Myocardial infarction why st elevation

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Sign In. Advanced Search. Search Menu. Article Navigation. Close mobile search navigation Article Navigation. Volume Article Contents Abstract. Introduction: definition of the disease. Imaging of myocardial infarction. Targeting pathophysiological pathways in myocardial infarction: new therapeutic strategies. Pathophysiology of ST-segment elevation myocardial infarction: novel mechanisms and treatments. Oxford Academic. Federico Carbone. Thomas H. Revision received:.

Select Format Select format. Permissions Icon Permissions. Abstract Despite major advances in mechanical and pharmacological reperfusion strategies to improve acute myocardial infarction MI injury, substantial mortality, morbidity, and socioeconomic burden still exists. Acute myocardial infarction , Pathophysiology , Treatment.

Open in new tab. Figure 1. Open in new tab Download slide. Figure 2. Figure 3. Table 2 Experimental studies investigating new therapeutic strategies for treatments of myocardial infarction. Additional findings were reduction of oxidative stress and neutrophil infiltration. Hausenloy et al. As additional findings, treatment inhibited neutrophil recruitment within infarcted heart and serum levels of CXCL2. Figure 4.

Table 3 Clinical trials investigating new therapeutic strategies for treatments of myocardial infarction. Study design number of patients. Treatment follow-up. Stone et al. The electrophysiological properties were reproduced using the cell model proposed by Stewart et al.

The propagation of excitation was formulated with the bidomain model, and was solved using the parallel multilevel technique, which we previously developed and validated [ 31 ]. Briefly, in the heart domain. The following conditions were imposed on the boundaries between the domains:.

The reference point for the extracellular potential was placed at the bottom right of the torso model. The parameter values used are listed in Table 1. Anoxia caused by ischemia induces a variety of metabolic changes including acidosis, ATP depletion, and hyperkalemia.

The influences of these changes on ionic currents were modeled as follows Fig. Thus, we used the same values for the intracellular and extracellular spaces. Jones et al. Maximum conductance of the late sodium current was scaled transmurally by 1. We found two reports supporting the susceptibility of epicardial cells to ischemia compared with endocardial cells.

In that study, the 8. We shifted the half-activation voltage of epicardial cells to model this heterogeneity. We modeled a case in which the proximal portion of the left anterior descending artery, just after the bifurcation of the left circumflex artery, was blocked Fig. We studied the three types of ischemia in this region:. To examine the mechanisms underlying transmural ischemia, acute subendocardial ischemia was simulated for comparison.

Considering the ischemia-resistant nature of the Purkinje network [ 2 ], the electrophysiological properties of the Purkinje system were not modified. For acute transmural ischemia, the ischemic condition was applied transmurally to the anteroseptal region indicated in Fig.

Because the detailed time course of metabolic changes in the clinical settings was unavailable, we repeated the simulations with multiple combinations of ATP concentrations [ATP]; range, 10—0. Because of the lack of experimental data, the pH was only set at 6. Furthermore, in this case the Purkinje system was made intact.

For transmural ischemia in the chronic phase, we simulated the old myocardial infarction by eliminating the cellular function in the ischemic region. The concentrations of the major ions, [ATP], and pH after cycles of stimulation of epicardial, M, and endocardial cells under normal conditions are summarized in Table 2. Using the final results of the cell simulations as the initial condition, we then performed the heart simulation for five beats.

In all simulations, the ECG waveforms from the fourth and fifth beats were superimposable, indicating that the system was in a quasi-steady state. In all simulations, the heart was paced at 1 Hz by applying a stimulus to the root of the His—Purkinje system. All program codes were written in-house and validated in our previous studies [ 19 , 20 , 22 , 23 ]. The electrophysiology of the heart under normal conditions and subendocardial ischemia were compared Fig.

Under normal conditions, the action potential duration differed between the endocardial, M, and epicardial cells because of the differences in potassium IKr and IKs and calcium ICaL currents. The ATP-sensitive potassium current was completely inhibited transmurally Fig. Ventricular activation is shown by the time-lapse images Fig. The short axis views at the mid-ventricular level clearly indicate that the membrane depolarization of the myocytes propagates from the endocardial surface to the epicardial side Fig.

The extracellular potential distributions in the heart domain were reflected to the body surface potential Fig. Electrophysiology under normal condition and subendocardial ischemia. Numbers indicate the time after the onset of excitation in ms. RV, right ventricle; LV, left ventricle. Electrical bilayers and their solid angles at the overlying electrodes are shown in the schematics right column. RV: right ventricle; LV: left ventricle. This, in turn, produced a positive potential recorded by a precordial electrode during diastole Fig.

During systole, when the entire wall was excited, the potential gradient was reversed and the precordial electrode recorded a slightly negative voltage Fig. However, according to the convention in ECG recording, which sets the TQ-segment at zero, the ST segment is pushed further downwards to the negative side.

Accordingly, ST depressions were observed in the precordial leads overlying the ischemic region Fig. Under conditions clustered in the upper right blue , ECG morphology was largely similar to the normal pattern black bold rectangle , although the amplitude of the T wave increased at 1 mM [ATP], and then decreased with further reductions in [ATP].

