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全国107施設の運動負荷試験に関するアンケート調査により, 推定累積運動負荷試験1, 779, 352件 (マスター2階段試験951, 512件, エルゴメーター法215, 972件, トレッドミル法611, 868件) における事故について検討を行った.死亡事故6件, 入院を要する重篤事故37件であり, 検査10, 000件当たりの事故率は, 死亡0.034, 心筋梗塞発症0.129であった.死亡を含む重篤事故の基礎疾患が明らかであったのは31件であり, 内訳としては心筋梗塞13%, 不安定狭心症13%, 狭心症32%であり, 肥大型心筋症, 拡張型心筋症, 弁膜症などその他が42%であった.事故の内容 (総数40件) は, 心筋梗塞発症57.5%, 不安定狭心症12.5%, 持続性ST上昇10%, その他20%であった.事故の原因としては, 報告のあった33件の中で過度の虚血6%, 過度の負荷15%, 不安定狭心症に負荷を行った6%, その他15%であり, 原因不明が58%を占めた.過去に事故の経験の有無による運動中止基準の比較では, 運動中止心拍数および収縮期血圧が事故の経験ある施設において年齢別推定最大心拍数85%以上や収縮期血圧250mmHg以上の設定など中止基準の設定が高い傾向を認めたが, 運動中止STレベルには差を認めなかった.本邦における運動負荷試験に伴う事故の発生頻度は, 過去の諸外国の報告よりは少ない傾向であったが, 事故の原因として不安定狭心症に負荷を行った例や過剰負荷の例が認められ, 事故の防止のため負荷試験の適応と禁忌, 運動中止基準の遵守がより必要と考えられた.

We conducted a retrospective study (1981-1990) to determine whether the efficacy of intracoronary thrombolysis (ICT) could be evaluated from data obtained solely after recanalization. We investigated 55 successful ICT patients (38 with anterior and 17 with inferior myocardial infarction (MI)), and 31 control infarct patients without recanalization. The total serum creatine phosphokinase release (sigma CPK), the extent of infarction measured by T1-201 single photon emission computed tomography (total DS) and the disturbance of regional wall motion (asyn.%) were investigated as parameters for distinguishing the successful ICT and control groups. Discriminatory ability for the two groups was highest with the total DS in all patients. Only the total DS differed significantly between the two groups in patients with inferior infarction. Misidentification of control patients as successful patients was least frequent (25.5%) when using the total DS. These findings suggest that the effectiveness of ICT for acute MI may be assessed on the basis of data obtained solely after recanalization, with the total DS being particularly useful.

The electrophysiologic properties of SUN1165 and its suppressive effect on supraventricular tachycardia were assessed in 14 patients, nine with atrioventricular reentrant tachycardia (AVRT) and five with atrioventricular nodal reentrant tachycardia (AVNRT). This new agent prolonged the PR interval and QRS duration but did not alter the QT interval or the corrected QT interval. It did not alter the sinus cycle length or sinus node recovery time. The drug prolonged the AH interval, HV interval, and intraatrial conduction time but did not change the effective refractory periods of the right atrium or right ventricle. SUN1165 prevented the induction of tachycardia in six of nine patients with AVRT by a complete retrograde block of the accessory pathway and prevented AVNRT in four of five patients by a complete retrograde block of the fast atrioventricular nodal pathway as well. We conclude that SUN1165 is very effective in preventing AVRT or AVNRT. Larger studies with more patients are warranted.

The authors investigated, in vivo, the effects of four vasodilators on venous tone in dogs. Baseline venous tone was determined from the pressure: diameter relationships in the inferior vena cava (VSIVC) and femoral vein (VSFV) as measured during several seconds of occlusion of the proximal inferior vena cava. All of the slopes were nearly linear. All vasodilators were adminstered in dosages sufficient to lower blood pressure by approximately 20%; these dosages also decreased systemic vascular resistance by 15% to 30%. Isosorbide dinitrate reduced VSIVC from 7.17 ± 0.81 to 5.81 ± 0.73 mmHg/mm and VSIVC from 59.4 ± 13.5 to 37.2 ± 6.6 mmHg/mm. Neither nifedipine nor nisoldipine altered VSIVC or VSFV. However, prazosin decreased VSIVC from 13.2 ± 3.3 to 10.7 ± 2.7 mmHg/mm and VSFV from 43.5 ± 11.3 to 29.9 ± 8.8 mmHg/mm. These results suggest that isosorbide dinitrate and prazosin decrease venous tone in vivo, whereas nifedipine and nisoldipine do not.

