Left ventricular function after oral milrinone in patients with congestive heart failure. A hemodynamic and angiographic study
The diastolic properties of the left ventricle (LV) are important determinants of cardiac function; alteration in diastolic function accounts for many of the clinical manifestations of congestive heart failure. Changes in myocardial relaxation and filling phases, changes in coronary blood flow, diastolic tone and ventricular shape all contribute to the abnormal diastolic compliance of the failing heart. To assess the short-term effects of a single oral dose (10 mg) of milrinone (M) on diastolic function, 14 patients (pts), mean age 59 ± 6 years, with severe congestive heart failure underwent this study. After baseline hemodynamic measurements, LV angiography with simultaneous recording of LV pressure (tip-manometry) and pressure-derived parameters was performed at paced heart rate (15 beats above spontaneous heart rate). After repeat baseline measurements, M was administered followed by LV pressure measurements at 10′ intervals to 50′ together with coronary blood flow measurement. Blood samples to determine the plasma concentration of M were withdrawn at the same intervals. Blood arterial and coronary sinus samples for catecholamine levels and oxygen saturations were withdrawn before and 50′ after M. LV angiography was repeated 60′ after M at matched atrial paced rates with simultaneous pressure recordings. During the first phase of the study, peak negative dP/dt progressively and significantly increased from 827 ± 209 to 904 ± 194mm Hg/sec (p < 0.01) whereas LV systolic pressure slightly decreased. The time constant of early relaxation, Tau1,(fit for the first 40 msec. after the occurrence of peak negative dP/dt), decreased progressively and significantly from 71 ± 17 to 58 ± 14 msec (p < 0.01). Minimal LV diastolic pressure and LV end-diastolic pressure (LVEDP) were significantly lowered after 50′ from 13 ± 4 to 10 ± 7 mm Hg (p < 0.05) and from 27 ± 7 to 20 ± 10 mm Hg (p < 0.01), respectively. Coronary blood flow rose progressively during the first 40′ but the increase failed to be significant at 50′. Coronary vascular resistance reciprocated these changes. Myocardial oxygen consumption remained unchanged over 50′. Noradrenaline, adrenaline and dopamine mean values also remained unchanged over 50′, thus demonstrating a lack of effect of M on the basal, elevated sympathetic tone. Mean plasma level of M rose progressively, achieving a therapeutic level after 30′. The analysis of LV volume, pressure and pressure-derived parameters during angiography showed an improved relaxation phase with an increase in peak filling rate from 290 ± 27 to 338 ± 55 ml sec. The constant of elastic chamber stiffness, measured by the simple elastic model, decreased but not significantly. Pressure-volume loops showed a downward shift in 10/14 pts, mainly because of a major reduction in LVEDP from 29 ± 10 to 20 ± 11 mm Hg (p < 0.001) while end-diastolic volume only slightly decreased.
Conclusion: improvement in parameters of LV diastolic relaxation and filling with changes in chamber distensibility following oral M, suggest that improved diastolic function may contribute to the beneficial effects of M on the failing heart.
During the last two years several investigators have demonstrated that the administration of milrinone in patients with congestive heart failure leads to an increased inotropism together with a vasodilation, in absence or with only slight changes in heart rate and aortic pressure (1, 7, 10, 16). Recently an improvement in diastolic left ventricular performance, occurring after intravenous milrinone, has been reported (14). In the present study we evaluated the effect of a single oral dose of milrinone on central hemodynamics and on systolic and diastolic mechanics in patients with congestive heart failure.
KeywordsFatigue Ischemia Dopamine Noradrenaline Cardiomyopathy
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- 4.Edelson J, Koss RF, Baker JF, Park GO (1983) High performance liquid chromatographic analysis of WIN 47.203 in plasma and urine. Intravenous pharmacokinetics in the dog. Chromatogr F276: 456–462Google Scholar
- 6.Gwethmey JK, De Feo TT, Morgan JP (1984) The effects of milrinone and 2H-imidazol-2-one, 4ethyl-1,3-didydro-5-(4-pyridimilcarbonil)-(MDL 19.205) on intracellular calcium transients in mammalian working myocardium. Fed Proc 43: 768 (abstr)Google Scholar
- 7.Jaski BE, Fifer MA, Wright RF, Braunwald E, Colucci WS (1985) Positive inotropic and vasodilator actions of milrinone in patients with severe congestive heart failure. Dose-response relationships and comparison to nitroprusside. J Clin Invest 75: 643–649Google Scholar
- 11.Meester GT, Bernard N, Zeelenberg C, Brower RW, Hugenholtz PG (1975) A computer system for real time analysis of cardiac catheterization data. Cathet Cardiovasc Diagno 1: 112 – 132Google Scholar
- 17.Slager CJ, Reiber JHC, Schuurbiers JCH, Meester GT (1978) Contouromat, a hardwired left ventricular angio processing system. Design and application. Comput Biomed Res 11: 491–502Google Scholar