Search

Si-rich ytterbium silicide was fabricated by through an arc-melting technique for applying use as a bond coat material in an environmental barrier coating system. Evaluation of its potential was accomplished through oxidation tests in dry air and an inert atmosphere. The experimental results showed that the changes in weight and morphologies of ytterbium silicide observed after the tests depended on the oxygen partial pressure. Extensive oxidation and weight gain occurred after oxidation in air. In order to apply this material for hot structures, improvement of the oxidation resistance is needed.

Ytterbium (Yb)- and silicon (Si)-rich ytterbium silicides (Yb5Si3, and Yb3Si5) were successfully fabricated by arc-melting and heat treatment. The degradation behavior of both silicides was evaluated by means of oxidation tests under three different conditions: Air, air-H2O, and steam. The results showed that the degradation of these Yb-silicides in air was accelerated relative to that in air–H2O and in steam. Although Yb3Si5 formed an un-oxidized region in air–H2O and in steam, a complex phase transformation occurred as a result of the decrease in the amount of Yb in Yb3Si5, caused by exposure to heat, while the liquid phase evolved below the melting point of Si. The liquid phases did not form upon exposure of Yb5Si3 to heat, whereas Yb5Si3 was more oxidized and the amount of SiO2 formed during heat exposure in air-H2O and steam is higher than Yb3Si5.

A ternary alloy with an Yb-Gd-Si composition was designed using thermodynamic calculation software. The ternary alloy with two different steady-state phases (Yb:Gd:Si = 25:18:57 and 19:23:58 at%) was successfully fabricated using arc melting. Oxidation tests were carried out at 1200 °C for 1, 2, 4, and 8 h in air. Thermogravimetric and microstructural analyses indicated that weight gain during oxidation at 1200 °C was suppressed compared with that for the Yb–Si alloy (Yb3Si5) owing to the formation of complex oxides in the Yb2O3–Gd2O3–SiO2 system. In addition, the phase stability of Yb-Gd-Si was higher than that of Yb3Si5 because the growth of a eutectic phase in Yb-Gd-Si during oxidation was prevented compared with Yb3Si5. The addition of Gd in Yb–Si alloy was effective in improving phase stability and oxidation behavior.

Background The specific changes in the gating kinetics of the sodium current (INa) responsible for its phenotype have remained to be elucidated. In the present study the effect of changes in the gating kinetics of INa on early repolarization (ER) and initiation of phase 2 reentry (P2R) were evaluated in a theoretical epicardial ventricular fiber model. Methods and Results Miyoshi-ICaL was incorporated into the modified Luo-Rudy dynamic (LRd) model. Dispersion at Ito-density was set within a theoretical fiber composed of serially arranged epicardial cells with gap junctions. The following changes in INa kinetics were made: (1) a -10 mV shift in steady-state inactivation, (2) a +10 mV shift in steady-state activation curve, (3) a small inactivation time constant (DEC); P2R and ER were observed. A conduction disturbance within the fiber was simulated and only when the INa-density was decreased did DEC, especially, show a marked increase in the likelihood of causing ER and P2R. Conduction disturbance significantly increased the likelihood causing ER or P2R. Conclusions In this one-dimension model with Ito-density dispersion, DEC-INa precipitates INa-blocker inducible ER. This suggests that the characteristic ST-segment elevation in the Brugada syndrome with SCN5A mutation can be interpreted in part by DEC-INa. Concomitant conduction disturbance may be required to cause P2R at physiological Ito density. (Circ J 2005; 69: 567 - 575)

Repetitive monomorphic ventricular tachycardia with a morphology of inferior axis and left bundle branch block pattern in patients without structural heart disease commonly originates from the right ventricular outflow tract. We report the case of a 22-year-old man with an incessant, monomorphic ventricular tachycardia with a similar morphology originating from the left coronary cusp, which was confirmed by perfect pace mapping, local ventricular activation preceding the onset of QRS by 25 mse, and eliminated by a single delivery of low-energy (11 W) radiofrequency currents.

