Osamu Okazaki

Comparative simulation of excitation and body surface electrocardiogram with isotropic and anisotropic computer heart models

Comparative simulations between isotropic and anisotropic computer heart models were conducted to study the effects of myocardial anisotropy on the excitation process of the heart and on body surface electrocardiogram. The isotropic heart model includes atria, ventricles, and a special conduction system, and is electrophysiologically specified by parameters relative to action potential, conduction velocity, automaticity, and pacing. The anisotropic heart model was created by incorporating rotating fiber directions into the ventricles of the isotropic heart model. The orientation of the myocardial fibers in the ventricles of the model was gradually rotated counterclockwise from the epicardial layer to the endocardial layer for a total rotation of 90/spl deg/. The anisotropy of conduction velocity and intracellular electric conductivity was included in the simulation. Comparative simulations of the normal heart, LBBB, and RBBB showed no significant differences between the two models in the excitation processes of the whole heart or in the body surface electrocardiograms. However, it was easier to induce ventricular fibrillation in the anisotropic model than in the isotropic model. The comparative simulation is useful for investigating the effects of myocardial anisotropy at the whole heart level and for evaluating limitations of the isotropic heart model.<<ETX>>

Functional role of coronary collaterals with exercise in infarct-related myocardium

We evaluated the regional myocardial blood flow in collateral dependent infarct-related areas to examine the functional role of coronary collaterals. Regional myocardial blood flow was measured by positron emission tomography with 13N-ammonia at rest and during low-grade exercise (bicycle ergometer fixed at 25 W for 6.5 min). The study was performed in 24 subjects, consisting of 19 patients with prior myocardial infarction, and five normal individuals. Regional myocardial blood flow was calculated using the radioactivity in myocardial tissue measured by positron emission tomography and the radioactivity in arterial blood. Concerning the infarct related area, the exercise caused myocardial blood flow to decrease by 18.4% (P < 0.01) in the collateral-dependent areas (n = 8) of angiographically positive collaterals, and to increase by 14.4% (P = not significant) in the areas (n = 10) of negative collaterals. Four patients in whom the myocardial blood flow in all walls, including the normal areas, decreased with exercise were excluded from this evaluation. Myocardial blood flow in collateral-dependent infarct-related areas appeared to decrease transiently by low-grade exercise. Our results suggest that collaterals increase the incidence of exercise-induced ischemia, but may protect the infarct related but viable myocardium from necrosis.

Relation Between Exercise-Induced Myocardial Ischemia as Assessed by Nitrogen-1 3 Ammonia Positron Emission Tomography and QT Interval Behavior in Patients With Right Bundle Branch Block

Exercise-induced myocardial ischemia is difficult to detect with ST-T changes in patients with right bundle branch block (RBBB). We sought to predict exercise-induced myocardial ischemia with QT interval behavior during exercise in patients with RBBB. Twenty-two patients with angiographically proven coronary artery disease and RBBB and 9 healthy volunteers underwent nitrogen-13 ammonia positron emission tomography with bicycle ergometer exercise at a fixed workload of 25 W. Regional myocardial blood flow (RMBF) and electrocardiographic changes were measured both at rest and after 5 minutes of exercise. The QT interval was measured from the onset of the QRS complex to the offset of the T wave in lead V5. The deltaQT and deltaRMBF, which indicated values after 5 minutes of exercise minus values at rest, were negatively correlated (r = -0.74, p <0.001). Exercise-induced shortening of the QT interval (422 +/- 27 to 381 +/- 38 ms, p = 0.0020) was observed in 15 patients (group 1) and no change or prolongation (411 +/- 45 to 420 +/- 37 ms, p = NS) was observed in 7 patients (group 2). Multivessel disease was significantly more frequent but collateral circulation was significantly less in group 2 than in group 1 (p <0.01, p <0.05, respectively). Cardiac output at rest was significantly lower in groups 1 and 2 than in healthy volunteers (4.52 +/- 0.83 and 4.51 +/- 0.84 vs 6.20 +/- 0.83 L/min; p = 0.0014, p = 0.0003). Although RMBF at rest did not differ significantly among groups 1 and 2 and healthy volunteers (0.63 +/- 0.20 vs 0.69 +/- 0.13 and vs 0.77 +/- 0.14 ml/min/g), RMBF after 5 minutes of exercise was significantly lower in group 2 than in group 1 and healthy volunteers (0.78 +/- 0.11 vs 0.96 +/- 0.20 and vs 1.20 +/- 0.18 ml/min/g; p = 0.0289, p <0.0001). The number of regions of critical coronary artery disease was significantly greater in group 2 than in group 1 (4.0 +/- 1.2 vs 2.1 +/- 1.3, p = 0.0039). Our results suggest that the absence of QT interval shortening during exercise may indicate severe myocardial ischemia induced by exercise in patients with RBBB and coronary artery disease.

