Mechanisms of ischemia-induced ST-segment changes.
Many aspects of ischemia-induced changes in the electrocardiogram lack solid biophysical underpinnings although variations in ST segments form the predominant basis for diagnostic and monitoring of patients. This incomplete knowledge certainly plays a role in the poor performance of some forms of electrocardiogram-based detection and characterization of ischemia, especially when it is limited to the subendocardium. The focus of our recent studies has been to develop a comprehensive mechanistic model of the electrocardiographic effects of ischemia. The computational component of this model is based on highly realistic heart geometry with anisotropic fiber structure and allows us to assign ischemic action potentials to contiguous regions that can span a prescribed thickness of the ventricles. A separate, high-resolution model of myocardial tissue provides us with a means of setting electrical characteristics of the heart, including the status of gap junctional coupling between cells. The experimental counterpart of this model consists of dog hearts, either in situ or isolated and perfused with blood, in which we control coronary blood flow by means of a cannula and blood pump. By reducing blood flow through the cannula for various durations, we can replicate any phase of ischemia from hyper acute to early infarction. Based on the results of these models, there is emerging a mechanism of the electrocardiographic response to ischemia that depends strongly on the anisotropic conductivity of the myocardium. Ischemic injury currents flow across the boundary between healthy and ischemic tissue, but it is their interaction with local fiber orientation and the associated conductivity that generates secondary currents that determine epicardial ST-segment potentials. Results from experiments support qualitatively the findings of the simulations and underscore the role of myocardial anisotropy in electrocardiography.
MacLeod
Robert S
RS
Bioengineering Department, University of Utah, Salt Lake City, Utah 84112-5000, USA. macleod@cvrti.utah.edu
Shome
Shibaji
S
Stinstra
Jeroen
J
Punske
Bonnie B
BB
Hopenfeld
Bruce
B
D000818:Animals; D003326:Coronary Circulation; D004195:Disease Models, Animal; D004285:Dogs; D004558:Electric Stimulation; D004562:Electrocardiography; D006329:Heart Conduction System / Q000503:physiopathology*; D008955:Models, Cardiovascular; D017202:Myocardial Ischemia / Q000503:physiopathology*; D014655:Vascular Resistance