suggesting factors other than CF contribute to ablation efficacy. Relationships between ablation force time integral (FTI), impedance drop and electrogram attenuation were assessed in 15 persistent AF patients. FTI significantly correlated with electrogram attenuation and impedance drop from ablation. The relationship was stronger for the former but in both cases plateaued at 500g.s, suggesting no ablation efficacy gains beyond this. Factors further affecting CF and ablation efficacy, the latter judged by impedance drop, were assessed in 30 patients. The variability of the CF waveform and catheter locational stability were both affected by factors including atrial rhythm and catheter delivery mode. Greater CF variability, catheter drift and perpendicular catheter contact were associated with reduced ablation efficacy. The relationship between CF and the electrogram was assessed in 30 patients. The size of the electrogram complexes was affected by CF increases but only where initial CF was <10g. This was also the case for electrogram fractionation measurements. Increasing CF was associated with an increasing incidence of atrial ~ 3 ~ ectopics during sinus rhythm. Spectral parameters (dominant frequency and organisation index) were unaffected by CF. Various factors affect the contact between the catheter and LA myocardium. In turn, catheter contact significantly affects the electrogram during LA mapping and the efficacy of clinical radiofrequency ablation.

Thesis (Ph. D.)--University of Chicago, Dept. of Molecular Genetics and Cell Biology, August 2003. / CD-ROM reproduces dissertation in PDF format; Adobe Acrobat required. Includes bibliographical references. Also available on the Internet.

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

published_or_final_version / Anatomy / Doctoral / Doctor of Philosophy

Rapid restoration of blood flow to ischemic myocardium is essential, however it causes further injury called reperfusion injury. Apoptosis contributes significantly to cardiomyocyte cell death during ischemia reperfusion injury, in which caspase family proteases play an essential role as they are the executioners of apoptosis. Caspase inhibitors showed promising cardioprotective results when administered before ischemia or at the start of reperfusion. However, before applying them in pre clinical studies of myocardial ischemia, several investigations needed to be taken to determine their therapeutic window post reperfusion, their effect on functional recovery of myocardium post ischemia, their mechanism of action. Methods Isolated perfused rat hearts were subjected to 35 min ischemia followed by 2 hr reperfusion where caspase inhibitors [broad spectrum caspase inhibitor (ZVAD, 0.1µM), specific caspase 3 inhibitor (DEVD, 0.07µM)] were added at the start of reperfusion, 15, 30 and 60 min after starting reperfusion at the presence or absence of Wortmannin (WORT, 100nM, PI3-kinase inhibitor). Hearts underwent triphenyl tetrazolium staining for infarct size assessment, or were frozen for Western blot analysis. Freshly isolated adult rat ventricular myocytes were subjected to 6 hr hypoxia followed by either 18 hr, where caspase inhibitors (ZVAD, 25µM and DEVD, 25µM) were added at the start of reoxygenation, 15, 30 and 60 min after starting reoxygenation at the presence or absence of Wortmannin (WORT, 100nM). Cardiomyocytes were analysed for viability, apoptosis, necrosis and intracellular caspase-3 activity using flow cytometry analysis. Isolated adult rat ventricular papillary muscles were subjected to 35 min hypoxia followed by 100 min reperfusion where caspase inhibitors [ZVAD (0.1 µM, 2.5µM) and DEVD (2.5µM)] were added at the start of reperfusion throughout. Power output was measured using work loop technique.

published_or_final_version / Physiology / Master / Master of Philosophy

Dissertation (PhD)--University of Stellenbosch, 2007. / Bibliography. Also available via the Internet.

Thesis (M.S.)--Oregon State University, 2008. / Printout. Includes bibliographical references (leaves 114-119). Also available on the World Wide Web.

Dissertation (Ph.D.)--Auburn University, 2006. / Abstract. Vita. Includes bibliographic references.

Thesis (Ph.D.)--University of Delaware, 2007. / Principal faculty advisor: Ulhas Naik, Dept. of Biological Sciences. Includes bibliographical references.