To evaluate the clinical usefulness of Doppler-derived cardiac output and the effect of altered left ventricular function during maximal treadmill exercise, this study was performed using continuous wave (CW) Doppler technique through the suprasternal notch acoustic window. Subjects consisted of 22 patients with coronary artery disease (study 1) and 21 healthy male volunteers (study 2)

The effects of physical training on hemostatic parameters were evaluated in 56 postmyocardial infarction (MI) patients before and after one month of systematic physical training and in 30 control post-MI patients, who did not undergo such training. There were no significant changes in prothrombin time (PT) and alpha 1-antitrypsin (alpha 1AT) at the beginning and end of the study in either group. Levels of fibrinogen, Factor VIII: C (VIII:C) and von Wildebrand antigen (vWf:Ag), and activities of ATIII and plasminogen (Plg) were significantly decreased in the group with physical training (p less than 0.05), while values were unchanged in the control group. Hematocrit, platelet counts, and alpha 2-plasmin inhibitor (alpha 2PI) activities also decreased in the physical training group (p less than 0.05). In contrast, these variables increased in the control group (p less than 0.05). Activated partial thromboplastin time (aPTT) tended to be prolonged in the group with physical training, while it was shortened in the control group. In a subset of 20 patients with physical training, resting levels of plasmin-alpha 2PI complex (PIC), thrombin-antithrombin III complex (TAT), protein-C (P-C:Ag), plasminogen activator inhibitor-1 (PAI-1), VII:C, and P-C activities had significantly decreased after one month of physical training (p less than 0.05), although tissue plasminogen activator activities remained unchanged. Physical training appeared to suppress coagulability as indicated by the decrease in fibrinogen, VIII:C, vWf:Ag, VII:C, and TAT, and prolongation of aPTT. The decrease in plasminogen, t-PA:Ag, alpha 2PI, PAI-1, and PIC after physical training may result from the decreased coagulability. In conclusion, physical training appears to induce a suppression of the coagulation system in patients in the recovery phase of MI.

An active orthostatic stress test was conducted on 32 elderly patients over 65 years (elderly group) and 17 normal adults, for a comparative evaluation of their blood pressure, heart rates, and plasma catecholamine responses. In addition, 8 patients in the elderly group underwent a study of orthostatic responses with or without sublingual administration of isosorbide dinitrate (ISDN). The results of the orthostatic responses were evaluated by Schellong's method. The elderly group produced a positive reaction in one (3.1%), and a weakly positive reaction in two (6.3%), while the remaining 29 (90.6%) and all of the normal adults showed negative responses. The systolic blood pressure pattern that developed in response to rising among the elderly group was significantly different (p less than 0.001) from that of the normal adult group, but the response pattern seen in the heart rates of the former approximated that of the latter. The plasma norepinephrine concentration 10 minutes after rising increased significantly (p less than 0.001) in both the elderly and normal adult groups. This increase amounted to 1.5-fold in the elderly group and 2-fold in normal subjects, with a less prominent increase shown by the elderly. The norepinephrine levels of the elderly group were significantly higher than those of the normal adults both before and 10 minutes after rising (p less than 0.001 and p less than 0.01, respectively). In the elderly, ISDN caused a significant drop in the systolic blood pressure immediately after rising and a significant increase in the heart rate. Sublingual ISDN administration resulted in a significant increase in the norepinephrine level (p less than 0.05) in association with rising. These findings indicated that the circulatory responses to orthostatic stimuli are inappropriate as clinical data among the elderly and the administration of ISDN exaggerates this shortcoming further.

In 13 patients with an implanted dual-chamber atrioventricular (AV) demand pacemaker, left ventricular performance was elicited by pacing mode manipulation for study using gated cardiac pool scintigraphy at rest and during exercise. There was no significant difference between DDD and VVI at 70 and 90 beats/min with respect to cardiac output, peak ejection rate or peak filling rate. At 110 beats/min, the cardiac output was greater with DDD as compared to VVI. The peak filling rate was also significantly greater with DDD as compared to VVI (DDD : 3.6 vs VVI : 2.8 EDV/s, p

Sex and age differences of ventricular gradient (G) were analyzed and normal ranges were determined in normal Japanese subjects (120 men and 74 women), whose resting heart rate was within the range of 65 to 75 beats/min. Women showed a larger Z component in ÂT and a smaller Y and larger Z component in G than men. The common trend in age differences was a decrease in Y component of G in both men and women. The ranges obtained in the present study can be applied in automatic VCG analysis, in particular for the differentiation of primary and secondary ST-T changes.

