MILRINONE, A CYCLIC AMP-PHOSPHODIESTERASE INHIBITOR, HAS DIFFERENTIAL-EFFECTS ON REGIONAL MYOCARDIAL WORK AND OXYGEN-CONSUMPTION IN EXPERIMENTAL LEFT-VENTRICULAR HYPERTROPHY
Wc. Chiu et al., MILRINONE, A CYCLIC AMP-PHOSPHODIESTERASE INHIBITOR, HAS DIFFERENTIAL-EFFECTS ON REGIONAL MYOCARDIAL WORK AND OXYGEN-CONSUMPTION IN EXPERIMENTAL LEFT-VENTRICULAR HYPERTROPHY, Cardiovascular Research, 28(9), 1994, pp. 1360-1365
Objective: The aim was to test the hypothesis that local myocardial wo
rk and O-2, consumption would respond differentially to milrinone, a s
elective cyclic AMP-phosphodiesterase inhibitor, in left ventricular h
ypertrophy due to differences in myocardial cyclic AMP-phosphodiestera
se activity. Methods: The effect of milrinone on regional segment work
and regional O-2 consumption was measured in 12 open chest anaestheti
sed dogs with left ventricular hypertrophy induced by valvular aortic
stenosis and in 10 age matched control dogs. Regional myocardial work
was calculated as the integrated product of instantaneous force develo
pment (miniature transducer) and segment shortening (sonomicrometer).
Regional O-2 consumption was calculated from coronary blood flow (radi
olabelled microspheres) and O-2, saturations in small regional vessels
(microspectrophotometry). Low Km phosphodiesterase activity was assay
ed by measuring the hydrolysis of radiolabelled cyclic AMP. Results: M
ilrinone increased left ventricular dP/dt(max) by approximately 60-70%
in both control [2808(SEM 314) to 4584(660) mm Hg.s(-1)] and left ven
tricular hypertrophy [3279(258) to 5589(470) mm Hg.s(-1)]. Regional wo
rk increased significantly in control [612(88) to 955(101) g.mm.min(-1
)], while the increase was not significant in left ventricular hypertr
ophy [859(139) to 974(172) g.mm.min(-1). Regional O-2 Consumption incr
eased significantly with milrinone in left ventricular hypertrophy [8.
1(1.2) to 13.1(2.4) ml O-2.min(-1).100 g(-1)], but the increase was no
t significant in control [6.9(1.2) to 7.4(1.0) ml O-2.min(-1).100 g(-1
). Myocardial stiffness during ejection was increased by milrinone to
a significantly greater extent in animals with left ventricular hypert
rophy. These effects were not related to differences in cyclic AMP-pho
sphodiesterase activity between control hearts and hearts with left ve
ntricular hypertrophy [393(45) v 402(36) pmol.mg protein(-1).min(-1)].
Conclusions: Differences between the hypertrophied and normal canine
myocardium in response to milrinone are either due to altered levels o
f cyclic AMP production in left ventricular hypertrophy, to effects of
milrinone that are unrelated to cyclic AMP-phosphodiesterase inhibiti
on, or to other differences in hypertrophied hearts. The greater stiff
ness of the myocardium in left ventricular hypertrophy may require a g
reater energy expenditure to increase the amount of work it performs.