Restoration of cardiac function following one-day cold perfusion of
isolated hearts with butanedione monoxime plus the katp channel
opener bimakalim.
Stowe, David F., Bernhard M. Graf, Satoshi Fujita, and Garrett J.
Gross.
Anesthesiology Research Laboratory, Departments of Anesthesiology,
Physiology, Pharmacology and Toxicology, Cardiovascular Research
Center, Medical College of Wisconsin, and Research Service, Veterans
Affairs Medical Center, Milwaukee, Wisconsin
APStracts 3:0158H, 1996.
Bimakalim (BIM), an opener of ATP-sensitive potassium (KATP) channels,
was given alone or with butanedione monoxime (BDM), a reversible
uncoupler of contractility, to protect myocardial function during one
day of hypothermia. Left ventricular pressure (LVP), coronary flow
(CF), % O2 extraction (% O2E), and cardiac efficiency (CE) were
measured in 96 isolated, perfused guinea pig hearts divided into 7
groups: Cold Control (no drugs); BDM; BIM; BDM+BIM; BDM+glibenclamide
(GLB, a blocker of KATP channels); BDM+BIM+GLB; and Time Control (6
hrs warm perfusion only). Drugs were given before, during, and
initially after 22 hrs of low CF at 3.8 [acute]iC. At hr 26 (cold
groups) or hr 4 (warm group) LVP (mm Hg, mean SEM) was similar for
Time Control (94 4) and BDM+BIM (92 4) groups, lower and equivalent
in the BDM (65 7) and BDM+BIM+GLB (64 7) groups but higher than in
the BIM group (46 3), and lowest in the Cold Control (30 8) group. In
addition, only in the BDM+BIM group was basal CF, % O2E, and CE
returned to values obtained in the Time Control group. Epinephrine
increased LVP to that of the Time Control (106 3) group only in the
BDM+BIM group (106 3) after hypothermia, and CF increases with
adenosine, 5-hydroxytryptamine, and nitroprusside were similar to
that of the time control group only in the BDM+BIM group after
hypothermia. All of the effects of BIM were reversed by GLB. These
results indicate that BIM, given with BDM, effectively preserves
myocardial function and metabolism as well as inotropic and
vasodilatory reserve during long-term hypothermic preservation as if
the one day hypothermic state had not been instituted. Because the
beneficial effects of BIM are blocked by GLB, the protective effect
of BIM likely results from maintained KATP channel opening. Treatment
with exogenous KATP openers may prove useful in preserving cardiac
function in the transplanted heart.
Received 23 October 1995; accepted in final form 28 March 1996.
APS Manuscript Number H986-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 23 April 96