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

OBJECTIVES The main goal of this study was to determine whether induction of an angerlike state can result in significant levels of T-wave alternans, a marker of electrical instability, in the normal and ischemic heart. BACKGROUND Outbursts of anger have been implicated in the occurrence of myocardial infarction and sudden cardiac death, but the pathophysiologic mechanisms remain unknown. METHODS A standardized behavioral challenge of eliciting an angerlike state was conducted before and during a 3-min period of coronary artery occlusion in six canines. RESULTS Precordial T-wave alternans increased from 0.04 ± 0.02 at baseline to 1.40 ± 0.32 mV × ms (p < 0.05) during the angerlike response. When the angerlike state and myocardial ischemia were superimposed, the augmentation in T-wave alternans magnitude (to 3.27 ± 0.61 mV × ms, p < 0.05) exceeded their additive effects, increasing by 130% over the angerlike state alone (p < 0.05) and by 390% over occlusion alone (p < 0.05). Adrenergic influences were reduced by the beta1-adrenergic receptor blocking agent metoprolol (1.5 mg/kg, intravenous), which diminished T-wave alternans magnitude (p < 0.0004 for all) during the angerlike response (from 1.40 ± 0.32 to 0.80 ± 0.17 mV × ms) and during the combined intervention (from 3.27 ± 0.61 to 1.23 ± 0.13 mV × ms). In five additional normal anesthetized canines, atrial pacing at 180 beats/min did not increase T-wave alternans magnitude monitored from lead II electrocardiogram. CONCLUSIONS Provocation of an angerlike state results in T-wave alternans in the normal heart and potentiates the magnitude of ischemia-induced T-wave alternans. Elevation in heart rate during arousal does not appear to be the main factor in the development of alternans in the normal heart but may be an important component during myocardial ischemia. Enhanced adrenergic activity appears to mediate the effects in both the normal and ischemic hearts. T-wave alternans may constitute a useful electrophysiologic measure for clinical use in conjunction with behavioral stress testing or ambulatory monitoring.