We tested whether acute pressure overloading of the left ventricle (LV) had spatially different effects on repolarization, thereby causing arrhythmias. The effects of gadolinium (Gd3+), a nonspecific blocker of stretch-activated channels were also examined. In anesthetized dogs, 5 s clamping of the ascending aorta (AC), separated by 5-min intervals, was repeated while monophasic action potentials (MAPs) were recorded from the LV endocardium and epicardium. Gd3+ was injected into the left atrium before the second (500 μmol) and third AC (2500 μmol) (n=10). In a separate group (n=7), the effects of Gd3+ in the presence of verapamil were examined. Epicardial MAP durations at 50% and 90% repolarization (APD50; APD90) shortened in response to LV pressure rise and elongation of the segment length induced by the first AC, whereas endocardial MAP durations remained unchanged. Thus, the difference in APD50 and APD90 increased. Consistent with these changes, premature ventricular contractions (PVCs) developed. Gd3+ had no effect on baseline MAP durations, however it prevented an AC-induced increase in the difference by suppressing epicardial MAP shortening. Gd3+ also reduced PVCs in a dose-dependent manner at plasma concentrations of 1-4 μmol/L. The effects were also evident after administration of verapamil. Thus, gadolinium suppressed an increase in the spatial dispersion of repolarization and arrhythmias via a mechanism of action different from that of verapamil. (Jpn Circ J 1999; 63: 296 - 302)

心筋虚血によるKATPチャネル開口が不整脈に及ぼす影響を検証する目的で, 左冠動脈前下行枝の5分間閉塞を反復する麻酔開胸犬モデルにおいてKATPチャネル作動薬の効果を検討した.KATPチャネル遮断薬の前投与は虚血心筋のMAP短縮を有意に抑制したが虚血時ならびに再灌流時のVT/VFの発生率を増力口させ, 逆に開口薬はMAP短縮を促進しVT/VFの発生率を低下させた.MAP持続時間の心拍毎の変動 (alternans) が開口薬により軽減され, 遮断薬により増強する場合を認めた.また, MAPの短縮に一致したERPの短縮は認めず, ERPへの開口薬の影響も軽微であった.以上の結果から, KATPチャネル開口は虚血性ならびに再灌流不整脈に対して催不整脈的ではなく抑制的に作用することが示唆された.β・α受容体遮断薬, 伸展活性化チャネル遮断薬もVT/VFの発生率を低下させたが, KATPチャネル開口薬とβ遮断薬はMAP短縮を抑制せずに抗不整脈作用を示した点で, 心筋保護との両立の観点から理想的な薬物治療と思われた.

The relationship between the occurrence of ventricular fibrillation (VF) and repolarization abnormalities of the ischemic and reperfused myocardium is poorly understood. The present study examined the temporal relationship between ischemia- and reperfusion-induced changes in monophasic action potential (MAP) configurations and the occurrence of VF, and assessed the effects of repetition of ischemia. The left anterior descending coronary artery of 32 anesthetized dogs was occluded twice for 5 min, 30 min apart, during constant atrial pacing while recording MAPs from the epicardial ischemic zone. During the first occlusion, shortening of the MAP duration at 90% repolarization (APD90) and an increase in MAP alternans, defined as the maximal difference in APD90 between 2 consecutive beats, were observed. Afterdepolarizations also occurred transiently in 35% of the animals during occlusion and in 29% upon reperfusion. VF occurred in 28% (9/32 of the dogs) during the first sequence, and the incidence was higher in the subgroups with maximal alternans ≥20 ms (p

A 24-year-old woman had experienced frequent attacks of orthodromic AV reciprocating tachycardia. The polarity of the delta waves suggested a right anterior or anterolateral accessory pathway. After ablation at the tricuspid annulus was unsuccessful, earliest retrograde atrial activation was recorded on the floor of the right atrial appendage, 2 cm above the tricuspid ring. Application of radiofrequency energy at this site abolished accessory pathway conduction. This unusual accessory pathway, located between the floor of the right atrial appendage and the right ventricle, was amenable to radiofrequency catheter ablation from within the right atrial appendage.