To assess the prognostic value of an abnormal postexercise response in systolic blood pressure (SBP), treadmill exercise testing was performed in 217 survivors of acute myocardial infarction at an average of 9.3 weeks after infarction. During the mean follow-up period of 4 years, cardiac events were noted in 34 patients (16%), including cardiac death in 13 (6%), nonfatal reinfarction in 12 (6%), and coronary artery bypass graft surgery in nine (4%). An abnormal postexercise SBP response was defined as the ratio of SBP at 3 minutes of recovery to peak exercise SBP of 0.9 or more, on the basis of the cutoff point with the highest sensitivity and specificity to predict cardiac events. An abnormal postexercise SBP response occurred in 90 patients (42%). Patients with an abnormal postexercise SBP response had more exercise-induced myocardial ischemia. more left ventricular impairment, and more extensive coronary artery lesions than those without. Cox proportional hazards model demonstrated that the abnormal postexercise SBP response was ranked first in ability to predict cardiac death (p = 0.025, relative risk 15.41). Bypass surgery was associated with an abnormal postexercise SBP ratio (p less than 0.05). Nonfatal reinfarction could not be predicted by any clinical or exercise variables. In conclusion, an abnormal postexercise SBP response could be useful for predicting cardiac death and the need for bypass surgery after myocardial infarction. This response is probably the result of myocardial ischemia and left ventricular impairment.

The authors investigated the usefulness of the Karhunen-Loeve technique applied to body surface maps to study regional cardiac excitation. Eigenvectors were derived from the body surface potential maps of 120 healthy adults using the Karhunen-Loeve expansion theory. Then, in the maps of various types of ventricular hypertrophy, each eigenvector coefficient was calculated for a statistical comparison. The first eigenvector coefficient in early QRS and the second in mid QRS were larger in patients with asymmetrical septal hypertrophy and in patients with left ventricular hypertrophy, respectively. The third was larger in patients with right ventricular hypertrophy. In the maps of patients with previous anteroseptal myocardial infarction, the second eigenvector coefficient decreased with asynergy of the anterior to apical wall, and the first decreased with the asynergy of the interventricular septum. They conclude that some eigenvector components and coefficients at particular times in the QRS are sensitive to changes in regional cardiac excitation and that they may facilitate the detection of local excitation changes such as occur in hypertrophy or infarction.

Correlation studies were carried out between thallium-201 myocardial perfusion images and vectorcardiograms in 77 patients with myocardial infarction (48 anterior and 29 inferior infarctions) and 30 patients with hypertrophic cardiomyopathy. A quantitative method was developed; myocardial 201Tl uptake index (a relative myocardial activity to background, MUI) and myocardial 201Tl uptake ratio (a ratio of regional myocardial counts to maximal myocardial counts, MUR) were utilized to differentiate myocardial infarction from hypertrophic cardiomyopathy, and evaluate them. A fairly good agreement between left ventriculograms and myocardial perfusion images was obtained in myocardial infarction (diagnostic accuracy 95.1% in anterior and 75.6% in inferior infarction). In anterior infarction the linear relationship of r = -0.58 (p < 0.001) was obtained between asynergy index and mean anterior MUR. A highly significant correlation was observed between anterior MUR and the instantaneous 24 msec Z component (r = -0.80, p < 0.001). In inferior infarction, Qy/Ry was correlated to inferior MUR (r = -0.58, p < 0.001). In hypertrophic cardiomyopathy, four types of hypertrophic sites were classified with 201Tl images (septal, apical and anterior, apical and septal, and anterior dominant types). Azimuth angles of instantaneous 10 msec vector were directed right-anteriorly (mean 114.5 degrees) in septal hypertrophy, and left-anteriorly (mean 84.9 degrees) in apical and anterior hypertrophy. Elevation angle of maximal T vector in apical hypertrophy was deviated superiorly (mean 102.6 degrees). There was a good correlation (r = 0.60, p < 0.001) between the magnitude of spatial maximal QRS vector and lateral wall MUR.

To evaluate the determinants of left ventricular filling, left ventricular filling velocity was measured by pulsed Doppler flowmetry during catheterization of the right and left sides of the heart in 37 patients with cardiac disease before and during leg elevation. During leg elevation, despite no significant change in the time constant of isovolumic relaxation (T), the peak rapid filling velocity (PVRF) increased in association with an increase in pulmonary wedge pressure (PWP), but the peak atrial filling velocity was unchanged. The PVRF correlated with the pulmonary wedge V wave — left ventricular minimum pressure difference ( r = 0.68) and in multivariate regression with both T and mean PWP (R = 0.73). These results indicate that left ventricular filling is determined by both left ventricular relaxation and left atrial pressure and that an increase in left atrial pressure changes the left ventricular filling velocity profile in a manner that mimics the pattern with normal diastolic function.

Myocardial involvement in progressive muscular dystrophy of the Duchenne type was evaluated in 19 patients using thallium-201 myocardial perfusion imaging. A qualitative analysis was performed from five projection images by three experienced physicians. Distinct perfusion defects were shown in 13 patients, especially in the LV posterolateral or posterior wall (11 patients). There was no significant relationship between the presence of perfusion defects and the skeletal muscle involvements or thoracic deformities assessed by transmission computed tomography. Extensive perfusion defects were shown in 2 patients who died of congestive heart failure 1 to 2 years after the scintigraphic study. Progression of the myocardial scintigraphic abnormalities were considered to be minimal in 7 of 9 patients who underwent two serial scintigraphic studies over 2 to 3 years. It was concluded that thallium myocardial perfusion imaging is a useful clinical technique to assess myocardial involvement in Duchenne's progressive muscular dystrophy.

