Myocardial ischemia is commonly diagnosed by ST-segment deviations. These deviations, however, can show a paradoxical recovery even in the face of ongoing ischemic stress. A possible mechanism for this response may be the cardio-protective effects of the autonomic nervous system (ANS) via beta--1 receptors. We assessed the role of norepinephrine (NE), a beta-1 agonist, and esmolol (ES), a beta-1 antagonist, in the recovery of ST-segment deviations during myocardial ischemia. We used an experimental model of controlled myocardial ischemia in which we simultaneously recorded electrical measurements intramurally and on the epicardial surface. The experiment consisted of three interventions: first, an ischemic, or control episode was induced without the presence of any beta-1 modulators; second, an ischemic episode was induced in which we simultaneously infused nor-epinephrine (NE), a beta-1 agonist; and third, an ischemic episode was induced in which we simultaneously infused esmolol, a beta-1 antagonist. We measured ischemia as deviations in the potentials measured at 40% of the ST-segment duration. During control intervention, 27% of epicardial electrodes showed ischemic ST-segment deviations, whereas during the interventions with NE and ES, none of the epicardial electrodes showed ischemic ST-segment deviations. Intramural electrodes revealed a different behavior with 71% of electrodes showing no ST-segment elevations during control ischemia, increasing to 79% and 82% for NE infusion and ES infusion interventions, respectively. These preliminary results suggest that recovery of intramural regions of the heart is delayed by the presence of both beta-1 agonists and antagonists even as epicardial potentials show almost complete recovery. A consequence of this epicardial recovery masks the underlying intramural ischemic tissue, resulting in a false negative marker for the presence of ischemia. Further studies must pursue different markers of ischemia that can detect intramurally localized perfusion deficits and guide suitable interventions.