冠閉塞-再灌流時の不整脈発生に及ぼす自律神経系の影響とそのメカニズムを遠心性交感神経刺激 (SS) ・自律神経作動薬を用いて検討した.pentobarbital麻酔開胸犬において左冠動脈前下行枝の5分間閉塞-再灌流操作を30分間隔で反復, 2回目を対照としてそれ以降に行った操作の影響を評価した.冠閉塞-再灌流時の心室頻拍・心室細動 (VT・VF) の発生率はいすれもSSにより増加した.MAPにおける後脱分極の記録頻度もSSにより増加した.一方, 虚血心筋の拡張期興奮閾値の上昇はSSにより抑制された.虚血領域心表面47点の再分極時間 (QTI) は冠閉塞後短縮し, 興奮到達は遅延した.β遮断後にはこれらの変化が抑制され, 不均一性 (47点の標準偏差) の増加およびVT・VFが抑制される場合を認めた.α刺激時には再びQTIが短縮し, 不整脈の発生率が増加した.phentolamineは逆にMAPの短縮を抑制した.交感神経系は虚血性不整脈および再灌流不整脈の発生率を増加させた.そのメ力ニズムとして, 虚血心筋の再分極時間の短縮の促進と不均一性の増大, 後脱分極発生の増加が推測された.

異方性伝導時の局所QT間隔の変化を心表面マッピング法を用いて検討した.麻酔開胸犬の左室心表面47点から単極および双極電位を記録した.前者からQT, 後者から局所興奮到達時間 (AT) を計測し, QTからATを引いたものを局所QT間隔 (QTI) と定義し, 再分極時間の指標とした.6点同時刺激により心筋線維走行に平行 (L) および垂直 (T) 方向の興奮波を作成した.興奮の等時線図から異方性伝導が確認された領域でのQTIは, 心房刺激時 (161.0±14msec) に比しL, T伝導時 (217.2±15, 203.4±18msec) とも有意に延長し, L伝導時に最長であった (n=9, p

Objectives. We examined the modulatory effects of autonomic nervous system and antiarrhythmic drugs on the ST segment in patients with Brugada syndrome to gain an insight into the mechanism of ST segment elevation. Background. Right bundle branch block, ST segment elevation and ventricular tachyarrhythmias define a distinct clinical and electrocardiographic (ECG) syndrome (Brugada syndrome). However, the mechanism of ST segment elevation and the causes of this syndrome are unknown. Methods. The study included four patients in whom structural heart or coronary artery disease was excluded by noninvasive and invasive tests. High take-off ST segment elevation of either the coved or saddle-back type in precordial leads V 1 , V 2 and V 3 was seen in all patients. Three patients experienced recurrent episodes of syncope or aborted sudden cardiac death, and the remaining patient had palpitation. Autonomic receptor stimulation and blockade and intravenous administration of antiarrhythmic drugs were performed during sinus rhythm while the 12-lead ECG was recorded. Metaiodobenzylguanidine (MIBG) scanning and Holter monitoring were also performed. Results. Beta-adrenoceptor stimulation by intravenous isoproterenol consistently reduced (≥0.1 mV) ST segment elevation at or 80 ms after the J point in all four patients. Selective alphaadrenoceptor stimulation by intravenous norepinephrine in the presence of propranolol or by intravenous methoxamine consistently augmented, whereas alpha-adrenoceptor blockade reduced, ST segment elevation in three patients. Intracoronary acetylcholine or intravenous edrophonium or neostigmine augmented ST segment elevation without inducing coronary spasm in three of four patients. Class IA antiarrhythmic drugs also consistently augmented (three patients), whereas class IB drugs had no effect on (two patients) ST segment elevation. No abnormality was found on MIBG imaging or heart rate variability in three patients, suggesting that autonomic dysfunction is not a primary disease process. Class IA drugs had no effect on ST segment in three control patients, suggesting that the ST segment elevation seen in patients with Brugada syndrome in response to the drugs is not a nonspecific response. Conclusions. ST segment elevation in patients with Brugada syndrome was augmented by selective stimulation of alphaadrenoceptors or muscarinic receptors or by class IA drugs but was mitigated by beta-adrenoceptor stimulation or alphaadrenoceptor blockade. These responses might be explained by postulating the presence of an area of early repolarization or a local “depolarized” area in the ventricle causing ST segment elevation in this syndrome. Because only a small number of patients were studied, these possibilities need further evaluation.