Correlation between exercise-induced ischemic ST-segment depression and myocardial blood flow quantified by positron emission tomography

BACKGROUND Ischemic ST-segment depression (horizontal or downsloping) is the most common manifestation of exercise-induced myocardial ischemia. The mechanisms responsible for these types of ST-segment depression are largely unknown. We investigated the relation of these 2 types of exercise-induced ST-segment depression to changes in regional myocardial blood flow (RMBF) by using exercise positron emission tomography (PET). METHODS AND RESULTS The RMBF was measured with nitrogen-13 ammonia PET both at rest and during low-level supine bicycle exercise in 27 patients with angiographically proven coronary artery disease and in 6 healthy volunteers. ST-segment depression was measured from the isoelectric PR segment 80 ms after the J point. Exercise-induced horizontal ST-segment depression > or =0.1 mV was observed in 9 patients and downsloping depression > or =0.1 mV was observed in 18 patients. Multivessel disease was more frequent and areas of exercise-induced ischemia were larger in patients with downsloping depression than in patients with horizontal depression (P < .02, P < .05). In patients with horizontal ST-segment depression, RMBF in ischemic areas and in surrounding areas increased by a similar amount (31%+/-29% and 32%+/-16%) with exercise. In patients with downsloping ST-segment depression, RMBF was unchanged or decreased in ischemic areas (10%+/-24%) but increased in surrounding areas (46%+/-27%) with exercise. In healthy volunteers, RMBF increased in all areas (56%+/-30%) with exercise. CONCLUSIONS Compared with horizontal changes in ST-segment morphology, downsloping changes may better indicate severe ischemia and greater differences in the increase of blood flow with exercise in the ischemic myocardium and in the surrounding areas.

Inducing and suppressing ventricular fibrillation: A simulation study with three-dimensional heart model and experimental data

Ventricular fibrillation was simulated using three-dimensional heart model incorporating anatomic and electrophysiologic details. A parameter relating restitution of premature action potential durations to coupling interval of stimulation was defined and incorporated into the heart model to simulate the cell dynamics. Conduction delay during relative refractory period was also taken into account. During sinus pacing extra-stimuli were applied to the left ventricular epicardium of the heart model. As long as up to 8 seconds of the sequential excitation process of the heart model and the resultant electrocardiograms on a torso model were computed. Ventricular fibrillation was successfully induced and suppressed by employing experimental data obtained from dogs before and during the infusion of antiarrhythmic drugs.

Exercise-induced ST-segment changes permit prediction of improvement in left ventricular ischemic dysfunction after revascularization: Evaluation with positron emission tomographic measurements of regional myocardial blood flow and cardiac output☆

BackgroundPrediction of the recovery of left ventricular (LV) ischemic dysfunction after revascularization is important in patients with coronary artery disease (CAD). We investigated whether the improvement in LV ischemic dysfunction after revascularization could be predicted preoperatively by exercise-induced ST-segment changes.Methods and ResultsRegional myocardial blood flow (RMBF) and cardiac output were measured with nitrogen 13-ammonia positron emission tomography at rest and during low-level exercise in 28 patients with angiographically proven CAD before and after successful revascularization and in 9 normal subjects. Before revascularization, exercise-induced upsloping ST-segment depression <1 mm 80 msec after the J-point was observed in 11 patients (group 1), horizontal depression of 1 to 1.5 mm was observed in 0 patients (group 2), and downsloping depression ≥1.5 mm was observed in 8 patients (group 3). The number of regions of critical CAD was greater in group 3 than in groups 1 and 2 (3.6±1.4 vs 1.6±0.7 and 2.2±1.1, p<0.001, p<0.02). Increase of RMBF in regions of critical CAD with exercise was lower in group 3 than in groups 1 and 2 (0.15±0.01 vs 0.22±0.01 and 0.18±0.02 ml/min per gram, p<0.0001, p <0.01). After revascularization, RMBF in regions of critical CAD both at rest and during exercise improved in groups 1 (0.49±0.15 to 0.60±0.18, 0.70±0.26 to 0.86±0.33 ml/min per gram, both p<0.05) and 2 (0.50±0.15 to 0.62±0.19, 0.67±0.26 to 0.89±0.31 ml/min per gram, both p<0.02), but was unchanged in group 3 (0.47±0.09 to 0.47±0.15, 0.62±0.17 to 0.64±0.23 ml/min per gram, both p=NS). Cardiac output at rest improved in groups 1 (4.98±0.43 to 5.35±0.50 L/min, p<0.02) and 2 (5.08±0.52 to 5.53±0.28 L/min, p<0.02), but was unchanged in group 3 (4.76±0.48 to 4.88±0.82 L/min, p=NS).ConclusionsOur results suggest that marked downsloping ST-segment depression induced by preoperative low-level exercise may predict a lack of improvement in LV ischemic dysfunction after revascularization.

