Michiyasu Yamaki

Significance of discordant ST alternans in ventricular fibrillation.

With the use of epicardial mapping, we investigated the electrical alternans of the ST segment during acute myocardial ischemia and studied the difference in ST alternans between dogs with resultant ventricular fibrillation and those without it. During the 7-minute occlusion of the left anterior descending coronary artery below its first diagonal branch, 60 epicardial unipolar electrograms were recorded simultaneously at 1-minute intervals by a computerized mapping system. ST alternans was found in the eight dogs we observed. The amplitude of ST alternans (difference in the ST segment elevation of two consecutive electrograms) was greater in dogs with ventricular fibrillation (n = 4) than in those without it (n = 4) (3.92 +/- 1.24 versus 0.58 +/- 0.49 mV, p less than 0.05). Three of the four dogs with ventricular fibrillation demonstrated discordant ST alternans (i.e., adjacent leads were out of phase). Results from the present study indicate that an increased amplitude and discordance of ST alternans during acute myocardial ischemia are related to ventricular fibrillation and act as indicators of time and spatial unevenness of ventricular repolarization.

Role of ATP-sensitive K+ channel on ECG ST segment elevation during a bout of myocardial ischemia. A study on epicardial mapping in dogs.

BackgroundATP-sensitive K+ channels are activated when the myocardium becomes ischemic. However, the role of the ATP-sensitive K+ current in the emergence of ECG ST changes during ischemia remained unclarified. Methods and ResultsThe left anterior descending coronary artery (LAD) was cannulated and perfused with arterial blood from the carotid artery through a bypass tube in 8 anesthetized, open-chest dogs. An array of 60 unipolar electrodes mounted on a sock was used to record epicardial electrograms of the whole heart. Pinacidil (10 μg kg-1 min-1), an ATP-sensitive K+ channel opener, was infused into the bypass tube for 2 minutes, and the electrograms were recorded before and after the infusion. The elevation of the ST segment and the increase of QRST area were observed spatially over the LAD-perfused region. At the electrode showing the largest ST segment elevation, the activation recovery interval, an index of action potential duration, was shortened from 202±9 to 111±18 milliseconds (P<.001). These electrographic changes were similar to those noted in 2-minute coronary occlusion (n=8). The extent of ST segment elevation during coronary occlusion was attenuated after the intravenous pretreatment with glibenclamide (0.3 mg/kg), a blocker of the KATP channel (n=5) ConclusionsThe findings of this study suggest that the activation of ATP-sensitive K+ channels during a bout of acute myocardial ischemia plays an important role in the emergence of ECG ST elevation.

Discordant S-T alternans contributes to formation of reentry: a possible mechanism of reperfusion arrhythmia

Although a relationship between S-T alternans and life-threatening arrhythmia has been recognized, the mechanism is poorly understood. We examine the role of S-T alternans in the occurrence of ventricular fibrillation (VF) after reperfusion. The left anterior descending coronary artery was occluded for 20 min and then abruptly reperfused in 12 intravenously anesthetized open-chest dogs. Sixty unipolar epicardial electrograms were recorded during the control state, at the end of occlusion, and after reperfusion. The largest magnitude of S-T alternans among 60 leads was defined as the maximum S-T alternans. Isochronal maps of activation time in paced beat and spontaneous ventricular premature contractions (VPC) were analyzed. After reperfusion, VF ensued in six dogs. The maximum S-T alternans augmented progressively with time after reperfusion until VF occurred. In three dogs with VF, when activation of VPC resulted in conduction block and formed reentry, VF ensued. The conduction block was located between sites of discordant S-T alternans (S-T alternans at adjacent leads was out of phase). These data indicate that discordant S-T alternans relates to VF by facilitating the formation of a reentrant circuit.Although a relationship between S-T alternans and life-threatening arrhythmia has been recognized, the mechanism is poorly understood. We examine the role of S-T alternans in the occurrence of ventricular fibrillation (VF) after reperfusion. The left anterior descending coronary artery was occluded for 20 min and then abruptly reperfused in 12 intravenously anesthetized open-chest dogs. Sixty unipolar epicardial electrograms were recorded during the control state, at the end of occlusion, and after reperfusion. The largest magnitude of S-T alternans among 60 leads was defined as the maximum S-T alternans. Isochronal maps of activation time in paced beat and spontaneous ventricular premature contractions (VPC) were analyzed. After reperfusion, VF ensued in six dogs. The maximum S-T alternans augmented progressively with time after reperfusion until VF occurred. In three dogs with VF, when activation of VPC resulted in conduction block and formed reentry, VF ensued. The conduction block was located between sites of discordant S-T alternans (S-T alternans at adjacent leads was out of phase). These data indicate that discordant S-T alternans relates to VF by facilitating the formation of a reentrant circuit.