刺激部位による心室筋局所再分極時間の相違とそのメ力ニズムを単相性活動電位 (MAP) を用いて検討した.麻酔開胸犬の心房・左室心外膜面に一定周期の電気刺激を連続的に3-5秒間ずつ行った.MAPの90%再分極時間 (APD90) および同記録部の局所心筋長 (拡張末期長: EDL) を超音波変位計により計測した.MAP近傍 (1Gm以内) の心室刺激時APD90は心房刺激時に比して有意に延長したが (205±7.2vs.191±7.5msec, n=10, p

We report a patient with Brugada syndrome who developed sustained monomorphic ventricular tachycardia (SMVT). The patient was a 29-year-old man who experienced recurrent episodes of palpitation and syncope after drinking alcohol. Electrocardiogram showed right bundle branch block and ST-segment elevation in precordial leads V1-3 without Q-Tc prolongation. Organic heart disease and coronary artery disease were excluded by noninvasive and invasive tests. Ventricular fibrillation was induced by the application of a single extra-stimulus to the right ventricular outflow tract. During isoproterenol infusion, SMVT of left bundle branch block morphology (240/min) was induced by the application of a single extrastimulus to the right ventricular apex. SMVT also developed spontaneously. Pace mapping disclosed that SMVT originated at the free wall of the right ventricular outflow tract. Head-up tilt test and an alcohol provocation test both induced similar SMVT that was associated with hypotension and near syncope. SMVT was not terminated by intravenous administration of lidocaine, procainamide or adenosine triphosphate (10 mg), but was terminated by propranolol. Thus, a beta-adrenoceptor-mediated mechanism appears to play an important role in SMVT in this patient. The site of origin of SMVT might be closely related to the lesion that causes ST-segment elevation.

We tested 5-hydroxydecanoate (5-HD), a specific blocker of ATP-sensitive potassium channels (IK.ATP), to determine if mitigates electrophysiologic changes produced by regional myocardial ischemia in vivo. A sequence of 5-minute occlusion of the distal LAD and 30-minute reperfusion was repeated while recording the monophasic action potential (MAP) and bipolar electrogram (EG) from the epicardial center of the ischemic myocardium in anesthetized dogs. 5-HD (30 mg/kg, i.v.) or glibenclamide (0.15 or 0.3 mg/kg, i.v.) was administered before the third occlusion, and the data were compared to the second occlusion data. 5-HD did not affect baseline MAP duration at 90% and 50% repolarization (APD90, APD50) before LAD occlusion but suppressed occlusion-induced shortening of APD90 (16 +/- 2% during the second occlusion vs. 5 +/- 3% during the third occlusion, n = 8, p0.01) and APD50 (16 +/- 3% vs. 10 +/- 3%, n = 8, p0.05). Pretreatment with glibenclamide also suppressed occlusion-induced MAP shortening and eliminated an additional effect of 5-HD (n = 3). 5-HD did not affect the occlusion-induced increase in duration and activation time of EG. 5-HD, as well as glibenclamide, suppressed regional ischemia-induced MAP shortening, probably by blocking activation of IK.ATP, without affecting conduction delay. These differential effects of 5-HD on repolarization and conduction during the early phase of regional ischemia might have the potential to suppress reentrant ventricular arrhythmias.

局所心筋虚血時の単相性活動電位持続時間 (APD) 変化へのATP感受性Kチャネル (KATP) 活性化の関与を心筋内層 (endo) と外層 (epi) において比較検討した.麻酔開胸犬で心房ペーシングにより心拍数を一定に保ちながら, 左冠動脈前下行枝の5分間閉塞を30分間隔で反復した.3回目冠閉塞前にKATPの阻害薬である5-hydroxydeoanoate (30mg/kg; 5-HD) を静脈内に投与し2回目冠閉塞時 (対照) のデータと比較した.対照冠閉塞時, 虚血領域心筋のAPDは両層において短縮し, 再灌流により前値に復した.初期2分間のepiの短縮率および短縮速度はendoに比し有意に大で, 両層間のAPDの差は増大した.5-HD投与によるAPDの変化はなかったが, 3回目冠閉塞後のAPDの短縮は有意に抑制され, 両層間での短縮速度の差は消失した.冠閉塞時の心筋血流量の低下はepiに比しendoで大であった.以上より, 虚血早期のAPD短縮にKATPの活性化が関与し, 活性化閾値は虚血程度の軽いepiでより低いことが示唆された.