A simulation study of torsade de pointes with m cells

Recent studies have reported the relation between Torsade de Pointes (TdP) and midmyocardial (M) cell function associated with long QT syndrome. To investigate this relation, we conducted a simulation study with a three-dimensional (3D) heart model incorporating M cells in the anterolateral areas of the model. Parameters of premature cycle-length dependent shortening of action potential duration (APD) and conduction velocity for the M cells were adjusted to induce tachyarrhythmias of TdP type. Under a basic pacing cycle length of 1,000 msec at the sinus node, four successive premature beats of 160-ms interval were generated 300 ms after the first sinus pacing. Setting lower conduction velocity and longer APD to M cells induced sustained TdP-like tachyarrhythmia resembling ECG findings. TdP could not be induced without the presence of M cells. This study suggests that TdP might be caused by reentry around M cells and dispersive refractory areas due to prolonged APD and slow conduction velocity.

Comparison of body surface potential maps simulated with isotropic and anisotropic computer heart models

Simulated body surface potential maps (SBSPM) with isotropic and anisotropic heart models were compared to investigate the effect of myocardial anisotropy on body surface electrocardiograms at a whole heart level. Rotative fiber orientations of total 90 degrees was incorporated into an isotropic heart model. The anisotropy of conduction velocity and intracellular electric conductivity was included in the simulation. SBSPM based on epicardial, intramural, and endocardial stimulation show high correlation with fiber orientations. On the other hand, the anisotropy cannot be distinguished from the SBSPM in the simulation of normal heart model.

Paradoxical QRST integral changes with ventricular repolarization dispersion

Body surface QRST integral (QRSTI) maps have been shown theoretically to reflect disparity of intrinsic repolarization properties and have been experimentally linked to increased arrhythmia susceptibility. Paradoxically, a lower magnitude of QRSTI in patients with heart disease and at risk for arrhythmias has been reported. We hypothesized that this paradoxical reduction in QRST magnitude is a consequence of increased heterogeneity of repolarization gradients in normal hearts. We generated QRSTI using a previously published heart model to compare QRSTI for aligned and random repolarization gradients. The heart model consisted of 50,000 cubic units in an anatomically correct arrangement that included parameters to simulate anisotropic conduction and inhomogeneous distribution of refractoriness. Body surface potential maps (BSPMs) were generated on a torso surface assuming a homogeneous torso and using the boundary element method for normal alignment of repolarization gradients and spatially reassigned repolarization values that randomized repolarization directions. QT duration was measured by the subtraction of Q onset time from T offset time on the BSPM. T offset was defined as the last potential to be detected at intervals of 3 ms that was above the threshold of 0.1 mV during recovery. The time of T offset showed a consistent tendency to shift to the left posterior and to split. When slow conduction velocities were assigned, BSPMs showed delayed propagation and multiple extrema. QRSTI showed systematic magnitude decrease with increasing randomness of repolarization gradient direction. Ventricular fibrillation (VF) could be induced by successive extrastimuli under the conditions of over 70% deviation and slow conduction of 0.5 m/s for the longitudinal direction. In conclusion, a possible explanation for the paradoxical reduction in QRSTI in the presence of constant repolarization disparity is the change in alignment of repolarization gradients.

Derive right precordial leads at higher intercostal spaces from 12-lead system for diagnosis of Brugada syndrome

Recording the right procordial leads at higher intercostal spaces (ICS) can raise the sensitivity of the diagnosis on Brugada syndrome using ECG. However, the directive measurement of the right precordial leads at the higher ICSs is tedious and impractical. In this paper, we proposed a derivation method based on the information redundancy in the 12-lead system to study the possibility of deriving the right precordial leads at the higher ICSs from the commonly used Mason-Likar 12-lead ECGs. Through the evaluation based on the simulated Brugada-type ECGs and recorded ECGs from BS subjects, we found that the BS characteristic J wave and coved type ST elevation in the right precordial leads at the higher ICSs could be satisfyingly derived from the 12-lead ECGs. It is concluded that the derived precordial leads at the higher ICSs may serve as an assistant diagnosis tool to unmask Brugada syndrome.