In order to investigate the antianginal effects of celiprolol (NBP-582), a randomized double-blind crossover study controlled with placebo was carried out in 17 patients with stable effort angina pectoris. Multistage treadmill exercise testing was performed before and at 4, 7, and 24 hr after a single oral administration of 400mg celiprolol or placebo. The exercise testing was terminated at moderate angina pain.The treadmill exercise duration showed no statistically significant time effects or order effects either before or after administration of the test drugs.Celiprolol significantly prolonged exercise duration, time to angina, and time to onset of ST-segment depression≥0.1mV at 4, 7, and 24hr after administrationin comparison with placebo. However, there was no significant difference in time to angina disappear ance at 4, 7, and 24 hr after administration between celiprolol and placebo.Celiprolol significantly reduced systolic blood pressure at rest in a standing position and peak exercise, and peak exercise at 4 and 7hr after administration respectively in comparison with placebo. At 24hr after administration, tendency of reduction of systolic blood pressure was observed at peak exercise.There was no significant difference in diastolic blood pressure at 4, 7, and 24hr after administration between celiprolol and placebo. Celiprolol significantly reduced heart rate and pressure rate product (PRP) at peak exercise at 4, 7, and 24hr after administration in comparison with placebo.No significant difference in ST deviation was observed at peak exercise at 4, 7, and 24hr after administration between celiprolol and placebo. A tendentious or significant prolongation of alleviated exercise-induced ST depression (ST SXT) was observed at 4hr or at 7and 24hr after administration.Celiprolol significantly reduced heart rate, PRP, and ST deviation during exercise over 24hr.These results indicate that celiprolol significantly increases exercise tolerance in patients with stable effort angina pectoris over 24hr after a single oral administration of 400mg. It is concluded that celiprolol is a clinically useful antianginal agent.

心室期外収縮96心拍と, 心室内変行伝導を伴う上室期外収縮29心拍のFrank法ベクトル心電図QRS環の特徴を分析し, 両者の鑑別基準の作成を試みた。心室期外収縮は心室変行伝導収縮に比してQRS時間および空間最大ベクトル到達時間の延長, 初期描記速度の低下, 正常伝導収縮との初期ベクトル空間夾角の開大という特徴を示した。心室期外収縮を心室変行伝導収縮から鑑別する基準として, (1) QRS時間≧120msec, (2) 空間最大ベクトル到達時間≧50msec, (3) 空間速度心電図初期30msec間のQRS環最大描記速度

Echocardiographic motions of right ventricular anterior wall (RVAW) were investigated in 71 patients with Wolff-Parkinson-White (WPW) syndrome. According to the criteria of Rosenbaum et al the electrocardiograms were classified as type A in 35 patients and type B in 36. Sixteen type B patients exhibited abnormal RVAW motion, which was characterized by an early onset of the posterior movement before S1 andl also by a premature peak formation before S2. A small step or hump nearly coincident with S1 was observed in 10 of these 16 patients. These findings seem to suggest that both contraction and relaxation of RVAW begin earlier than normal due to anterior right ventricular pre-excitation. RVAW motion was normal in all of type A patients. Echocardiographic investigation of RVAW motion appears to be useful in non-invasive estimation of the site of pre-excitation, especially in type B WPW patients.

左室造影(LVG)を施行した陳旧性心筋梗塞患者52名を対象として,安静時における二次元201Tl心筋像(二次元心筋像)および201Tl心筋emission computed tomography (ECT)像のcircumferential profile解析を行ない,梗塞の部位および大きさの診断におけるECT定量解析の有用性を検討した.健常者の長軸および短軸ECT像より求めた正常下限profile curveをもとに判定した梗塞領域は, LVGにおける壁運動異常領域とよく一致し,二次元心筋像の定量解析よりも有意に診断感度および精度が向上した.短軸ECT像から求めた全左室心筋容積に対する梗塞領域容積の百分率(%infarct size)は, %ACS (percent abnormally contracting segment: LVGの拡張期左室全周長に対する無または奇異性収縮領域周囲長の比)との間に, r=0.74(p

健常成人 (NL) 20名および冠動脈疾患 (CAD) 患者52名を対象とした。多段階臥位自転車ergometer運動 (MBEX) に対するR波高変化を解析し, CADの診断あるいは重症度判定におけるその有用性について検討した。NL群とCAD群においてR波高は運動につれて減少し, 最大運動時に最も小さくなった。R波増高または不変を陽性とするBonorisらのR波高診断基準を用いたCAD診断の感度は21%であるが, ST基準による感度は65%であり, R波高基準はST基準に比し有意に低感度であった (p

