Localized spontaneous activation of cardiac tissue during acute ischemia and reperfusion

Matthew Kay, PE, D.Sc.
Narine Sarvazyan, Ph.D.
The George Washington University

In the United States almost 6.5 million people suffer from coronary heart disease. Episodic angina is newly diagnosed in about 350,000 people each year, with ischemia episodes becoming more frequent as constriction of a coronary artery worsens. During ischemia a sequence of biochemical events is initiated that ultimately leads to cellular dysfunction and necrosis. When blood flow is restored, additional biochemical insults ensue, compounding the injury. Thus, whenever there is a transient decrease or interruption of blood flow, the net injury is the sum of two components - the direct injury occurring during the ischemia and the indirect, or reperfusion injury, which follows. This repetitive ischemia and reperfusion can cause premature beats, sustained arrhythmias, and is thought to be a significant cause of sudden cardiac death.
We have studied the incidence of localized, spontaneous activation of cardiac tissue (premature beats) in rat hearts during acute regional ischemia and reperfusion. We cannulate the left anterior descending coronary artery to provide for independent control of flow to a specific tissue bed. Dual epicardial fluorescence imaging of transmembrane potential and mitochondrial redox state (NADH) is used to record activation sequences as well as the geometry of the ischemic zone at high spatiotemporal resolution. The timing and locations of premature beats are identified and the temporal progression of ischemia is monitored. During ischemia and full-flow reperfusion we have observed that premature beats arise from the border between normal and ischemic tissue. During low-flow reperfusion we have found that the number of premature beats and their spatial dispersion increases dramatically, with most premature beats located within the ischemic bed. Local changes in NADH during low-flow reperfusion revealed a slow recovery of small patches of ischemic tissue and large spatial gradients, indicating the formation of new ischemic boundary zones. We have concluded that a strong correlation exists (p<0.01) between the location of premature beats and the spatial gradient of the change in mitochondrial redox state caused by reperfusion.

[Talk Slides]

Biography:
Matthew Kay, PE, D.Sc., received a Bachelors and Masters degree from North Carolina State University. In 2000 he received a Doctorate degree in Biomedical Engineering from Washington University in St. Louis. He completed Post-Doctoral training at the University of Alabama in Birmingham. Dr. Kay was a research assistant professor at UAB and in the Dept. of Pharmacology and Physiology at The George Washington University before joining the Dept. of Electrical and Computer Engineering at GWU as an Assistant Professor.

Dr. Kay's research is primarily focused upon understanding cardiac electrical activity during normal and disease conditions - with an overall goal of improving heart disease therapies. His expertise is in fluorescence and electrical imaging of heart tissue and cultures of cardiac cells. He uses custom image processing algorithms and computational models to test hypotheses and identify mechanisms of cardiac electrical pathologies. His recent studies have focused upon identifying ischemic mechanisms of ectopic arrhythmias.