BACKGROUND: Unexpected sudden death among apparently healthy individuals remains a daunting problem. We have previously shown that autonomic modulation of cardiac arrhythmias and autonomic markers, such as baroreflex sensitivity (BRS) and heart rate variability (HRV), carry predictive power after myocardial infarction. OBJECTIVE: We tested the hypothesis that a parameter combining BRS and HRV could predict risk for ventricular fibrillation (VF) during a first ischemic episode in otherwise healthy dogs. METHODS: In 43 fully instrumented dogs, BRS and frequency domain analysis of HRV were determined, as well as the occurrence (n = 10, high-risk) or absence (n = 33, low-risk) of VF during 2 minutes of myocardial ischemia superimposed on submaximal exercise. TARVA (Tonic and Reflex Vagal Activity), expressed in units, is the parameter resulting from the multiplication of BRS by HF/LF (an index of tonic vagal activity). RESULTS: High-risk dogs had markedly lower TARVA values, reflecting lower cardiac vagal activity, than low-risk animals (12 +/- 5 versus 56 +/- 43 units, P < .001). The area under the receiver-operator characteristic curve for TARVA was 0.96 (95% confidence interval 0.86 to 0.99); its optimal cutoff had a 100% sensitivity and a 88% specificity with positive and negative predictive values of 71% and 100%, respectively. CONCLUSION: Differences in cardiac autonomic activity, present in healthy dogs, allow prediction of arrhythmic risk during a first ischemic episode. Increased risk is associated with reduced vagal activity. If confirmed in humans, this finding would open the way to the identification of those apparently healthy subjects at risk for sudden cardiac death during their first episode of myocardial ischemia.