Atsushi Tsunekawa

Effects of a new vasodilator, nicorandil, on exercise-induced impairment of left ventricular function in patients with old myocardial infarction.

Hemodynamic effects of nicorandil on exercise-induced impairment of left ventricular function were studied in nine patients with old myocardial infarction but without angina pectoris. Hemodynamic data were obtained by symptom-limited supine multistage bicycle ergometer exercise testing before and 1 h after single oral administration of 15 mg of nicorandil. Systolic and diastolic blood pressure at rest decreased significantly after nicorandil administration (p < 0.01). A most remarkable change in the hemodynamic response to supine dynamic exercise after nicorandil was a decrease in pulmonary artery wedge pressure (both at rest and at peak exercise, p < 0.001). An index of cardiac function, obtained from the relation between pulmonary artery wedge pressure and left ventricular stroke work index, improved significantly after nicorandil. The ratio of pressure-rate product to coronary sinus flow, which is an index of the ratio of myocardial oxygen consumption to myocardial oxygen supply, decreased significantly (p < 0.05) after nicorandil administration. Reproducibility of the testings was also studied in six patients with old myocardial infarction. Invasive hemodynamic variables between two successive symptom-limited supine leg exercise testings, except pulmonary artery wedge pressure, were reproducible in patients with old myocardial infarction but without angina pectoris. Only pulmonary artery wedge pressure at rest in the second exercise testing showed a significantly lower value (p < 0.05). It is concluded that nicorandil is a useful drug for improvement of exercise-induced impairment of left ventricular function with an increase in myocardial oxygen supply.

Lack of Association of Angiotensin Converting Enzyme Gene Polymorphism or Serum Enzyme Activity With Coronary Artery Disease in Japanese Subjects

The association of an insertion/deletion (I/D) polymorphism in the angiotensin converting enzyme (ACE) gene or the serum activity of ACE with coronary artery disease (CAD) was investigated in Japanese men and women. The ACE genotype of 947 CAD subjects who underwent coronary angiography and of 893 control subjects was determined by polymerase chain reaction analysis. No association of the DD genotype or the D allele with CAD was observed in men or women. In a low risk group (defined by a body mass index below the median value and the absence of a history of hypertension, diabetes mellitus, and hypercholesterolemia), there was also no association between the ACE gene polymorphism and CAD. No significant difference in serum ACE activity was detected between CAD subjects and controls of all genotypes or of the same genotype, whereas a significant association was apparent between serum ACE activity and ACE genotype for both CAD subjects and controls among both men and women. These results indicate that the ACE I/D polymorphism and genotype associated variation in serum ACE activity are not risk factors for CAD in Japanese men or women.

Effects of isosorbide-5-mononitrate on exercise-induced hemodynamic changes in angina pectoris

Hemodynamic effects of isosorbide-5-mononitrate (ISMN) were studied in 14 patients with effort angina pectoris. Hemodynamic and echocardiographic data were obtained by angina-limited supine multistage bicycle ergometer exercise testing before and 120 minutes after single oral administration of 20 mg of ISMN. Compared with control exercise testing, the ST segment at peak exercise showed less depression after administration of ISMN (p less than 0.001). At rest, systolic and diastolic blood pressure decreased significantly after administration of ISMN (p less than 0.001 and p less than 0.01, respectively). At rest and at peak exercise, pulmonary artery wedge pressure (both p less than 0.001), left atrial volume (both p less than 0.001) and left ventricular end-diastolic volume (both p less than 0.05) decreased, whereas cardiac index, pressure-rate product and systemic vascular resistance did not change significantly after administration of ISMN. Average time to peak plasma ISMN concentration was 90 minutes and average peak plasma concentration was 460 ng/ml with an elimination half-life of 7 hours. These data suggest that the main mechanism of the antianginal action of ISMN is a reduction in left ventricular preload followed by diminution of myocardial oxygen requirements.

Effects of a new second generation calcium channel blocker, nilvadipine (FR34235), on exercise-induced hemodynamic changes in stable angina pectoris.