The pattern of horizontal ST elevation often described in textbooks appeared under severe hyperkalemia and ATP depletion light brown. In the dark brown region, we observed ventricular arrhythmias.

ECGs with similar morphologies are grouped with different colors mild: light blue; moderate: green; severe: light brown; arrhythmia: dark brown. Conditions were selected from a for normal black rectangle , mild ischemia blue rectangle , moderate ischemia green rectangle , and severe ischemia red rectangle.

To elucidate the mechanisms underlying these ECG changes, we sampled and compared the three conditions marked by blue, green, and red rectangles Fig. Various waveforms were observed on the lead ECGs during the three increasing severities of transmural ischemia and in the chronic phase, representing the course of myocardial infarction Fig.

The cellular-level events underlying these ECG changes are summarized in Fig. Under the mild ischemic condition, selective activation of the IK ATP and downregulation of INa in the epicardium shortened the action potential duration of this region. As the severity of ischemia was increased moderate ischemia , a further inhibition of INa suppressed the action potential in the epicardium. INa also started to decline in the M and endocardial cells, and with the resultant depression in ICaL the amplitude and duration of the action potentials of these cells were reduced.

Under the severe ischemic condition, the action potentials were suppressed transmurally. In the chronic phase, the electrophysiological activities of the ischemic region were eliminated, and only the extracellular space was present transmurally.

Mechanisms of ST—T changes under ischemic conditions. During chronic ischemia, cellular activities were completely abolished. In each panel, data from the endocardial region are shown by a black line, the mid-myocardial region by a red line, and the epicardial region by a blue line. The electrical bilayers and their solid angles at the overlying electrodes are shown in the schematic third row.

The bottom panels show the ECGs V3 lead under each condition. Numbers at the bottom indicate the time after the onset of ventricular activation in milliseconds. To further elucidate how these cellular events were translated into ECG changes, we examined the potential distributions in the intracellular and extracellular spaces of the ventricular wall Fig. Because we applied the same [K] o determinant of resting membrane potentials transmurally, only the systolic phase was examined.

Under mild ischemia, an electrical bilayer, which appeared in the extracellular space during the late systole, caused broad-based, tall T waves mimicking the so-called hyper-acute T waves on the electrode overlying the ischemic region Additional file 3 : Video S3.

Moderate ischemia selectively suppressed the action potential of the epicardial layer intracellular space , thus creating an electrical bilayer with a large magnitude and an opposite polarity to that observed during subendocardial ischemia Fig. The resulting prominent ST elevation resembled the tombstone morphology reported in clinical and experimental acute ischemia [ 6 ]. The further increase in severity severe ischemia suppressed the action potentials transmurally intracellular space , although the bilayers still existed at the boundaries between the ischemic and non-ischemic regions, which generated an ST elevation of a moderate magnitude Additional file 5 : Video S5.

Finally, in the case of chronic infarction, the precordial electrode measured the potential created by the posterolateral wall from inside the ventricle, with a resulting inverted ECG waveform Additional file 6 : Video S6. Arrhythmias were observed Fig. Under these conditions, excitation initiated in the normal myocardium propagated slowly in the ischemic region 20— ms; Fig.

Thus, slow conduction in the ischemic region may play a key role in the development of arrhythmias see also Additional file 7 : Video S7. Ventricular arrhythmia during transmural ischemia. The numbers indicate the time after onset in ms. Inset: schematic presentation of the reentrant circuit. Excitation transmitted from the His—Purkinje system red lines propagates rapidly in the normal myocardium green arrow , propagates slowly in the ischemic region light brown; thin blue arrow , and finally back-propagates to the His—Purkinje system.

PMJ: Purkinje—muscle junction. ST elevation is a hallmark of myocardial infarction caused by transmural ischemia. However, the ionic mechanism is less understood compared with the ST depression observed during subendocardial ischemia.

Because ST depression is caused by the ventricular gradient directed towards the epicardium, the reversed gradient has been postulated as the cause of ST elevation [ 10 , 12 ].

However, considering the favorable anatomy and physiology of epicardial tissue for coronary perfusion [ 18 ], such a situation is unlikely to occur. In the present study, using a multi-scale heart simulation, we examined whether such a gradient is possible, and if so, how it contributes to the genesis of ST elevation. We postulated that the transmural heterogeneity in the properties of sodium and ATP-sensitive potassium channels [ 4 , 8 ] would cause the transmural gradient, which would be dependent on ischemia severity.

We found that the properties of these channels can create a ventricular gradient under moderately ischemic conditions, while under severely ischemic conditions, ST elevation was observed without the transmural gradient. As summarized Fig. Therefore, the observed changes in ECG morphologies showed similarities to the clinical course of transmural ischemia. Under mild ischemia, we observed broad-based, tall T waves mimicking the so-called hyper-acute T waves, although the amplitudes were not high.

In the present study, because there were no reported experimental human data, we used the value reported by Furukawa et al. However, the actual value may differ in human ventricular tissue. Quantitative analysis of ECG requires the computation of potential distribution in the torso domain with a complex structure and a distribution of conductivity.