Glibenclamide attenuates peaked T wave in early phase of myocardial ischemia

OBJECTIVES ECG peaked T wave appears during the early phase of myocardial ischemia, but the underlying mechanisms remain unknown. The purpose of this study was to elucidate the role of ATP-sensitive K+ channel (KATP) in this ECG change. METHODS In 12 anesthetized, open-chest dogs, the sinus node was crushed and the right atrium was paced at a cycle length of 400 ms. The left anterior descending coronary artery was abruptly occluded for 60 s before (control) and 15 min after an intravenous infusion of vehicle (n = 6) or glibenclamide (1 mg/kg, n = 6), a blocker of KATP. Forty-eight epicardial electrograms were simultaneously recorded from the anterior surface of the left ventricle. The potentials at 40, 80 and 120 ms from the J point were measured, and these points corresponded to the early, middle and late phases of the T wave, respectively. RESULTS During the control occlusion, T wave increased time-dependently and the maximal T-wave change was noted at the end of 60 s of coronary occlusion. The extents of T-wave elevation at the early, mid and late T phases were 5.5 +/- 0.5, 7.3 +/- 0.8 and 11.7 +/- 1.8 mV, respectively, and these T-wave elevations were significantly reduced by 33 +/- 21%, 59 +/- 12% and 63 +/- 13%, respectively, after the pretreatment with glibenclamide but not with its vehicle. The % reductions of mid and late T by glibenclamide were significantly larger than that of early T wave (P < 0.05). CONCLUSIONS An abrupt coronary occlusion accompanied peaked T wave as an early ECG wave change. As the extent of this T-wave elevation was attenuated by glibenclamide, the ischemia-induced alteration of ventricular repolarization can partly (60%) be explained by the modification of KATP activation.

Prediction of functional recovery in acute myocardial infarction: Comparison between sestamibi reverse redistribution and sestamibi/BMIPP mismatch

BackgroundIt has been known that Tc 99m sestamibi/iodine 123 betamethyliodophenylpentadecanoic (123I-BMIPP) (sestamibi/BMIPP) mismatch is an indicator of viable myocardium in acute myocardial infarction (AMI). We have reported that reverse redistribution of sestamibi in AMI indicates the patency of infarct-related artery and a preserved left ventricular function in the chronic stage. In this study we investigated the relationship between reverse redistribution of sestamibi and sestamibi/BMIPP mismatch in patients with AMI.MethodsTwenty-three patients with AMI who received direct percutaneous transluminal coronary angioplasty underwent both BMIPP and sestamibi SPECT within 2 weeks after onset. Sestamibi images were obtained 1 hour (early) and 3 hours (delayed) after injection of sestamibi. BMIPP imaging was carried out 30 minutes after injection. The left ventricle was divided into 17 segments, and regional myocardial uptakes of the tracers in each segment were scored from 0 (normal) to 3 (no activity). A reverse redistribution pattern was defined as an increase of ≽1 in the regional score at the delayed images. More reduced BMIPP uptake than sestamibi uptake in each segment was determined as sestamibi/BMIPP mismatch. Contrast left ventriculography was performed soon after revascularization and repeated 1 month later.ResultsOf 15 patients with sestamibi reverse redistribution, sestamibi/BMIPP mismatch was observed in 14 patients (93%), whereas mismatch was seen in only one of seven patients (14%) without reverse redistribution (p<0.01). In patients with sestamibi reverse redistribution, regional scores of BMIPP agreed with those of early and delayed images of sestamibi in 51 segments (46%) and in 92 segments (83%), respectively. In the chronic stage, both regional wall motion and left ventricular ejection fraction improved in patients with sestamibi reverse redistribution (wall motion score: 6.7±2.4 vs 2.7±2.1, p<0.01; ejection fraction: 56%±7% vs 64% ±8%, p<0.01), but not in those without reverse redistribution.ConclusionBoth reverse redistribution of sestamibi and sestamibi/BMIPP mismatch reflect the recovery of left ventricular function and thus imply myocardial viability in AMI. Because the presence of reverse redistribution of sestamibi agreed with that of sestamibi/BMIPP mismatch, additional BMIPP images can be replaced by the delayed images after a single injection of sestamibi.