For elucidation of the type of population distribution of Frank-vectorcardiographic items of normal Japanese population, forty-eight measurements were obtained from 364 healthy Japanese men in the fourth decade. These measurements were studied with Fisher's g test of normality of population distribution, which showed that normal population distribution could be assumed in only six items (12.5%)-the maximal QRS vector angle and the directional QRS-T angle in the frontal plane, RX and TZ height, OZ duration, and anteorior accession time. The frontal maximal T vector angle was regarded to have an approximately normal population distribution. In the remaining forty-one items logarithmic normalization of distribution was attempted with a transformation formula, Y=Log10 (kX+c). Being applied to Y's, the variate logarithm-transformed with an appropriate value of c, Fisher's g test accepted the null hypothesis of normality of population distribution in 27 items (56.3%); in other words, the population distribution of 27 items was lognormal. These included the magnitudes of maximal QRS and T vectors and T/QRS ratios in the three projection planes, and some of vector angles. The population distribution was usually lognormal in scalar amplitudes and ratios except for items related to Q and S waves in leads X and Y. Bimodality of distribution was seen in six items (12.5%), which consisted of the maximal QRS vector angle and the QRS-T angles in the horizontal and left sagittal planes. In these planes the maximal QRS vector and the directional QRS-T angles showed biomodality attributed to combination of two normal distributions. Three of the four QRS-T angles in these planes and also the horizontal maximal QRS vector angle were lognormalized, although a lesser degree of bimodality still remained after seemingly successful logarithmic transformation in respect to the tg statistics. Chi-square test accepted the null hypothesis of exponential population distribution in four items (8.4%), which included the depth of QX, SX, and SY, and S/(S+R) ratio in lead Y. Exponential approximation appeared much better than normal one in the rest of measurements related to Q and S waves in leads X and Y. The following conclusions were drawn from the present study: i) statistical tests based on normal population distribution should be carefully applied to Frank-vectorcardiographic measurements of healthy Japanese men in the fourth decade and, presumably, of healthy Japanese adults regardless of age and sex; and ii) logarithmic transformation is an efficient means to normalize a skewed distribution in the majority of measurements.

健常成人の体表面電位図のKarhunel Loeve展開による基底ベクトルを用い,心肥大を持つ患者の電位図における展開係数を求め各基底ベクトルと局所心筋の興奮との対応を検討した.第一基底ベクトルは後から前へ向い,中隔肥大のQRS初期で展開係数が増大,第二基底ベクトルは右上から左下へ向い左室肥大のQRS中期で展開係数が増大,第三基底ベクトルは左上から右下へ向かい右室肥大のQRS中期で展開係数が増大した.このことから第一基底ベクトルは心室中隔,第二基底ベクトルは左室前側壁,第三基底ベクトルは右室の興奮とよく対応することが示唆された.これらを利用して心筋局所の電気現象の変化を捉えやすくすることが期待できると考えられた.

The efficacy and overall safety of levocarnitine chloride (LC-80) in treatment of patientswith ischemic heart disease (effort angina, effort and rest angina, and silent myocardialischemia), were investigated, using serial multistage treadmill exercise test, and were comparedwith that of dilazep hydrochloride used as the control treatment, by the method ofmulticenter double-blind, group comparison study. The results obtained were as follows.1. The study comprised 166 patients, with 134 of them compared for efficacy, 166 for safety, and 112 for overall usefulness.2. Global improvement: “better than ‘moderately improved’ ” was the finding in 45.6%of the levocarnitine chloride-treated group (LC group) and in 33.3% of the dilazephydrochloride-treated group (D group). There was no significant difference in globalimprovement between these two groups.3. Overall safety: no problem was observed in 95.0% of the LC group, and 95.3% of the D group.No patient in the LC group had to discontinue the test, but two patients inthe D group did so.4. Overall usefulness: “better than ‘useful’ ” was the finding in 43.7% of the LC group andin 31.0% of the D group.In the X2 test, no significant difference in overall usefulnessbetween these two groups was observed, but in the U test, significant difference wasnoted.5. Overall evaluation of the findings of exercise electrocardiogram: “better than ‘moderatelyimproved’” was the finding in 46.3% of the LC group, and in 30. 3% of the Dgroup.There was no significant difference in overall evaluation of the findings ofexercise electrocardiogram between these two groups.6. The maximal exercise duration was prolonged in the LC group compared to pre-treatmentlevels, but in the D group such prolongation was not observed. However, therewas no significant difference in the maximal exercise duration between these two groups.7. The time to onset of the 1mm ST segment depression was significantly prolonged inthe LC group after the treatment. This prolongation was not observed in the D group.However, there was no significant difference in the time to onset of the 1mm ST segmentdepression between these two groups.8. The extent of ST depression after the treatment was significantly improved in the LCgroup, when compared at the same period of exercise, but there was no significantimprovement in the D group.There was no significant difference in the extent of STdepression after the treatment between these two groups.9. Side effects: four patients (5.0%) complained of side effects in the LC group, and fivepatients (5.8%) complained in the D group.But no severe case was reported.10. Abnormal laboratory findings: GOT and LDH levels increased in one case in the LCgroup ; on the other hand, CPK level increased in one case in the D group.Neitherwas clinically significant.The results suggested that the treatment with levocarnitine chloride (LC-80), administeredat a level of 1, 800 mg/day (in 3 doses), improved significantly the exercise tolerancecapability in patients with ischemic heart disease (effort angina, effort and rest angina, andsilent myocardial ischemia), and is as useful as, or more useful than dilazep hydrochloride.We concluded that levocarnitine chloride is a clinically useful drug for the treatment ofischemic heart disease.