Radiofrequency catheter ablation (RFCA) for inappropriate sinus tachycardia (IST) is associated with a high recurrence rate and sometimes requires pacemaker implantation, especially after extensive ablation. We report a patient with drug-refractory IST who was successfully treated by selective RFCA to the 2 earliest activation sites. During tachycardia, the earliest atrial activation preceded the surface P wave by 50 ms or more, whereas it was only 27 ms for the rest of the right atrium after ablation. Our patient had the longest activation period during tachycardia among the reported patients. In IST patients, a longer activation time at the site of the earliest atrial activation may imply that the abnormality is confined to a small area within the sinus node and may predict the efficacy of selective RFCA.

The effects of the activation sequence on ventricular repolarization and its spatial gradient were examined in anesthetized open-chest dogs. Unipolar and bipolar electrograms were recorded from 47 epicardial sites on the anterior left ventricular wall using a mapping electrode. The local QT interval (QT) and the activation time (AT) at each site were measured on the unipolar and bipolar electrograms, respectively. The QT index (QTI) was defined as the QT minus AT interval, and was used as a measure of local repolarization. QTI was longer at each site during propagation that was longitudinal (L) (219+/-21 ms) than during propagation transverse (T) (202+/-22 ms, p

Nicorandil is a clinically used nitrovasodilator that has a property as an opener of ATP-sensitive potassium (KATP) channels in vitro. We examined whether nicorandil at a clinically used dose augmented regional ischemia-induced monophasic action potential (MAP) shortening and increase in extracellular potassium concentration ([K+]o), and how it affected arrhythmia occurrence. Five-minute occlusion of a distal site of the left anterior descending coronary artery (LAD) was repeated at 30-min intervals in anesthetized open-chest dogs while recording MAP or measuring [K+]o with a potassium-sensitive valinomycin electrode from the epicardial center of the ischemic myocardium. Nicorandil (0.2-0.5 mg/kg) was administered intravenously (i.v.) 5 min before the third occlusion, and the data were compared with those during the second occlusion (control). During the second occlusion, MAP duration at 90% repolarization (APD90) shortened (mean rate for 5 min, 13 +/- 3%, n = 11) and [K+]o increased from 3.7 +/- 0.1 to 6.2 +/- 0.8 mM at 5 min (n = 12). These changes were reversed < or = 3 min after reperfusion. Before the third occlusion, baseline APD90 and [K+]o were not altered by nicorandil; however, the extent of occlusion-induced shortening of APD90 (25 +/- 4%) and [K+]o increase (7.8 +/- 1.6 mM) was augmented by the pretreatment. The drug effect was attenuated by a concomitant pretreatment with 5-hydroxydecanoate, a specific blocker of KATP channels (n = 2). The prevalence of ventricular fibrillation (VF) during occlusion/reperfusion sequence was reduced after nicorandil (1 of 25 vs. 5 of 25) without de novo VF. These results suggest that nicorandil at a clinical dose facilitates regional ischemia-induced activation of myocardial KATP channels without causing serious proarrhythmia. Such a property might help protect the myocardium against ischemia/reperfusion damage.

There is some controversy regarding the mechanisms of an upward shift in the left ventricular diastolic pressure-volume curve during ischemia. The effects of handgrip exercise on the pressure-volume curve were examined in 21 patients with coronary artery disease and in 6 control subjects. Pressure-volume curves were constructed from digitized left ventricular pressure and volume derived from biplane left ventriculogram. Diastolic pressure-volume curve shifted upward in 12 patients with coronary artery disease during handgrip exercise (Group 1), but not in the other 9 patients who were similarly afflicted (Group 2). The upward shift did not occur in any control subject. No difference was observed in rate-pressure product gain during exercise. In Group 1, left ventricular end-diastolic pressure increased (p less than 0.01) and ejection fraction was reduced (p less than 0.01), although it did not change in Group 2. In Group 1, the time constant was prolonged (p less than 0.01) with no change in the coefficient for elastic modulus. In Group 2, these parameters remained unchanged. Group 1 was accompanied by more extensive asynergy than Group 2. Thus, isometric handgrip exercise resulted in an upward shift in the diastolic pressure-volume curve in patients with coronary artery disease. Incomplete relaxation and/or the viscoelastic properties of the left ventricle associated with ischemia could be responsible for this phenomenon.

