This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Drug induced torsades de pointes is a potentially fatal complication associated with the use of various cardiac and non-cardiac medications. While various formulas may prove useful in evaluation of individual patients with concerns for a prolonged QT interval, these have been shown to be unreliable for use in large populations, making the evaluation of drug safety difficult. The heart rate is an integral part of QT interval correction, and has various mediators including both autonomic and intrinsic influences. To date, while various studies have evaluated QT prolonging drug effects on heart rate and QT intervals, the effects of QT prolonging drugs in the absence of autonomic influences has not been explored. We propose to evaluate the QT prolonging drug ibutilide and its effects on intrinsic heart rate and QT intervals after achieving pharmacologic autonomic block. Assessing intrinsic heart rate and QT interval response to a known QT prolonging agent may prove useful in delineating autonomic versus intrinsic sinus node contributions to drug-induced torsades de pointes.
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