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Angerlike behavioral state potentiates myocardial ischemia-induced T-wave alternans in canines

Julie A. Kovach, MD, FACC^*, Bruce D. Nearing, PhD and Richard L. Verrier, PhD, FACC

^* Department of Internal Medicine, Division of Cardiology, University of Michigan, Ann Arbor, Michigan, USA
Institute for Prevention of Cardiovascular Disease, Department of Medicine, Division of Cardiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA

View larger version (14K): [in a new window]   Figure 1 T-wave alternans magnitude increased significantly from baseline (0.04 ± 0.02 mV x ms) during induction of an angerlike behavioral state alone (to 1.40 ± 0.32, p < 0.05) and with simultaneous myocardial ischemia and angerlike response (to 3.27 ± 0.61, p < 0.05). The 3-min periods of ischemia were insufficient to increase T-wave alternans significantly from baseline (to 0.67 ± 0.09 mV x ms, p = NS). Concurrent provocation of the angerlike state and imposition of myocardial ischemia increased T-wave alternans magnitude in excess of their additive effects (p < 0.05). This amplification was blunted by beta-adrenergic blockade with metoprolol (p < 0.0004 for all), which reduced T-wave alternans at baseline (to 0.04 ± 0.01) during the angerlike state (to 0.80 ± 0.17) during myocardial ischemia (to 0.55 ± 0.11) and during simultaneous myocardial ischemia and angerlike response (to 1.23 ± 0.13). Open bars = no drug; solid bars = metoprolol. *p < 0.05.

View larger version (17K): [in a new window]   Figure 2 There is a positive, statistically significant correlation (p < 0.01) between increased heart rate and T-wave alternans level during induction of the angerlike state before (upper left panel) and during left anterior descending coronary artery occlusion (upper right panel). The slope of each line is significantly elevated above the horizontal (p < 0.0003). Beta-adrenergic blockade with metoprolol did not produce a significant decrease in the slope of the heart rate/alternans relationship (middle panels). Right atrial pacing did not increase T-wave alternans magnitude in lead II over baseline in five anesthetized canines (0.129 ± 0.026 mV x ms at spontaneous baseline rate of 107 ± 6 beats/min vs. 0.158 ± 0.023 mV x ms at 180 beats/min; slope vs. baseline, p < 0.47, lowest panel). The r2 values are: upper right panel = 0.739; upper left panel = 0.628; middle left panel = 0.764; middle right panel = 0.959; lowest panel = 0.118. These results suggest an association, but not necessarily a causal relationship, between elevated rate and T-wave alternans, as discussed in the text.

View larger version (29K): [in a new window]   Figure 3 Segments of electrocardiogram tracings with measurements of maximum T-wave alternans magnitude at baseline, during myocardial ischemia, during angerlike state and with simultaneous angerlike state and myocardial ischemia in one dog that experienced ventricular fibrillation at 42 s after provocation of angerlike response was superimposed at 1 min of coronary artery occlusion.