Tatsuyuki Matsunami

Mechanism of abnormal postexercise systolic blood pressure response and its diagnostic value in patients with coronary artery disease

To define the factors that affect an abnormal postexercise systolic blood pressure (SBP) response and to verify the diagnostic value of that response in patients with coronary artery disease (CAD), we studied 33 normal subjects, eight patients with hypertension who had no CAD, and 42 patients with documented CAD who underwent supine leg exercise testing. SBP recovery ratios were derived by dividing the values obtained 1 and 3 minutes after exercise by the peak value. The upper normal limit of the SBP ratio was defined by two standard deviations from the mean for 33 normal subjects. The specificity of this criterion for identifying patients with CAD was 97% and the sensitivity was 60%. None of the eight patients with hypertension showed an abnormal postexercise SBP response. At peak exercise the pulmonary artery wedge pressure was significantly greater in the patients with CAD having an abnormal response. In multiple regression analysis the exercise pulmonary artery wedge pressure, the exercise SBP, and the systemic vascular resistance after exercise were determining factors for an abnormal SBP response. Three-vessel disease was more common in patients with an abnormal response. Results of this study indicate that an abnormal postexercise SBP response appears to be determined by (1) the extent of exercise-induced impairment of left ventricular function and (2) peripheral vascular tone during recovery. This study also suggests that this criterion can increase the specificity of supine exercise testing in patients with CAD including those with hypertension and might provide a marker for the severity of impaired left ventricular function by exercise in CAD.

Hemodynamic mechanisms of antianginal action of calcium channel blocker nisoldipine in dynamic exercise-induced angina.

To investigate the mechanism of antianginal action of the calcium channel blocker nisoldipine and to determine the reproducibility of the clinical and hemodynamic events induced by supine leg exercise, 30 patients with stable effort angina pectoris were studied. They were divided into two groups; one group of 19 patients received a single 10-mg dose of nisoldipine orally, and the other group of 11 patients received a single dose of placebo orally. Chest pain was induced in all of 30 patients during the control exercise test. After nisoldipine administration, chest pain was not induced in 13 of 19 patients and was of lessened severity in five patients with the same work load as those performing control exercise. ST segment at peak exercise showed less severe depression after nisoldipine. Systemic vascular resistance was reduced by 38% (p less than 0.001) at rest and 22% (p less than 0.001) at peak exercise, and coronary vascular resistance was reduced by 31% (p less than 0.01) at rest and 18% (p less than 0.01) at peak exercise. Pulmonary artery wedge pressure fell from 6 +/- 1 to 3 +/- 1 mm Hg (p less than 0.001) at rest and from 28 +/- 3 to 11 +/- 2 mm Hg (p less than 0.001) at peak exercise. Coronary sinus flow at rest and myocardial oxygen uptake both at rest and during exercise was not modified by nisoldipine. However, coronary sinus flow at peak exercise increased significantly from 219 +/- 24 to 249 +/- 31 ml/min (p less than 0.01) after nisoldipine, and myocardial oxygen uptake was not significantly changed despite decreased coronary vascular resistance. The clinical and hemodynamic events induced by the exercise during invasive studies (except pulmonary artery wedge pressure at rest) were reproducible after placebo administration. Our data demonstrate that increased coronary blood flow could be the major mechanism of the antianginal action of nisoldipine in supine leg exercise-induced angina.

Clinical significance of simple heart rate-adjusted ST segment depression in supine leg exercise in the diagnosis of coronary artery disease

To evaluate the clinical significance of simple heart rate-adjusted ST segment depression (delta ST/delta HR) in the diagnosis of coronary artery disease, 42 patients with stable exertional angina underwent supine leg exercise testing and cardiac catheterization. During exercise, heart rate, a multilead electrocardiogram, and pulmonary artery wedge pressure were recorded. The sensitivity and accuracy of the delta ST/delta HR criteria (greater than or equal to 3.0 microV/beat/min) were significantly greater than the conventional analysis of ST segment depression criteria (greater than or equal to 0.2 mV) for detecting three-vessel coronary artery disease at a matched specificity of 72% (100% versus 46%, 81% versus 64%, p less than 0.01). A significant linear correlation was found between maximum pulmonary artery wedge pressure increments during exercise (delta PAWP) or Gensini score and the delta ST/delta HR (delta PAWP: r = 0.51, p less than 0.001; Gensini score: r = 0.47, p less than 0.001). There were no statistically significant differences in the delta PAWP or Gensini score between patients with three-vessel disease who had delta ST/delta HR greater than or equal to 3.0 microV/beat/min and those with one- or two-vessel disease who had delta ST/delta HR greater than or equal to 3.0 microV/beat/min (delta PAWP: 18.1 +/- 2.0 versus 21.9 +/- 3.3, p = NS; Gensini score: 68.5 +/- 6.6 versus 66.3 +/- 11.3, p = NS). These findings demonstrate that delta ST/delta HR is more useful than a conventional analysis of ST segment depression for identifying not only anatomically severe coronary artery disease but also functionally severe coronary artery disease.