Body surface distributions of ST segment changes after exercise in effort angina pectoris without myocardial infarction.

To investigate the sites of exercise-induced ST segment changes on the body surface in effort angina pectoris without myocardial infarction, we performed 87-lead ECG mapping in 61 patients before and 1.5 and 5 minutes after treadmill exercise. ST segment depression most often occurred in the left anterior chest leads and ST segment elevation developed mainly in the right upper chest leads. There was a good correlation between the number of lead points that showed ST segment depression (nSTd) and the number of those that showed ST segment elevation (nSTe) 1.5 minutes after exercise (r = 0.92). From 1.5 to 5 minutes after exercise, changes in nSTd for individual patients correlated well with changes in nSTe (r = 0.89). It was suggested that the ST segment elevation observed in this study directly reflected the subendocardial ischemia of the left ventricle. In patients with one-vessel disease (n = 32), there was wide overlap in the sites of ST segment changes among patients with left anterior descending artery disease (n = 19), those with left circumflex artery disease (n = 6), and those with right coronary artery disease (n = 7). These findings should lead to a better understanding of exercise-induced ST segment changes for the diagnosis of coronary artery disease.

Intracoronary Flecainide Induces ST Alternans and Reentrant Arrhythmia on Intact Canine Heart A Role of 4-Aminopyridine–Sensitive Current

BACKGROUND The electrical alternans shown on an ST segment, ST alternans, is known as one of the most important predictors of ventricular fibrillation (VF). It has also been reported that sodium channel inhibition changes action potential configuration, especially on the repolarization phase. Thus, the sodium channel blocker may produce ST alternans and trigger reentrant arrhythmia. METHODS AND RESULTS A sodium channel blocker (disopyramide, lidocaine, or flecainide) was infused selectively into the left anterior descending coronary artery in anesthetized, open-chest dogs. Sixty unipolar electrograms were simultaneously recorded from the entire cardiac surface of the heart. The amplitude of ST alternans (STa) was determined as the difference in the ST-segment magnitude between 2 consecutive electrograms. We accepted the greatest STa among 60 leads for evaluation. High-dose flecainide (100 microg. kg-1. min-1) increased STa and evoked a spontaneous VF. The STa in high-dose flecainide loading (8.7+/-3.4 mV; mean+/-SEM) was significantly greater than that in disopyramide or lidocaine (0. 9+/-0.4 and 0.8+/-0.2 mV, P<0.05). Treatment of 4-aminopyridine (4-AP) suppressed the increase in STa and the occurrence of VF evoked by flecainide, while E4031 or verapamil did not inhibit those. CONCLUSIONS Flecainide caused the ST alternans that was closely correlated to the occurrence of VF. Because the ST alternans was suppressed by 4-AP treatment, a 4-AP-sensitive current such as Ito or Isus may play an important role on this phenomenon.