The purpose of this study was to examine the effects of acute ischaemia superimposed on an electrophysiologically stable, small myocardial infarction, and to determine the mechanisms of induced ventricular arrhythmias, using a canine infarction model. Ten dogs without inducible ventricular tachycardia or fibrillation on the 7th day post-myocardial infarction (Group 1) and 14 control dogs (Group 2) were subjected to 30 min acute ischaemia by occlusion of the proximal left anterior descending artery. The areas of infarcted myocardium ranged from 1.0 to 20.4% (mean 8.9, SD 7.7) of total left ventricular weight. Ventricular arrhythmias were inducible by programmed electrical stimulation in eight of 10 dogs (80%) after acute ischaemia, but in only one of 14 control dogs (7%) (p less than 0.005). In seven of eight Group 1 dogs, epicardial mapping showed that ventricular arrhythmias did not originate from the epicardial region. In one dog, in which there was simultaneous epicardial and endocardial mapping, an endocardial electrogram from the boundary area between infarcted and acutely ischaemic zones recorded continuous fragmented activity. It was thus suggested that re-entry in a relatively isolated endocardial site could be attributed to the induction of ventricular tachyarrhythmias, and that the electrical instability could be significantly enhanced during acute ischaemia when underlying myocardial infarction was present.

A patient with malignant lymphoma who developed congestive heart failure, conduction disturbances and myocardial infarction is presented. Two-dimensional echocardiography revealed marked thickening of the left ventricular wall, where the gallium scan correspondingly showed an abnormal accumulation. Irradiation to the mediastinum resulted in a dramatic decrease in ventricular wall thickness and disappearance of the gallium accumulation. Postmortem examination confirmed previous lymphomatous involvement of the myocardium. Combined techniques, including echocardiography and gallium scan, can be valuable for noninvasive detection and follow-up of myocardial involvement in patients with malignant lymphoma.

The effects of carteolol, a β-blocking agent, on the incidence of ventricular arrhythmias and ventricular automaticity were studied in a canine acute myocardial infarction model. Carteolol (10 μ g/kg) was given intravenously 5∼ 30 minutes before balloon occlusion of the left anterior descending coronary artery in anesthetized, closed chest dogs (Group I). The total incidence of ventricular arrhythmias during the first 30 minutes of coronary occlusion was 91% (10/11) in group I, similar to control dogs without pretreatment of carteolol (Group II; 92%, 12/13, NS).However, ventricular fibrillation or sustained ventricular tachycardia was not observed in Group I, compared to 2 cases in the Group II dogs.Ventricular escape interval (VET), used as an index of ventricular automaticity, progressively shortened in the periods between 1 and 4 hours post-occlusion in both groups. However, the mean value of VET at 4 hours after coronary occlusion in Group I was significantly longer than.that of the Group II dogs (1549 ± 1259 msec vs 610 ± 224 msec, P

Myocardial protective effects of intracoronary administration of relatively small doses of propranolol were examined and compared with systemic administration in 20 open-chest dogs. In group 1 (n = 6) rate-pressure-product (R X P) did not change during 5-minute left anterior descending artery (LAD) perfusion with deoxygenated Krebs-Henseleit solutions (KHS). However, R X P decreased by the same degree in group 2 (n = 7), which received perfusion with KHS containing 0.4 or 0.8 mg/dl of propranolol, and in group 3 (n = 7) given LAD perfusion with original KHS and systemic administration of 0.02 to 0.04 mg/kg of propranolol. Total administered doses of propranolol were the same for groups 2 and 3. Transmural biopsy after 5 minutes of perfusion revealed less severe metabolic deterioration of hypoxic myocardium in group 2 when compared with that in group 1, as evidenced by higher ATP (adenosine triphosphate) (2.81 +/- 0.35 versus 2.23 +/- 0.45 mumol/g, p less than 0.05) and lower lactate content (5.62 +/- 1.44 versus 9.01 +/- 2.62 mumol/g, p less than 0.05). On the other hand, significant metabolic preservation was not noted in group 3. Sequential changes in regional myocardial contraction did not differ among the three groups. In conclusion, intracoronary administration of propranolol showed myocardial protective effects that were not mediated by the changes in hemodynamics and myocardial contraction.

