In all sheep studied, we found sinus rhythm at the induction of anesthesia and at steady state. Three sheep were excluded from the study; in two sheep, the esophageal recording was too noisy to analyze after the steady state, and one sheep developed ventricular fibrillation and died immediately after occlusion of the coronary artery. The waveform of the ECG and the E-ECG activity before myocardial ischemia are shown in Figure 1.
The recording in the E-ECG showed an early, low-amplitude part and a steep (prominent), high-amplitude biphasic P component, which occurred simultaneously with the P wave in the S-ECG during sinus rhythm. The mean amplitude of the biphasic P component in the E-ECG was 1.7 +/- 0.098 mV (range 1.1-2.6 mV), and the mean duration of the P components was 0.071 +/- 0.009 s (range 0.071-0.08 s). The mean voltage of the QRS segment was 3.9 +/- 3.5 mV (range 1.9-5.1 mV), the mean duration of the QRS segment 51 +/- 28.4 ms (range 28-89 ms), the mean voltage of the T wave was 1.4 +/- 1.7 mV (range 0.4-4.3 mV), and the duration of the T wave averaged 120 +/- 32.8 ms (range 76-160 ms).
During steady state, the S-ECG showed no signs of myocardial ischemia. The E-ECG presented with homogenous ST segments, without any beat-to-beat alternans (Figure 1).
In the second minute after occlusion, 7 of the 15 (47%) sheep revealed significant ST segment changes in the S-ECG (Table 1), whereas an increase in the ST alternans in the E-ECG (Table 1) was evident in 14 of the 15 sheep (93%) within 2 min of occlusion (P < 0.01). Electrical alternans was defined as a repetitive beat-to-beat fluctuation of E-ECG amplitude within the ST segment (Figure 2). All 15 sheep displayed wall motion abnormalities and a bluish discoloration in the ischemic area in this time period.
Distinct ST segment changes in the S-ECG were seen in 13 of the 15 animals (87%) in the interval from the 3rd to the 30th min. In the same observation period, all 15 sheep presented visible ST alternans on the E-ECG (Table 1, Figure 3). In the sheep with an increase in the ST alternans in the first 2 min, repolarization showed further exponential increase in nine cases in the next 30 min after the onset of ischemia.
The central finding was that the ischemic ST alternans was visually apparent in E-ECG but not in S-ECG. Using E-ECG, there was good correlation of the measurable ischemia (Table 2) with alternans to the morphology in the ST segment (Figure 2 and Figure 3). Coronary artery occlusion resulted in significant increases in the magnitude of the dynamic beat-to-beat alternation in ST segment amplitudes in the E-ECG signal (Figure 1, Figure 2 and Figure 3). The increase in ST segment alternans in the E-ECG significantly preceded the development of ST depression/elevation in the S-ECG (P < 0.01) (Table 1). We observed the development of "notched," "bifid," "dimpled," or "cloven" ST segments displaying humps, bulges, or protuberances before or just beyond the apex or on the descending limb of the T wave, above and below the isoelectric line (Figure 3). Frequently, the T wave alternans was concentrated during the first half of the T wave.
The main goals of this study were to evaluate the experimental esophageal recording of myocardial ischemia and infarction with a specifically designed preamplifier and to assess the association between ST segment alternans and ischemia and/or infarction.
ECG lead placement is important in detecting ischemia, especially intraoperatively and during cardiac surgery. Even with V5 monitoring, changes in lead position during chest opening and closure can lead to a failure to detect ongoing myocardial ischemia . Electromagnetic current dipole theory  predicts that reducing the distance between the recording electrodes and the cardiac signal source will result in a linear improvement in detection of subtle dynamic changes in the waveform. It must be assumed that the remote dipoles of surface leads would be less effective in detecting ST segment alternans than an esophageal electrode closer to the ischemic zone .
In the literature, there is only a single report of a patient with posterior ischemia who developed ST segment elevation only in an E-ECG and not in S-ECG leads II or V5 during a coronary bypass grafting procedure , and there has been no basic research on E-ECG and acute myocardial infarction .