Aprindine hydrochloride was administered orally to 10 patients with ventricular premature contractions in dosages of 10mg and/or 20mg at intervals of 8 hours. Plasma concentration was analyzed to clarify the process of reaching the steady state and the subsequent elimination state. The plasma concentration reached steady statewithin one to two weeks. There were very little diurnal and day-to-day variations in the plasma concentration, so a stable therapeutic level was maintained. Increased dosages from 30 to 60 mg per day resulted in threefold plasma concentration increase from 0.28 to 0.89μg/ml in steady state. The decline of aprindine hydrochloride after the last dose deviated from first-order kinetics, showing a convex decreasing curve on semilogarithmic graph paper.These results demonstrate nonlinear pharmacokinetics for aprindine hydroch loride.

NT-1 is a transdermal tape containing 5 mg nitroglycerin and is expected to havesustained efficacy of nitroglycerin.In order to compare the antianginal effects of 5mg NT-1 and 10 mg NT-1 on exercisetolerance, a ramdomised double-blind cross-over study was carried out in 19 patientswith stable effort angina pectoris. Multistage treadmill exercise testing was performedin all patients before and at 2 hours after a single topical application of 5 mg NT-1 or 10mg NT-1. It was also performed in 12 out of the 19 patients, as a open study, before andat 2 hours after a single topical application of a placebo tape. The exercise testing wasterminated at moderate anginal pain.Before topical application, there were no significant differences in treadmill exerciseduration, heart rate, systolic blood pressure, or ST deviation between 5 mg NT-1 or 10mg NT-1. At 2 hours after the application, systolic blood pressure at rest was morereduced with 10 mg NT-1 than with 5 mg NT-1. However, there were no significantdifferences in treadmill exercise duration, heart rate, systolic blood pressure at peakexercise, or ST deviation between 5 mg NT-1 and 10 mg NT-1. At 2 hours after a singletopical application of NT-1, the mean plasma level of nitroglycerin was twice as highwith 10 mg NT-1 as with 5 mg NT-1.In all 12 patients who were subjected to the placebo open study, treadmill exerciseduration was significantly longer with NT-1 than with placebo, irrespective of dosagestudied. However, there were no significant differences in systolic blood pressure, pressure-rate product, or ST deviation at peak exercise between NT-1 and placebo.These results indicate that the topical application of NT-1 significantly increasesexercise tolerance in patients with stable effort angina pectoris, and that the antianginaleffects of 5 mg NT-1 are approximately equal to those of 10 mg NT-1.

心筋梗塞発生の risk factor として従来から高血圧症, 高脂血症, 糖尿病, 肥満, 喫煙などが報告されている. 本論文では急性心筋梗塞660例と対照群18,117例の臨床データを retrospective に比較することにより, これら risk factor の意義およびその性差, 年齢差について検討を行った. 喫煙者, 高血圧, 高 cholesterol 血症は対照群に比べて梗塞群で有意に多くみられたことから, これらの risk factor は従来の報告どおり心筋梗塞発症の重要な risk factor であると考られた. ついで糖尿病も risk factor の一つと考えられた. 一方肥満の程度は梗塞群と対照群の間に有意差をみとめず, 肥満のみでは risk factor となりえないという結果をえた. 高 triglyceride 血症も独立した risk factor としての意義はうすく, 肥満とともに間接的な risk factorであると考えられた. Risk factor の性差に関して, 糖尿病や高 cholesterol 血症では梗塞群と対照群間の有意差の程度が女性よりも男性で大であった. このことは女性における閉経と関係があると考えられる. 女性における estrogen などの内分泌因子が本来の risk factor のもつ危険性を低下させることにより, 血管のアテローム硬化を抑制し, ひいては梗塞発症の risk を低下させるものと考えられる. 以上から糖尿病や高 cholesterol 血症などの risk factor の重要性は女性よりも男性で大きいと考えられた. Risk factor の年齢差に関して, 多くの risk factor は老年者よりも若年者の梗塞群で有意に高率にみられた. このことは多くの risk factor を持つ若年者では血管のアテローム硬化が早期に進展し, 梗塞発症に至るばかりでなく, 他の疾患 (脳血管障害, 心不全, 腎不全など) にも罹患しやすく比較的若年で淘汰されるものと考えられる. 一方 risk factor を有しない者は老年まで生きのびるが, やがては冠動脈硬化をきたし, 梗塞発症に至るためと考えられる.以上から risk factoor の重要性は老年者よりも若年者で大きいと考えられた.