Non-invasive detection of coronary artery disease by body surface electrocardiographic mapping after dipyridamole infusion†

Electrocardiographic changes after dipyridamole infusion (0.568 mg/kg/4 min) were studied in 41 patients with coronary artery disease and compared with those after submaximal treadmill exercise by use of the body surface mapping technique. Patients were divided into three groups; 19 patients without myocardial infarction (non-MI group), 14 with anterior infarction (ANT-MI) and eight with inferior infarction (INF-MI). Eighty-seven unipolar electrocardiograms (ECGs) distributed over the entire thoracic surface were simultaneously recorded. After dipyridamole, ischemic ST-segment depression (0.05 mV or more) was observed in 84% of the non-MI group, 29% of the ANT-MI group, 63% of the INF-MI group and 61% of the total population. Exercise-induced ST depression was observed in 84% of the non-MI group, 43% of the ANT-MI group, 38% of the INF-MI group and 61% of the total. For individual patients, there were no obvious differences between the body surface distribution of ST depression in both tests. The increase in pressure rate product after dipyridamole was significantly less than that during the treadmill exercise. The data suggest that the dipyridamole-induced myocardial ischemia is caused by the inhomogenous distribution of myocardial blood flow. We conclude that the dipyridamole ECG test is as useful as the exercise ECG test for the assessment of coronary artery disease.

Improved diagnostic performance on the severity of left ventricular hypertrophy with body surface mapping.

To improve the diagnostic usefulness of electrocardiography (ECG) in determining the severity of left ventricular hypertrophy (LVH) with body surface mapping, 87 unipolar ECGs were recorded from 57 patients with left ventricular (LV) concentric hypertrophy and 30 with LV dilatation. Body surface ECG features due to LVH were evaluated by increase of QRS voltage and delayed local activation. We measured for each lead R voltage, net area of QRS (AQRS), ventricular activation time (VAT), and departure index (DI) of AQRS and VAT (DI = mean/SD). From these measurements, seven parameters were calculated for each patient: Rmax, the maximal R wave voltage; AQRSmax, the maximal AQRS; AQRS-Dmax, the maximal AQRS DI; AQRS-Darea, the area size where DIs of AQRS are more than 2; VATmax, the maximal VAT; VAT-Dmax, the maximal VAT DI; and VAT-Darea, the area size where DIs of VAT are more than 2. Among these parameters, the most effective for diagnosis of LVH were selected by stepwise multiple regression analysis. In the concentric hypertrophy group, the combination of VAT-Darea and Rmax was determined to be the best for estimating wall thickness. The regression equation determined from them correlated well to wall thickness (r = 0.73). In the LV dilatation hypertrophy group, only AQRSmax was selected for estimating LV dilatation. A good correlation between AQRSmax and LV internal dimension was observed (r = 0.73). With the body surface distribution of VAT prolongation, septal hypertrophy was separated from the other LVH. These were superior to the conventional method of 12-lead ECGs. ECG diagnosis of LVH severity improved by incorporating a mapping study. Also, prolongation of VAT and increase in QRS voltage were shown to be important when determining the severity of LVH.

Relation between recovery sequence estimated from body surface potentials and T wave shape in patients with negative T waves and normal subjects.

BackgroundAdvances in analytical methods of the epicardial electrical potentials allowed us to demonstrate spatial distributions of local recovery. Because local recovery will be reflected in events on body surface ECG mapping, abnormalities in recovery sequence that may be responsible for the origin of negative T waves can be detected from body surface potentials. Methods and ResultsEighty-seven unipolar ECGs were recorded simultaneously from the entire thorax in patients having negative T waves on left anterior precordial leads and in normal subjects. These included 40 patients with anterior myocardial infarction (MI), 21 patients with left ventricular hypertrophy (LVH), and 44 male volunteers. We measured T., time, defined as the instant of maximal first derivative of the T wave as the index of local recovery (Wyatts method). Parameters related to T wave potentials were positive T wave amplitude, negative T wave amplitude, and T integral. Significant correlations were observed between the TMAX time and each of the T wave potentials. The T wave potentials were dependent on TMAX times. In the anterior MI, the late Tma times were located on the upper left anterior chest and early T.a. times on the lower right lateral chest. In the LVH, the area showing a delayed recovery was displaced in a left downward direction compared with anterior MI. ConclusionsBody surface TMAX time distributions clearly separate two negative T wave groups, i.e., anterior MI and LVH. Appearance of the negative T waves correlates well with the presence of the area with delayed TMAX time on the spatial distribution.