The focus of this project is the detailed measurement of ventricular repolarization in animal models of human disease. The overall objective of Subproject 4.1, Ventricular Repolarization in a Rapid Pacing Induced Canine Model of Heart Failure, is to study the distribution and rate related changes of repolarization in canine hearts compromised by rapid pacing induced heart failure. Emphasis of the research is directed at determining the ability of body surface measurements to reflect details of repolarization characteristics as directed at determining the ability of body surface measurements to reflect details of repolarization characteristics as measured directly from epicardial and intramural regions. The overall aim of Subproject 4.2, Ventricular Repolarization in Canine Models of LQT Syndrome, is to study repolarization in isolated, Langendorff perfused canine hearts suspended in a torso-shaped tank during control states and following pharmacological interventions that mimic genotypically characterized LQT syndromes. The main goals of this research are to characterize the three-dimensional nature of repolarization changed induced by these interventions and to assess the ability of non-invasive (body surface) measurement to reflect in detail the characteristics of abnormal repolarization. The underlying premise of this research is one of the themes of the SCOR-that a major factor in sudden cardiac death is an underlying pro- arrhythmic substrate of heterologous repolarization characteristics. The resulting need that drives this particular project is the lack of consistent, reliable, reliable, and sensitive non-invasive indices of repolarization. We propose to build on and extend the methodologies developed in the present cycle of the SCOR and apply them under realistically pro- arrhythmic models in canines. The results will allow us to define the limits to which repolarization characteristics, as measured directly at the heart, are detectable on the body surface. The clinical significance of the work lies in the development and assessment of electrocardiographic techniques that can be Applied direct to humans to improve the detection and monitoring of repolarization abnormalities that may contribute to sudden death.
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