In order to investigate the effect of isosorbide 5mononitrate (5-ISMN) on exercise tolerance, a controlled study was carried out in 11 patients with effort angina pectoris. Multistage treadmill exercise testing was performed before, and 2, 4, and 7 hours after a single oral dose of placebo at 9: 30 to 10 o'clock in the morning. Two to seven days later, the test was again performed with the test drug (TY-10368) containing 20 mg of 5-ISMN according to the identical test protocol. It was terminated at moderate anginal pain.Before administration, there were no significant differences in treadmill exercise duration, pressure-rate product (PRP), and ST deviation between TY-10368 and placebo.At 2, 4, and 7 hours after the administration, the exercise duration was significantly longer after TY-10368 than after placebo (P

Mexiletine is a new antiarrhythmic agent which resembles to lidocaine electrophysiologically and is available for oral use. We investigated pharmacokinetic parameters and clinical effects on ventricular premature contractions (VPCs) of a single dose of mexiletine in 27 patients with frequent VPCs. The maximum concentration (Cmax) and the area under the time-concentration curve (AUC) increased dose-dependently, and the time to the maximum concentration after oral administration was 3.0 hours. There were significant correlations between dosage (mg/kg) and Cmax (r=0.87, p

A correlative study was performed on 70 patients with old anterior myocardial infarction between each of the orthogonal components of instantaneous QRS vectors and the anterior-wall, lateral-wall and septal myocardial uptake ratios (A-MUR, L-MUR, and S-MUR, respectively). These MURs were calculated from the thallium-201 myocardial perfusion images at 5 projections and used as the index of the infarct size of the respective LV wall. The Z components of the 14-msec and 24-msec instantaneous QRS vectors significantly correlated with the S-MUR (r = -0.51) and the A-MUR (r = -0.66) respectively. The X component of the 32-msec instantaneous QRS vector also showed a significant correlation with the L-MUR (r = 0.59). The regression equations obtained in the present study seemed also applicable to patients with complete right bundle branch block. It is concluded that the quantitative analysis of the Frank vectorcardiograms could afford valuable information as to the size as well as the site of myocardial infarctions.

To define the clinical significance of T wave map changes in patients with angina at rest, body surface isopotential T distributions were obtained in 48 patients with single-vessel disease (left anterior descending artery, 34; right coronary artery, eight; left circumflex artery, six) documented angiographically and were compared with those in 120 healthy subjects and those in 19 patients with left ventricular overload whose electrocardiograms showed negative T waves accompanied by an increase in R wave amplitude in left precordial leads. The T wave map abnormalities were observed in 24 of 48 patients (50%) with angina and were classified into three types: (1) type I (18 patients, 37.5%) was characterized by a segmental negative potential in the positive area located at the left thorax and the minimum at the peak of T wave positioned in the upper portion of the left anterior chest, (2) type II (three patients, 6.3%) was characterized by a negative potential with a minimum in the inferior thorax and an indentation of negative potential at the lower margin of the positive potential located over the upper thorax, and (3) type III (three patients, 6.3%) was characterized by a negative potential with a minimum at the back throughout the period of T wave. All patients showing T wave map abnormalities of type I had a significant stenosis of the left anterior descending artery. Likewise, all patients with type II or III had single-vessel disease of the right coronary or left circumflex artery, respectively. All types of T wave map changes observed in patients with angina were different from those in patients with left ventricular overload, whose maps showed the generalized negative potential at the inferior thorax and the left back and the minima clustered at the precordium. In seven patients with lesions of the left anterior descending artery, T wave map abnormalities of type I recovered to normal after successful percutaneous transluminal coronary angioplasty. The behavior of the negative potential and its extrema on the T wave map, which was not available from routine electrocardiography, was indicative of the involved coronary artery and probably of its associated ischemic area in one-half of our patients with angina pectoris.