The concept of measurement of ST segment alternans in the E-ECG is based on the idea that visible inhomogenities from beat-to-beat and increased differences in the amplitudes of the ST segment in the E-ECG lead reflect increased inhomogeneity in myocardial repolarization, providing a tool for tracking myocardial ischemia . The differentiation of electrocardiographic repolarization abnormalities indicative of acute myocardial processes from those that are the result of depolarization (QRS) alternans has been the subject of study, debate, and speculation for many years and is beyond the scope of discussion in this paper [17-19].
The lack of reports describing ST alternans recorded via the esophagus is surprising. Initially, E-ECGs were performed using S-ECG amplifier systems. Bipolar electrodes were simply connected to the terminals of a conventional S-ECG device [6,7], regardless of the low resistance and improved conduction properties of a bipolar esophageal lead. We connected our bipolar esophageal lead to a specifically designed preamplifier to increase the sensitivity .
The bipolar E-ECG presented herein was measured from the proximal electrode to the common electrode and against the distal electrode to the common electrode. This differs from a "pseudo" bipolar S-ECG, in which both electrodes are measured against the common electrode. Additionally, in S-ECGs, the reference electrode is more distant than it is with our E-ECG. This means that the E-ECG signals present a challenge that S-ECG equipment cannot meet.
Although an alternans can occasionally be identified on clinical ECG tracings, the alternans is usually so subtle than it cannot be detected visually . The S-ECG, with its specific filter technique, encounters high skin electrical impedance, low electrical conductivity, motion artifacts, potentials generated by the skin, and electromyographic noise. The baseline in the S-ECG may be stabilized by further filtering of low-frequency signals or by high-pass filtering . In contrast, the E-ECG is not contaminated by the wide range of voltages generated by physiological and other sources. With this in mind, we constructed a preamplifier with a wide frequency range and a bipolar lead.
During steady state, we observed very homogeneous ST segment intervals in the E-ECG (Figure 1). Immediately after the onset of ischemia, sheep presented visible ST alternans on the E-ECG. Repolarization alternans increased exponentially during the next 30 minutes after the onset of ischemia (Figure 2, Figure 3). This demonstrated the high sensitivity of the E-ECG, and the waterfall diagrams display consecutively inhomogenous repolarization periods (Figure 1, Figure 2 and Figure 3). Additionally, we calculated the sum of the differences of the mean net potentials and each next beat (Table 2). It is in good accordance with a report that the greater the variability in local repolarization processes, the greater the deviation of the sum of the net areas of QRS and T from zero . We propose that this calculation can serve as an index of heterogeneity of the repolarization process. Nearing et al.  showed no alternans in the nonischemic area in a canine model, and after occlusion, marked alternans of the T-waves, in good accordance with our results. They concluded that T wave alternans is an "electrophysiological characteristic of the ischemic myocardium" [18,19].
In humans, there remains discussion as to whether the E-ECG reflects more sensitively only the electrical potential of the posterior surface of the heart because of its close anatomical location to the posterior aspect of the left ventricle. When the axis of the sheep heart is compared with that of the human heart, the axis of the sheep heart is rotated to the right, and the relations between the anterior and posterior walls of the heart to the esophagus are fairly comparable.
Epicardial ECGs recorded simultaneously from the ventricle showed T wave alternans after left anterior descending coronary artery occlusion , in good accordance with the phenomenon in the E-ECG. We did not use epicardial electrodes because of the risk of injury and artifacts on insertion. Further work could involve different esophageal placements and different sizes of the electrodes, time series analysis, and Fourier transformations. The presented E-ECG signals were clearly seen and were easy to separate from artifacts, so we did not perform frequency analysis in both depolarizations and repolarizations. Additionally, further E-ECG studies should compare T wave alternans during the first and second halves of the T wave, and the "pilot" nature of these data require validation in humans. Clinical application and evaluation of the E-ECG to detect ST segment alternans could involve assessment of intraoperative myocardial ischemia, especially during cardiac surgery.
Based on our present findings, ST segment alternans in the E-ECG obtained from a bipolar lead positioned in the esophagus provided a remarkably high degree of sensitivity for the prediction of ischemia. Thus, quantification of the magnitude ST segment alternans may provide a useful tool for assessing vulnerability in cases of ischemia and repolarization disturbances. Despite the absence of visible ST segment alternans on the S-ECG, the E-ECG reveals a clearly definable peak of repolarization alternans with myocardial ischemia. The quantification of E-ECG ST segment is a promising technique for intraoperative ischemia detection compared with currently available methods.
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