The mechanism of the antianginal actions of nilvadipine was investigated in 11 patients with effort angina pectoris. Hemodynamic data were obtained by angina-limited supine multistage bicycle ergometer exercise testing before and after a single 6 mg dose of nilvadipine. Compared with chest pain during control exercise testing, pain at peak exercise disappeared or abated and the ST segment at peak exercise also showed less significant depression after administration of nilvadipine. At rest and at peak exercise, mean blood pressure, pulmonary artery wedge pressure and systemic vascular resistance decreased significantly, whereas heart rate and cardiac index increased significantly after nilvadipine. Rate-pressure product and stroke volume index did not change significantly. Coronary sinus flow at peak exercise increased significantly and total coronary vascular resistance at rest and at peak exercise decreased significantly after nilvadipine. The plasma concentrations of nilvadipine 1.5 hours after administration ranged from 1.15 to 8.23 ng/ml. These data suggest that the principal factors in the antianginal actions of nilvadipine are an increase in myocardial oxygen supply due to increased coronary blood flow and a reduction in myocardial oxygen demand mainly by a decrease in afterload and additionally by a decrease in preload.

Association of a Deletion Polymorphism of the Angiotensin-Converting Enzyme Gene with Left-Ventricular Hypertrophy in Japanese Women with Essential Hypertension; Multicenter Study of 1,919 Subjects

The relationship of an insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene to left-ventricular hypertrophy in individuals with essential hypertension (EH) was investigated in a large population of Japanese men and women. The ACE genotype of 762 subjects with EH (425 men and 337 women) and 1,157 healthy controls (604 men and 553 women) was determined by polymerase chain reaction analysis. The distribution of ACE genotypes did not differ significantly between patients with EH and control in both men and women. For women with EH, the DD genotype was positively associated with the thickness of the interventricular septum and inversely associated with the left ventricular end-diastolic dimension, both determined by echocardiography. In contrast, the DD genotype was not associated with any echocardiographic parameter in men with EH. These results indicate that the DD genotype is a risk factor for left-ventricular hypertrophy in Japanese women with EH, but not for Japanese men.

Exercise P-vector magnitude changes in angina pectoris: frank-vectorcardiographic and hemodynamic correlations

Multistage bicycle ergometer exercise testings with Frank vectorcardiogram and M-mode echocardiogram were performed on 12 patients with effort angina pectoris. The left atrial and left ventricular end-diastolic volume (LAV and LVEDV) were calculated as a cube of the left atrial and left ventricular end-diastolic dimension. The mean pulmonary artery wedge pressure (mPAWP) was measured with a Swan-Ganz catheter during the testing. At peak exercise a statistically significant increase was observed in mPAWP (p less than 0.001), LAV (p less than 0.005), the maximal horizontal P-vector magnitude (Hmax) (p less than 0.05) and the percent change in Hmax (%Hmax). %Hmax showed a significant correlation with the increment of mPAWP (delta mPAWP) (r = 0.66, p less than 0.05), the increment of LVEDV (delta LVEDV) (r = 0.83, p less than 0.01) and the increment of LAV (delta LAV) (r = 0.81, p less than 0.001). Multiple regression analysis was performed on %Hmax as a dependent variable with delta LAV, delta mPAWP, and the increment of heart rate (delta HR) as independent variables (r = 0.84, p less than 0.05), but the partial correlation coefficients of delta mPAWP and delta HR were not significant. The present study demonstrated that the increase in Hmax had a close relationship with the increase in mPAWP and LVEDV and that the preload of the left ventricle during exercise-induced anginal attack could be predicted noninvasively by %Hmax. The increase in Hmax was thought to be due to the increase in LAV during anginal attack.

Hemodynamic determinant factor of exercise tolerance in patients with prior myocardial infarction

左室駆出分画(LVEF)が50%未満に低下しているにもかかわらず良好な運動耐容能を示すとともに狭心症を認めない陳旧心筋梗塞患者(II群; 13例)における運動耐容能の規定因子を究明するために,障害群と同等の運動耐容能を有しLVEF50%以上の陳旧心筋梗塞患者(I群; 13例)を対照として仰臥位多段階自転車ergometer運動試験を施行した. peak運動時心係数は両群間に有意差を示さなかった.運動時間を従属変数とする重回帰分析にて, I群では運動時心拍数および平均肺動脈楔入圧の増加分が, II群では運動時末梢血管抵抗の減少分および心拍数の増加分が高い寄与度を示した.以上より, I群に比しII群では運動時の後負荷減少が運動耐容能の重要な規定因子であると考えられた.