Fasting, lactate, and insulin improve ischemia tolerance in rat
heart: a comparison with ischemic preconditioning.
Doenst, Torsten, Patrick H. Guthrie, J[diaeresis]org-Michael
Chemnitius, Ronald Zech, and Heinrich Taegtmeyer.
Department of Internal Medicine, Division of Cardiology, University
of Texas - Houston Medical School, Houston, Texas 77030 and Zentrum
Innere Medizin and Zentrum Biochemie, Georg-August
-Universit[umlaut]at G[diaeresis]ottingen, 37075 G[diaeresis]ottingen,
Germany
APStracts 2:0456H, 1995.
We tested the hypothesis that improved ischemia tolerance in an
isolated working rat heart preparation can be achieved by
interventions other than ischemic preconditioning. Hearts were
perfused at near physiological workload with bicarbonate buffer
containing glucose (10 mM). A preischemic period of 25 min was
followed by 15 min of global ischemia and 30 min of reperfusion under
preischemic conditions. Hearts came from either fed or fasted animals
(groups 1 and 2). In group 3 lactate (10mM) and insulin (10 mU/ml)
were added to the perfusate of fasted animals. In group 4 hearts from
fed animals were perfused with glucose (10 mM) and were ischemically
preconditioned by one cycle of ischemia between 10 min and 15 min of
the preischemic perfusion. Cardiac power and glucose uptake were
measured continuously to assess functional and metabolic recovery. In
addition, we measured the time to return of aortic flow. Glucose
metabolites and the ratio of latent to free citrate synthase activity
(citrate synthase ratio, a marker for the structural integrity of
mitochondria) were determined at selected time points. Groups 2, 3,
and 4 recovered significantly faster than group 1, while recovery of
power showed an improvement in groups 3 and 4 only. In addition,
there was an early increase in glucose uptake during reperfusion in
these two groups suggesting an early need for glucose substrate.
Glycogen levels decreased with ischemia in all groups, and returned
to preischemic levels in groups 2, 3, and 4. The citrate synthase
ratio was low in the control group, and preserved in the groups
showing improved functional recovery. We conclude that metabolic
interventions may be as effective as ischemic preconditioning in
protecting the heart from ischemic injury.
Received 18 May 1995; accepted in final form 26 September 1995.
APS Manuscript Number H468-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 6 November 95