Haruki Itoh

Detecting abnormalities in left ventricular function during exercise by respiratory measurement.

The degree of exercise-induced cardiac dysfunction and its relation to the anaerobic threshold were evaluated in 23 patients with chronic heart disease. A symptom-limited exercise test was performed with a cycle ergometer with work rate increased by 1 W every 6 seconds. Left ventricular function, as reflected by ejection fraction, was continuously monitored with a computerized cadmium telluride detector after the intravenous injection of technetium-labeled red blood cells. The anaerobic threshold (mean, 727 +/- 166 ml/min) was determined by the noninvasive measurement of respiratory gas exchange. As work rate rose, the left ventricular ejection fraction increased but reached a peak value at the anaerobic threshold and then fell below resting levels. Ejection fraction at rest, anaerobic threshold, and peak exercise were 41.4 +/- 11.3%, 46.5 +/- 12.0%, and 37.2 +/- 11.0%, respectively. Stroke volume also increased from rest (54.6 +/- 17.0 ml/beat) to the point of the anaerobic threshold (65.0 +/- 21.2 ml/beat) and then decreased at peak exercise (52.4 +/- 18.7 ml/beat). The slope of the plot of cardiac output versus work rate decreased above the anaerobic threshold. The anaerobic threshold occurred at the work rate above which left ventricular function decreased during exercise. Accurate determination of the anaerobic threshold provides an objective, noninvasive measure of the oxygen uptake above which exercise-induced deterioration in left ventricular function occurs in patients with chronic heart disease.

Beat-to-beat evaluation of cardiac function during recovery from upright bicycle exercise in patients with coronary artery disease

The purpose of this study was to evaluate the time course of cardiac function during recovery from upright bicycle exercise in patients with coronary artery disease. Twelve patients with coronary artery disease performed a symptom-limited exercise test on a cycle ergometer. Left ventricular function was continuously monitored during exercise and recovery with a computerized cadmium telluride detector following the intravenous injection of technetium-labeled red blood cells. Although the end-diastolic volume (153.4 +/- 76.1 ml) and end-systolic volume (100.5 +/- 67.3 ml) at the end of exercise were significantly higher than the respective resting values, stroke volume (52.8 +/- 16.1 ml) and ejection fraction (38.0 +/- 12.2%) were not different from the respective resting values. The recovery of cardiac output was relatively slow compared with that of heart rate, because stroke volume rose sharply early in recovery. The rise in stroke volume was chiefly a result of a significant decrease in end-systolic volume between 1 and 4 minutes of recovery. These changes may result from an immediate afterload reduction coupled with a relatively slow decrease in sympathetic stimulation. The time course of cardiac function during recovery from exercise in cardiac patients is substantially different from that of normal subjects and may be a sensitive way to evaluate the peripheral vascular function and deteriorated cardiac function in cardiac patients.

Cardiac output-O2 uptake relation during incremental exercise in patients with previous myocardial infarction.

BACKGROUND The cardiac output-O2 uptake (VO2) relation, which is thought to be linear and predictable in normal humans, has not been clarified in cardiac patients. We evaluated the relation between cardiac output and VO2 during the incremental exercise test in patients with previous myocardial infarction. METHODS AND RESULTS Twenty-two patients (age, 58.1 +/- 8.0 years) with previous myocardial infarction performed a symptom-limited exercise test on a cycle ergometer. VO2 was calculated from the expired gas analysis, and cardiac output was measured by a computerized cadmium telluride detector every 10 seconds during exercise. The ratio of increase in VO2 to the increase in work rate (delta VO2/delta WR) below and above the anaerobic threshold (AT) was 11.1 +/- 3.6 and 11.1 +/- 2.9 ml/min/W, respectively, showing no significant difference. However, the ratio of increase in cardiac output to increase in work rate (delta CO/delta WR) below the AT was 50.1 +/- 26.6 ml/min/W and was significantly decreased to 11.8 +/- 25.3 ml/min/W above the AT (p = 0.0002). The decreased delta CO/delta WR above the AT primarily would be due to silent myocardial ischemia produced by exercise, as there was the presence of 201Tl redistribution in 15 of 16 patients in whom myocardial 201Tl scintigraphy with dipyridamole or exercise stress testing was evaluated. delta CO/delta VO2, which has been reported to be approximately 5.5 in normal subjects, was only 4.4 +/- 2.6 at work rates below the AT and was decreased to 1.1 +/- 2.3 at work rates above the AT. CONCLUSIONS The relation between cardiac output and VO2 during exercise in patients with previous myocardial infarction differs profoundly from that reported in normal subjects. These findings must be considered when we noninvasively estimate the change in cardiac output during exercise by obtaining VO2 in patients with coronary artery disease.