Changes in left ventricular (LV) diastolic indices after left ventriculography (LVG) with iopamidol or urografin were studied in 42 subjects. Increase in heart rate and decrease in LV systolic pressure were more significant with urografin than with iopamidol (p less than 0.05 to 0.001). LV end-diastolic pressure was elevated more with urografin than with iopamidol (p less than 0.005 to 0.05) 1 to 3 minutes after LVG. LV peak negative dP/dt decreased significantly with urografin immediately (10 to 15 seconds, -511 and 30 seconds, -376 mm Hg/sec; p less than 0.0005 to 0.02), but with iopamidol it did not decrease significantly after LVG. Time constant, T, was elongated with iopamidol (10 to 15 seconds, +13 and 30 seconds, +6 msec; p less than 0.0005), but this elongation was significantly less than urografin (10 to 15 seconds, +34; 30 seconds, +25; 1 minute, +15; and 2 minutes, +10 msec; p less than 0.05 to 0.0005). We conclude that iopamidol disturbed LV diastolic function to a lesser degree than did urografin.

The myocardial protective effect of nicorandil, N-(2-hydroxyethyl) nicotinamide nitrate ester, against hypoxia was examined in comparison with that of nitroglycerin in 22 open chest dogs. The regional ventricular myocardium was perfused for 5 min with a hypoxic solution in 8 dogs (Group 1), with a hypoxic solution containing 0.5 or 2.5 mg/dl of nicorandil in 7 dogs (Group 2) and with a hypoxic solution containing 0.5 mg/dl of nitroglycerin in 7 dogs (Group 3). In Group 2, the ATP content of the hypoxic myocardium was 3.14 +/- 0.37 mumol/g, which was less than that in the uninvolved myocardium (4.31 +/- 0.57 mumol/g) but significantly higher than those of the hypoxic myocardium in Groups 1 and 3 (2.09 +/- 0.45 and 2.39 +/- 0.33 mumol/g, respectively). The lactate content of the hypoxic myocardium in Group 2 (5.05 +/- 1.13 mumol/g) was less than those of the hypoxic myocardium in Groups 1 and 3 (8.77 +/- 2.34 and 8.98 +/- 2.08 mumol/g, respectively). This protective effect was not caused by the hemodynamic changes. In contrast, nitroglycerin did not show any protective effects on the hypoxic myocardium.

The difference between the right (RV) and the left ventricle during progressive pressure loading is that the RV changes to cylindrical form without change in its enddiastolic pressure (EDP). We investigated this particular phase experimentally and clinically. In experimental animal studies (dogs), the gradual construction of the main pulmonary artery (PA) resulted in an elevation of RV systolic pressure (RVSP) without changes in RVEDP and PA flow (FPA). This was followed by an increase in RVEDP and a decrease in FPA. In this initial phase, the RV increased in its dimension from the free wall to the septum. In 155 clinical cases with RV pressure loading, the relationship between RVEDP and RVSP suggested that the RV compliance of the cases with chronic RV pressure loading was less than that with subacute loading. However, these studies did not supply the expected data on the phase we mentioned. In 2 patients with primary pulmonary hypertension who showed spontaneous remission during our observation, a decrease in RVSP without change in RVEDP occurred with a change in RV form detected by 2-dimensional echocardiography. These data suggested the existence of a phase in which the RV showed a character of plasticity during pressure loading, but direct documentation was not successful.

Bipolar myocardial electrograms and extracellular potassium concentrations were simultaneously monitored using double barrelled probes during 30 min of acute ischaemia in 15 dogs in vivo. The responsiveness of the time from the onset of the limb lead electrocardiogram to the peak deflection of the local electrogram to extracellular potassium changes was more prominent in superficial intramyocardium than in deep intramyocardium, despite similar changes in potassium concentration in both layers. The changes in electrogram duration and amplitude were related to extracellular potassium concentration both in superficial and deep intramyocardium. Immediate phase ventricular arrhythmias (within the first 10 min of acute ischaemia) were characterised by delayed activity mainly due to an increase in the time to peak of the electrogram in superficial intramyocardium. In contrast, in dogs showing delayed phase arrhythmias (within 10-30 min of acute ischaemia) delayed activity associated with pronounced changes in potassium concentration and electrogram duration and amplitude were noted in deep intramyocardium. Thus the two phasic appearances of early ischaemic ventricular arrhythmias with different origins seem to be related to the features of the conduction pathway in superficial intramyocardium and the severe local electrogram changes associated with a pronounced increase in extracellular potassium concentration in deep intramyocardium.

