Differential effects of emd 53998 on calcium-pressure relationship
in normal and ischemic guinea pig heart.
Ishisu, Ryoichi, Yuji Abe, Katsuya Onishi, Kiyotsugu Sekioka, and
Takeshi Nakano.
First Department of Internal Medicine, Mie University School of
Medicine, Tsu 514, Japan
APStracts 3:0046H, 1996.
We investigated the effects of EMD 53998 and digoxin on Ca2+
transients and left ventricular (LV) function in indo-1-loaded
Langendorff guinea pig hearts. EMD 53998 (10-9-10-5 M) and digoxin
(10-10-10-6 M) increased +dP/dt and Ca2+ transients in normal hearts.
The relative increase in Ca2+ transients by EMD 53398 was similar to
digoxin. At 10-5 M EMD 53998 increased LV end-diastolic pressure. Low
flow ischemia decreased +dP/dt by 50%, while indo-1 ratio increased
by 10-25%. EMD 53998 (10-9-10-6 M) effectively restored the depressed
+dP/dt with a little effect on indo-1 ratio, but at 10-5 M it
markedly elevated LV end-diastolic pressure, and beneficial effect on
contractile dysfunction disappeared. Digoxin (10-10-10-7 M) failed to
improve LV function, but at 10-6 M it restored contractile
dysfunction with a large increase in indo-1 ratio. The relation
between indo-1 ratio and +dP/dt clearly showed that EMD 53998
restored contractile dysfunction by Ca2+ sensitization. These
findings suggest that Ca2+ sensitization by EMD 53998 is an
advantageous approach for ischemic contractile failure, but impairs
diastolic function.
Received 7 July 1995; accepted in final form 5 January 1996.
APS Manuscript Number H626-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 8 February 96