No involvement of endogenous adenosine or atp-dependent potassium channels
in regional short-term myocardial hibernation in swine.
Schulz, Rainer, M. D., Jochen Rose, Heiner Post, Gerd Heusch, M. D.
Abteilung f[umlaut]ur Pathophysiologie, Zentrum f[umlaut]ur Innere Medizin
des Universit[umlaut]atsklinikums Essen
APStracts 2:0006H, 1995.
Short-term hibernating myocardium is characterized by reduced contractile
function during persistent ischemia, the recovery of metabolism over time, a
recruitable inotropic reserve, and the lack of necrosis. The mechanisms
underlying myocardial hibernation are unclear. The present study addressed
the role of endogenous adenosine and that of activation of ATP-dependent
potassium channels. In 22 enflurane-anesthetized swine, coronary inflow was
reduced to decrease regional myocardial work (W, sonomicrometry) by 60-70% at
5 minutes ischemia; this flow reduction was previously shown to be compatible
with the development of myocardial hibernation. Systemic hemodynamics, W,
subendocardial blood flow (microspheres) and the myocardial CP content
(biopsies, [mu]mol/g wet weight) were measured under control conditions and
during 90 minutes ischemia, with an intracoronary dobutamine infusion during
the last 5 minutes ischemia. The impact of endogenous adenosine was
eliminated by infusion of intracoronary adenosine deaminase (ADA), that of
activation of ATP-dependent potassium channels by glibenclamide (G). CP
content recovered in the placebo-swine (n=8, 3.8+/-1.9 to 5.8+/-2.0) as well as
in swine receiving ADA (n=7, 4.1+/-1.2 to 6.0+/-1.7) or G (n=7, 2.8+/-1.3 to
6.7+/-1.6) when ischemia was prolonged from 5 to 85 minutes. At the end of the
90 minutes ischemia, W increased during intracoronary dobutamine in all three
groups to a comparable extent, and myocardial necrosis was absent in all
three groups of swine. Conclusion: Neither endogenous adenosine nor
activation of ATP-dependent potassium channels are involved in the
development of short-term myocardial hibernation in anesthetized swine.
Received 10 November 1994; accepted in final form 6 January 1995.
APS Manuscript Number H1004-4.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 24 February 1995.