Regional effects of intracoronary administration of nicardipine, a dihydropyridine derivative with calcium blocking activity, were studied in 13 open-chest dogs. Hypoxic, constant-flow perfusion was done in the area supplied by the distal left anterior descending artery. The 5-min regional hypoxic perfusion did not result in significant alterations in either heart rate or aortic pressure in 6 control dogs perfused with original Krebs-Henseleit solution (KHS), which was deoxygenized by mixed gas (95%N2 and 5%CO2), and in 7 dogs perfused with nicardipine-containing (0.2 mg/dl) KHS. A transmural biopsy after 5 min of perfusion revealed a less severe metabolic deterioration in nicardipine-treated dogs than in control dogs, as indicated by a higher ATP content (2.84 +/- 0.43 vs. 2.23 +/- 0.45 mumol/g, wet weight). The sequence of regional contractile deterioration was not different between the 2 groups. In conclusion, regional nicardipine administration showed a myocardial protective effect which was not mediated by afterload reduction in the whole heart.

The effects of antiarrhythmic agents on automatic ventricular tachycardia (VT), which emerged in the early stage of acute myocardial infarction (AMI), were examined in 30 closed-chest mongrel dogs. Antiarrhythmic agents were administered intravenously when the rate of VT became almost equal to sinus rate (5.6 ± 1.4 hours). VT was slowed significantly by verapamil (0.15 or 0.3 mg/kg), diltiazem (0.2 or 0.4 mg/kg), propranolol (0.1 mg/kg) and amiodarone (5 mg/kg), but not by procainamide (20 mg/kg), lidocaine (2 or 4 mg/kg), nifedipine (0.01 mg/kg) and nicorandil (0.03 mg/kg). The number of ventricular premature complexes was reduced most effectively by verapamil. The significant suppressive effects of calcium antagonist drugs (verapamil and diltiazem) and propranolol indicate that an inward calcium current during diastole may play a critical role In the abnormal enhancement of ventricular automaticity in the early stage (4 to 8 hours) of AMI.

The changes in activation sequences in and around the epicardial reentrant circuit were analyzed during rapid pacing against ventricular tachycardia by using a canine infarction model. In 13 episodes of sustained ventricular tachycardia induced by a premature stimulation technique in eight dogs, reentry circuits were located in the superficial subepicardial myocardium in eight. Pacing stimuli were clearly demonstrated to enter the reentrant circuit in two directions: one wavefront collided with the orthodromic reentrant wavefront and the other entered prematurely into the reentrant circuit to reset the tachycardia (resetting phenomenon). With a faster pacing rate, stimuli failed to reset the tachycardia due to slower entry into the circuit despite the fact that most epicardial recording sites were activated by pacing wavefronts (concealed perpetuation). Termination of tachycardia was achieved by a local conduction block in the center of the reentrant circuit. A pacing impulse which encountered the local block was also shown to reinitiate the tachycardia using a different reentrant pathway. These different phenomena could be observed in consecutive pacing beats. These epicardial mapping data provided a direct electrophysiological basis for the mechanisms of reentrant ventricular tachycardia and the mode of its termination.

Mechanisms by which Class I drugs interrupt or facilitate reentrant ventricular tachycardia (VT) induced by programmed stimulation were analysed in dogs with 7-day-old myocardial infarction. Activation time and effective refractory period (ERP) were determined at 48 sites of survived epicardial layer within the infarction zone (IZ) and surrounding normal zone. Two mg/kg of lidocaine (L), propafenone (P) and flecainide (F) were administered intravenously. Induction of sustained VT was prevented by P in 7 of 10 cases, in 3 of 5 cases by F and in one of 8 cases by L (P vs L, p less than 0.01). Proarrhythmic effects were encountered in a case of P and 2 cases of F. Conduction velocity within the IZ was reduced by each drug to the same extent. The ERP within the IZ was prolonged by each drug, however, the mean extent of change differed significantly among the drugs (P 37% greater than F 26% greater than L 10%). In cases in which an antiarrhythmic effect was achieved, it was the result of abolition of the re-excitation at retrograde exit site of reentry circuit, which was considered to be due to prolongation of refractoriness at the site. These results suggest that prolongation of local refractoriness within the IZ is the major antiarrhythmic mechanism. The proarrhythmic effect was accompanied by an increased dispersion of local ERP as well as by a marked reduction of conduction velocity within the IZ.