The ca2+ sensitizer org 30029 reverses acidosis- and bdm-induced contractile depression in canine myocardium. Watanabe, Akira, Hitonobu Tomoike, and Masao Endoh. Department of Pharmacology and The First Department of Internal Medicine, Yamagata University School of Medicine, Yamagata 990-23, Japan
APStracts 3:0220H, 1996.
Effects of the Ca2+ sensitizer, N-hydroxy-5,6-dimethoxy -benzothiophene-2-carboximidamide hydrochloride (Org 30029), on the myocardial contractile depression induced by acidosis and 2,3 -butanedione monoxime (BDM) were investigated in aequorin-loaded canine ventricular myocardium. The peak Ca2+ transient-peak force relation during administration of Org 30029 (10-4 M-10-3 M) was shifted to the left and upwards, as compared with the relation for elevation of the extracellular Ca2+ concentration ([Ca2+]o) (2.5 mM -12.5 mM). Acidosis (pH 6.6) depressed the force with a small increase in the peak Ca2+ transient. BDM (3 mM) depressed the force with no change in the peak and duration of the Ca2+ transient, indicating that BDM may inhibit selectively the cross-bridge interaction. During acidosis or in the presence of BDM, elevation of [Ca2+]o increased the peak Ca2+ transient to the same extent as that in the control but the force was inhibited. By contrast, Org 30029 increased the force to a level equivalent to the control with a slight change in the peak Ca2+ transient. In addition, during acidosis, Org 30029 (10-3 M) increased the force in association with a slight decrease in the peak Ca2+ transient. Thus, Org 30029 can reverse the myocardial contractile depression induced by a decrease in the Ca2+ sensitivity of myofilaments, as occurs in pathophysiological situations, such as acidosis in cardiac ischemia. Org 30029 may exert the Ca2+ sensitizing effect by an increase in the affinity of troponin C for Ca2+ and by a direct action on the cross-bridge interaction. 

Received 13 February 1996; accepted in final form 6 May 1996.
APS Manuscript Number H144-6.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 5 June 96