The current view regarding RSTD is not accurate. Specifically, RSTD neither necessarily occurs on the opposite side of the infarct area nor does it occur only on the opposite side of the infarct area. In present study, we noted that RSTD can occur in any lead with the infarct area as the negative pole.
Since the ECG records the potential changes of the positive and negative electrodes, the reason for the RSTD should be analyzed from the potential change of the positive and negative electrodes of the leads, respectively.
Transmembrane action potential(AP), formed by transmembrane ions, causes periodic changes in the potential inside myocardial cells, as well as reverse periodic changes in the membrane potential().  The membrane potential can be sensed by the electrode. The potential change of positive electrode recorded by the lead is the same as the change in membrane potential (), while the potential change of negative electrode is the opposite ()，which is similar to the change of intracellular potential. Under normal conditions, all myocardium changes synchronously，there is no current within the myocardium, and this fluctuation of the extracellular potential is not shown on the ECG. When myocardial injury occurs, the action potential (AP) is weakened, the AP of the normal myocardium cannot be offset by the AP of the injured myocardium, and ST segment changes appear. The ST segment of the lead with the injured area as a positive electrode is elevated, while the ST segment of the lead with the injured area as a negative electrode is depressed.
The relationship between the magnitude of ST-segment elevation and reciprocal ST-segment depression is unclear . We found for the first time that the degree of ST-segment depression in limb leads can be calculated from the degree of ST-segment elevation.
The negative electrode of the standard limb leads is a single limb electrode, whereas the negative electrode of the three aV limb leads is the average value of the two limb electrodes, and this must be calculated.
When the amplitude of the action potential (AAP) of one limb electrode decreased, the degree of ST segment depressions in the standard limb lead with the infarct area as the negative pole were equal to the degree of ST segment elevation in the lead with the infarct area as the positive pole, while the degree of ST segment depressions in the aV lead were only half of that in the standard limb lead. Figure 1 is an ECG of a patient with acute anterolateral wall STEMI, the ST segment of lead I elevated by 0.1mV, indicated the amplitude of the action potential (AAP) of left arm electrode reduced 0.1mV(assessed from ECG), the left arm electrode is the negative electrode of lead III, half the negative electrode of the lead aVF , so the ST segment depressed 0.1mV in lead III and 0.05mV in the lead aVF.
When two limb electrodes were affected by myocardial infarction, the electrode recording the normal myocardium should be determined first. Figure 3 shows an ECG of a patient with inferior myocardial infarction and right ventricular myocardial infarction, the normal myocardium was recorded by the left arm electrode. The ST segment of lead III elevated by 0.7 mV indicates that the leg electrode decreased by 0.7 mV. The ST segment of lead II elevated by 0.5 mV indicates that the AAP of the leg electrode was 0.5 mV less than that of the right arm electrode，so the AAP of the right arm electrode was 0.2 mV less than that of the left arm electrode. The negative electrode of aVL is the average value of the right arm and leg electrode, AAP decreased 0.45 mV [(0.7 mV + 0.2 mV) / 2], and the ST segment decreased by 0.45 mV. The negative electrode of aVR is the average value of the left arm and leg electrode, AAP decreased 0.35 mV[(0+ 0.7 mV)/2], ST segment decreased by 0.15 mV(0.35 mV -0.2 mV), and lead I decreased by 0.2 mV.
According to the current view, anterior wall myocardial infarction should have RSTD in the posterior wall , but this is not the case (Figure 3). This is because the negative pole of all leads is in the limb leads, and part of the anterior wall myocardial infarction may not involve the limb leads. In this study, there were 10 patients with anterior myocardial infarction who showed no RSTD in any leads. There were 25 patients with anterior wall myocardial infarction combined with left lateral wall myocardial infarction and 5 patients with inferior wall myocardial infarction. The range of the inferior wall or left lateral wall myocardial infarction in patients with anterior wall myocardial infarction is generally small, with slight ST segment elevation in limb leads and most patients do not have RSTD in the posterior leads.
Currently the depression in leads V1and V2 is considered the reciprocal of and similar in meaning to the ST-segment elevation in the V8 and V9. However, depression in leads V1and V2 is also seen in right ventricular myocardial infarction.  The negative electrode of precordial leads is the Wilson’s Central Terminal, which is the average value of three limb electrodes. Myocardial infarcts with ST segment elevation in limb leads may cause RSTD in precordial leads. The depression in leads V1 and V2 is the RSTD of ST elevation in the inferior leads, not the posterior or right ventricular leads. The ST segment depression of V1 was rare in right ventricular myocardial infarction, because right ventricular action potential recorded by V1 was decreased too. ST segment was mostly normal or elevated and only a few showed depression.
The reason for the absence of RSTD in the precordial leads in inferior infarction was that the precordial electrode was close to the infarct area and the AAP was also reduced. Another reason was that the AAP of the inferior myocardium was slightly weakened, which had no obvious effect on the potential of the negative electrode of the precordial lead. Among the 13 patients with inferior myocardial infarction without ST segment depression in the anterior leads, ST segment elevation in the inferior leads was 0.1 mV in five patients, 0.1–0.2 mV in seven patients, and 0.4 mV in one patient(combined with extensive anterior wall ST segment elevation).
The link between RSTD and clinical outcomes has been extensively studied since long , and majority of the previous research suggests that RSTD is associated with clinical prognosis.[9-14] ST segment depression occurs in some patients due to multivessel lesions, and the prognosis of these patients is poor. However, even in patients without multivessel disease, RSTD may be associated with poor prognosis. RSTD is related to the degree of ST segment elevation—the more the ST segment elevation in limb leads, the greater the risk of ST segment depression in chest leads. Furthermore, the degree of RSTD between limb leads is directly related to the degree of ST segment elevation in the infarct area.
Limitations: It is difficult to obtain patients’ local myocardial action potential clinically. Thus, we can only speculate about the mechanism in terms of the characteristics of ST segment change, but the mechanism we have proposed completely conforms to the characteristics of ST segment change, making it the most reasonable and scientific mechanism so far. It is expected that experiments on animals could obtain the local action potential of the myocardium and directly verify the proposed mechanism.
In summary, the mechanism of RSTD in acute myocardial infarction maybe that the AP of negative electrode of the lead was weakened or disappeared, and the AP of positive electrode could not be completely offset, resulting in ST segment depression.