(Circulation. 1995;92:3094-3104.)
© 1995 American Heart Association, Inc.
Articles |
Effects of EMD 57033 on Contraction and Relaxation in Isolated Rabbit Hearts
From the Cardiology Unit, College of Medicine, University of Vermont, Burlington.
Correspondence to Martin M. LeWinter, MD, Cardiology Unit, McClure 1, Fletcher Allen Health Care, MCHV Campus, Burlington, VT 05401.
Background Ca2+ sensitizers are reported to enhance contractility with modest effects on energy utilization. In the present study we assessed the effects of the relatively "pure" Ca2+ sensitizer EMD 57033 on mechanical performance and energy consumption in the beating heart.
Methods and Results In 10 isolated, red blood cell–perfused
rabbit hearts the effects of EMD 57033 (5.0 to 5.8 µmol/L) on left
ventricular (LV) pressure and O2 consumption
(
O2) were examined at heart
rates of 100
and 150 beats per minute (bpm) and perfusate
[Ca2+]
([Ca2+]o) of 2.5 and 1.0 mmol/L
(isovolumic contractions). LV developed pressure and maximum dP/dt
increased, but less so at 150 bpm or 1.0 mmol/L
[Ca2+]o. End-diastolic
pressure also increased, more so at 150 bpm or 1.0 mmol/L
[Ca2+]o. EMD 57033 decreased time to
peak isovolumic pressure (Tmax) and prolonged time
to 50% pressure decline (T1/2). These changes were greater
at slower heart rate or lower
[Ca2+]o. The magnitude of increased
O2 with EMD 57033 was
greater at 100 bpm
than 150 bpm but unaffected by
[Ca2+]o. We then investigated the
influence of ejection on the response to EMD 57033 (n=7). The increase
in developed pressure with EMD 57033 was greater for ejecting than
isovolumic beats (25.5±10.2 versus 14.7±7.5 mm Hg at 100 bpm,
P<.01), while the increase in end-diastolic
pressure was less (P=NS). The increase in
O2 was significantly
greater for
ejecting than isovolumic beats (0.027±0.013 versus 0.020±0.009
mL
O2/beat per 100 g at 100 bpm,
P<.01).
Conclusions EMD 57033 enhances contractility and prolongs relaxation. Its effects are modulated by heart rate, [Ca2+]o, and contraction mode, with positive inotropic effects being more prominent for ejecting beats.
Key Words: calcium • contractility
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