Body surface potential maps were recorded for 52 patients with solitary anterior myocardial infarction and 57 normal subjects. All patients had pure anterior wall asynergy on a left ventriculogram but no diagnostic Q wave on the standard 12-lead electrocardiogram. Q wave (greater than 30 msec) distributions on the body surface of the patients and normals were compared. The frequency of Q waves in the area above V1-V2 and in the right middle chest was significantly higher in patients than in normals. The sensitivity of Q waves for asynergy in leads from both these areas was 19-60%. The positive predictive value was 67-94%. The frequency of Q waves was significantly higher in severe asynergy than in mild asynergy. A combination of two selected unipolar leads from these areas yielded a sensitivity and specificity of 33% and 95%, respectively. With a combination of three leads, these values were 42% and 93% and with four leads 48% and 88%, respectively. The results indicate that several unipolar leads from the area above V1-V2 and from the right middle chest in addition to the standard 12-lead electrocardiogram may improve the electrocardiographic diagnostic accuracy of myocardial infarction.

The effects of elastase on lipid metabolism, platelet function, and blood coagulability were evaluated in 18 patients with diabetes mellitus. Blood sampling was made before medication, and after oral administration of 10800 units of elastase per day 8 and 16 weeks. Measurements were made for platelet counts, platelet sensitivity to ADP-aggregation, serum concentrations of total cholesterol·HDL-cholesterol·triglyceride and plasma concentrations of, β-thromboglobulin (β-TG)·fibrinogen (Fbg)·antithrombin III (AT III).After the administration of elastase, HDL-cholesterol increased (0W: 45.6±10.3mg/dl; 8W: 49.2±10.1mg/dl, p

To investigate hemodynamic effects of a new coronary vasodilator, 2-nicotinami doethyl nitrate (nicorandil), 12 patients with prior myocardial infarction were stu died. Patients with angina pectoris were excluded.Hemodynamic measurements were made during supine bicycle ergometer exercise testings before and 60 min after single oral administration of 15 mg of nicorandil. Symptom-limited exercise testing was performed before nicorandil, and after nicoran dil the same workload was assigned to each patient. At peak exercise, there was a significant increase in cardiac index, while stroke volume index remained unchanged after nicorandil. Both at rest and at peak exercise, there was a significant decrease in systolic and diastolic blood pressure, systemic vascular resistance, and pulmonary capillary wedge pressure after nicorandil. Coronary sinus blood flow was significant ly increased and coronary vascular resistance was significantly decreased after nicor andil both at rest and peak exercise. The average value for plasma nicorandil concen tration was 215ng/ml 60min after dosing.These data would indicate that nicorandil exhibits a beneficial effect on hemodyna mic responses to exercise in patients with prior mycoardial infarction by reduction of left ventricular preload and afterload and by increment in coronary blood flow.

The present status of exercise testing in coronary artery disease (CAD) was discussed in respect to test protocols, ECG criteria and lead systems, and hemodynamic responses. Advantages of modern multistage protocols over single-stage ones such as Master two-step tests are obvious in diagnostic accuracy and patient's safety. Clinical significance of horizontal and downsloping ST depression has already been established. Diagnostic significance of other exercise-induced ECG alterations such as slow upsloping ST depression, ST elevation, U-wave inversion, and R-wave amplitude changes was discussed. The latter parameter is still controversial as to its clinical significance. Use of an inadequate ECG lead system is one of major causes of false negative tests. Necessity of multiple lead systems was emphasized for higher diagnostic accuracy. From the view point of cost-efficacy relation, we will recommend simultaneous recording of CC5 or CM5, V3 and CL or III in routine exercise testing for screening of CAD. Test results such as exercise time, and heart rate and systolic blood pressure responses are also useful parameters for the evaluation of the severity and prognosis of CAD. It was emphasized that in exercise monitoring of ECG and blood pressure is indispensible in multistage exercise testing for improvement of diagnostic accuracy as well as patient's safety.

In order to investigate the antianginal effects of a new calcium antagonist, nilvadipine, a randomized double-blind cross-over study controlled with placebo wascarried out in 15 patients with stable effort angina pectoris. Multistage treadmillexercise testing was performed before, and at 2, 4, and 7 hours after a single oraladministration of 6 mg nilvadipine or placebo. The exercise testing was terminated atmoderate anginal pain.The treadmill exercise duration showed no statistically significant time effects ororder effects either before or after administration of the test drugs. Before administration, there were no significant differences in exercise duration, time to onset of STsegment depression≥0.1 mV, pressure-rate products, or ST deviation between nilvadipine and placebo.Nilvadipine significantly prolonged exercise duration at 2, 4, and 7 hours after dosing, and time to onset of ST-segment depression≥0.1 mV at 2 and 4 hours after dosing.However, there were no significant differences in ST deviation at peak exercise betweennilvadipine and placebo.Nilvadipine significantly reduced resting systolic blood pressure at 2 and 4 hoursafter dosing. At peak exercise, nilvadipine significantly increased heart rate at 2 and 7hours, and pressure-rate product at 2 hours after dosing, respectively.These results indicate that nilvadipine significantly increases exercise tolerance inpatients with stable effort angina pectoris up to 7 hours after a single oral administrationof 6 mg. It is concluded that nilvadipine is a clinically useful antianginal agent.