Author + information
- Received April 26, 1994
- Revision received August 16, 1994
- Accepted August 25, 1994
- Published online February 1, 1995.
- Kohzo Nagata, MD,
- Mitsunori Iwase, MD, PhD,
- Toshikazu Sobue, MD and
- Mitsuhiro Yokota, MD, PhD, FACC∗
- ↵∗Address for correspondence: Dr. Mitsuhiro Yokota, Cardiovascular Section, Department of Clinical Laboratory Medicine, Nagoya University School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466, Japan.
Objectives. This study was designed to compare the influence of beta-adrenergic stimulation (dobutamine) and a selective phosphodiesterase inhibitor (MS-857) on left ventricular diastolic performance and Doppler transmitral flow velocity patterns in patients with congestive heart failure and to elucidate the mechanisms for changes in early diastolic filling induced by each agent.
Background. Both beta-adrenergic agonists and phosphodiesterase inhibitors act through the cyclic adenosine monophosphate pathway. However, it is controversial whether they have similar effects on diastolic performance. No previous studies have investigated the effects of these agents on Doppler-derived measurements of diastolic filling. We hypothesized that they would have different effects on early diastolic filling in patients with congestive heart failure.
Methods. Twenty patients with chronic congestive heart failure resulting from idiopathic dilated cardiomyopathy were randomized to receive intravenous infusion of dobutamine (5 μg/kg body weight per min, n = 10) or oral administration of MS-857 (15 mg, n = 10). Transmitral flow velocity patterns were obtained with simultaneous recordings of pressure-volume loops using a conductance catheter with a micromanometer tip before and after drug administration.
Results. Left ventricular filling pressure was reduced by both agents. Dobutamine decreased the time constant of isovolumetric relaxation and increased the difference between pulmonary artery wedge pressure at the peak of the vwave and left ventricular minimal pressure (10 ± 3 to 12 ± 4 mm Hg, p < 0.01) and peak early filling velocity (47 ± 7 to 56 ± 11 cm/s, p < 0.01). The diastolic pressure-volume relation showed a leftward shift in all patients. In contrast, MS-857 did not affect the time constant but maintained the pressure difference (9 ± 3 to 8 ± 3 mm Hg, p = NS) and peak early filling velocity (50 ± 7 to 49 ± 12 cm/s, p = NS). The diastolic pressure-volume relation after MS-857 showed a downward shift in most patients.
Conclusions. These results indicate that beta-adrenergic stimulation and phosphodiesterase inhibitors have different effects on early diastolic filling through different mechanisms in patients with congestive heart failure.
☆ This support was supported in part by research grants for cardiovascular diseases (4A-4) from the Ministry of Health and Welfare and by grants-in-aid for scientific research (06670706) from the Ministry of Education, Science, and Culture of Japan, Tokyo. It was presented in part at the 66th Scientific Sessions of the American Heart Association, Atlanta, Georgia, November 1993.
- Received April 26, 1994.
- Revision received August 16, 1994.
- Accepted August 25, 1994.