Ischemic preconditioning in human and rat ventricle.
Cleveland, Joseph C., Mary M. Wollmering, Daniel R. Meldrum, Robert T.
Rowland, Thomas F. Rehring, Brett C. Sheridan, Alden H. Harken,
Anirban Banerjee.
Department of Surgery, University of Colorado Health Sciences
Center, Denver, Colorado
APStracts 3:0178H, 1996.
The signal transduction of ischemic preconditioning involves
activation of endogenous receptor based systems - including [alpha]1
-adrenoceptors and adenosine receptors. While preconditioning protects
against ischemia-reperfusion injury - it is unknown if this
protective strategy might be useful clinically. Further, human atrium
has been successfully preconditioned, but it is unknown whether human
ventricle can be functionally protected against hypoxia
-reoxygenation. To study these questions, isolated rat ventricle and
human ventricular trabeculae were suspended in an organ bath and
subjected to 30 minutes hypoxia and 60 minutes reoxygenation. In the
rat ventricle, preconditioning was induced by 5 minutes of rapid
pacing at 3 Hz., in hypoxic buffer without glucose (simulated
ischemia); [alpha]1-adrenoceptor stimulation (phenylephrine); or
adenosine receptor stimulation (adenosine). In the human trabeculae,
the effects of preceding simulated ischemia, [alpha]1-adrenoceptor
and adenosine receptor stimulation were examined against H/R. In the
rat, pretreatment with simulated ischemia, [alpha]1-adrenoceptor and
adenosine receptor stimulation improved recovery of developed tension
(56 +/- 3%, 56 +/-4%, 58 +/- 2%, respectively) compared to control
trabeculae (25 +/- 2%) after H/R (p<0.05). In human trabeculae,
simulated ischemic pc, [alpha]1-adrenoceptor and adenosine receptor
stimulation augmented recovery of developed tension (65 +/- 5%, 59
+/- 6%, 60 +/- 3%, respectively) compared to control (29 +/- 2%)
after H/R (p<0.05). We conclude that functional cardioadaptation
(preconditioning) against hypoxia-reoxygenation injury in rat and
human myocardium exists, and that both [alpha]1-adrenergic and
adenosine receptor signaling participate in conferring this
protection.
Received 7 December 1995; accepted in final form 8 April 1996.
APS Manuscript Number H1136-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 1 May 96