Effect of antianginal agents on the relationship between rate-pressure product and myocardial oxygen uptake

To evaluate the effects of antianginal agents on the correlation between rate-pressure product and myocardial oxygen uptake, multistage supine leg exercise tests were performed by 21 patients with stable effort-induced angina pectoris before and after administration of antianginal drugs (a calcium channel blocker of the dihydropyridine class [10 mg of nisoldipine orally] in 11 patients and a beta-blocker [0.2 mg/kg of propranolol intravenously] in 10 patients). The rate-pressure product was closely correlated with myocardial oxygen uptake before and after administration of each drug. However, the slope of the regression line of rate-pressure product (X) and myocardial oxygen uptake (Y) became significantly steeper after the calcium channel blocker administration, and the Y-intercept was significantly increased by administration of the beta-blocker. Myocardial oxygen uptake was increased after administration of the calcium channel blocker and the beta-blocker compared with control values at corresponding rate-pressure product. These observations should be considered when the rate-pressure product is used to predict myocardial oxygen uptake in patients with angina pectoris who are receiving antianginal drugs.

Dynamic exercise-induced elevation in plasma levels of atrial natriuretic peptide in patients with effort angina pectoris

We investigated the relationship between plasma atrial natriuretic polypeptide (ANP) levels and hemodynamic indices during dynamic exercise testing in 15 patients with effort angina pectoris. Patients exercised on an angina-limited, supine, multistage bicycle ergometer, and plasma ANP levels and hemodynamic indices were measured at rest, at peak exercise, and 6 minutes after exercise. Plasma ANP levels increased significantly at peak exercise. Pulmonary artery wedge pressure (PAWP) and coronary sinus blood flow (CSBF) were significantly correlated with plasma ANP levels before and at peak exercise (PAWP: r = 0.69, p less than 0.001; CSBF; r = 0.45, p less than 0.05). In six of eight patients whose PAWP exceeded 20 mm Hg at peak exercise, plasma ANP levels were increased at 6 minutes after exercise, whereas PAWP had decreased relative to the values obtained at peak exercise. Plasma ANP concentrations at 6 minutes after exercise were not correlated with PAWP at the same time. However, PAWP at peak exercise was correlated with the plasma ANP levels at 6 minutes after exercise (r = 0.80, p less than 0.001). These results suggest that in patients with effort angina pectoris left ventricular dysfunction resulting from exercise-induced myocardial ischemia may increase preload excessively and may contribute to the excess secretion of ANP after dynamic exercise.

Hemodynamic mechanisms of the antianginal action of a novel vasodilator FK409 in dynamic exercise-induced angina.

FK409 is a novel vasodilator with a unique chemical structure. We wished to elucidate the mechanisms of antianginal action of FK409 in dynamic exercise-induced angina. Twelve patients with stable effort angina pectoris were studied before and after a single 40-mg oral dose of FK409. Chest pain was induced in all of 12 patients during the control multistage bicycle ergometer exercise. After FK409 administration, the same workload did not induce chest pain in 6 patients. The ST segment at peak exercise showed less severe depression from 0.15 ± 0.02 to 0.05 ± 0.01 mV (p < 0.001). Left ventricular (LV) filling estimated by the Doppler method was reduced, and pulmonary artery wedge pressure decreased significantly (p < 0.001) throughout exercise testing after FK409. Myocardial oxygen uptake and coronary sinus flow throughout exercise testing decreased significantly (p < 0.05) after FK409 administration. The results of the present study demonstrate that decrease in myocardial oxygen demand may be caused by pre- and afterload reduction and that it could be a major mechanism of the antianginal action of FK409. However, other mechanisms such as redistribution of coronary blood flow to the subendocardium, direct dilatation of the stenotic parts of the epicardial arteries, and an increase in collateral blood flow should be considered additional possible mechanisms of the antianginal action of FK409.