Hemodynamic Effects and Pharmacokinetics of Long-Term Therapy with Ibopamine in Patients with Chronic Heart Failure

To evaluate the attenuation of the effectiveness of long-term ibopamine therapy, ibopamine was administered in single doses of 100 and 200 mg to 10 patients with chronic heart disease. The hemodynamic studies using Swan-Ganz catheter and pharmacokinetic studies were carried out. Ibopamine was found to increase cardiac output and stroke index and to decrease systemic vascular resistance in this acute study. Six patients underwent long-term therapy with the drug and were evaluated for the development of tolerance. Three out of 5 patients experienced an improvement in NYHA functional class after 12-23 weeks of treatment. There was no attenuation in the effects of ibopamine on hemodynamics, pharmacokinetic parameters remained almost unchanged, and tolerance was not observed. These results suggest that ibopamine is useful as an orally administered anti-heart failure drug.

Effects of enoximone on exercise tolerance in patients with mild to moderate heart failure

To evaluate the efficacy of enoximone on exercise tolerance in patients with mild to moderate heart failure, 33 patients underwent cardiopulmonary exercise tests before and 3 hours after placebo or after receiving 25 or 100 mg of enoximone administered randomly in a double-blind manner. The electrocardiogram was monitored and blood pressure measured every minute throughout cycle ergometer exercise testing with a ramp protocol in which the work rate increased 1 W every 6 seconds after a 4-minute 20-W warm-up. Minute ventilation, oxygen uptake (VO2), and carbon dioxide output were measured every 10 seconds in order to determine anaerobic threshold (AT) and peak VO2. Five patients were excluded from evaluation before breaking the double-blind key because of insufficient data. Heart rate increased and systolic blood pressure decreased throughout the testing only in the group taking 100 mg (n = 10). Significant increases in AT (14.4 to 16.2 ml/min/kg) and peak VO2 (20.8 to 22.9 ml/min/kg) were observed in the group taking 100 mg. The increases in AT showed a dose response, namely +0.7% in the placebo (n = 9), +6.9% in the 25-mg (n = 9) and 12.5% in the 100-mg group. The work rates at the AT point increased in the 25- and 100-mg groups. These results indicate that a single oral administration of enoximone improves exercise tolerance in patients with mild to moderate heart failure.

Differences between vasorelaxant responses of the canine and human mesenteric arteries and veins to amrinone

Amrinone induced similar degrees of relaxation in human mesenteric arteries and veins contracted with KCl, but exerted a more potent vasodilator effect in canine mesenteric veins than in arteries. Dibutyryl cAMP had a stronger effect on KCl-induced contraction in canine mesenteric veins than in arteries. These results suggest that amrinone promotes a different vasodilating action in human and canine mesenteric vessels, possibly via different sensitivity to cAMP in each vascular smooth muscle.

Hemodynamic Comparison of Combined Therapy by Nitroglycerin Tape and Ibopamine with Combination of Nitroglycerin Tape and Nifedipine

Fifteen congestive heart failure patients (NYHA: class III or IV) were enrolled in the study and were classified into two groups. Six patients (group I) received combined therapy by nitroglycerin tape (5 mg) and ibopamine (100 mg), while the remaining 9 patients (group II) were given nitroglycerin tape (5 mg) and nifedipine (10 mg). The effects of the combined treatments on hemodynamics were compared between the two groups using Swan-Ganz catheter method. No significant differences were noted in the hemodynamic baseline values of the two groups before treatment. In group I mean pulmonary arterial pressure (mPA) and systemic vascular resistance (SVR) decreased and the cardiac index (CI) increased, while the heart rate (HR) and mean blood pressure (mBP) remained unchanged. In group II mBP, mPA and SVR were lowered, whereas CI and HR were augmented. There were no significant differences between the two groups with respect to mPA and CI. However, mBP decreased in group II, while it remained unchanged in group I, with significant difference between the two groups (p less than 0.01). Preload and afterload, on the base of mPA and SVR, respectively, decreased in both groups, while cardiac output increased, suggesting that both treatments were useful for the improvement of cardiac output. Mean BP decreased in group II, although it remained unchanged in group I. These results suggest that the combination of nitroglycerin and ibopamine may be more useful in hypotensive patients with heart failure.