Circulation, Vol 84, 2559-2567, Copyright © 1991 by American Heart Association
DA Schwinn, BJ Leone, DR Spahn, LC Chesnut, SO Page, RL McRae and SB Liggett
BACKGROUND. Cardiopulmonary bypass (CPB), a process routinely used during
cardiac surgery, is a potent stimulant to the release of endogenous
catecholamines. Hence, we tested the hypothesis that CPB results in
myocardial beta-adrenergic receptor (beta AR) desensitization. METHODS AND
RESULTS. We obtained canine transmyocardial left ventricular biopsies
before, during (155 minutes), and after CPB (pre-CPB, CPB, and post-CPB,
respectively) and determined beta AR density, proportion of beta 1AR to
beta 2AR, and beta AR coupling capacity to adenylyl cyclase. Beta AR
density was stable at 112 +/- 14 fmol/mg (pre-CPB) and 103 +/- 9 fmol/mg
(CPB) but decreased post-CPB to 84 +/- 7 fmol/mg. The ratio of beta 1AR to
beta 2AR (determined by two-site fit for [125I]-iodocyanopindolol
competition binding with the beta 1AR selective antagonist ICI89.406)
remained constant throughout (60 +/- 3: 40 +/- 3 pre-CPB, 55 +/- 3: 44 +/-
3 CPB, and 61 +/- 2: 39 +/- 2 post-CPB), revealing that both beta 1AR and
beta 2AR subtypes were downregulated. A different pattern was noted in the
functional properties of these receptors during CPB. Decreased maximal
isoproterenol-stimulated adenylyl cyclase activity (252 +/- 14 to 216 +/-
12 pmol/30 min/mg), submaximal isoproterenol-stimulated adenylyl cyclase
activity (183 +/- 10 to 157 +/- 11 pmol/30 min/mg), and zinterol-stimulated
adenylyl cyclase activity (187 +/- 11 to 159 +/- 11 pmol/30 min/mg, a
measure of beta 2AR subtype activation) were noted during CPB, at the time
when weaning from CPB takes place. However, this desensitized pattern was
found to be completely reversed by 30 minutes post-CPB, with adenylyl
cyclase activities returning to pre-CPB levels or slightly higher. Control
dogs that did not receive CPB showed no change in beta AR density or
adenylyl cyclase activity. CONCLUSIONS. These data suggest that myocardial
beta AR desensitization does occur during CPB in healthy, nonischemic
canine myocardium and that this pattern is reversed 30 minutes after
discontinuation of CPB. In addition, a slower process of beta AR
downregulation persists after discontinuation of CPB. Because successful
weaning from CPB is a critical process during myocardial surgery, these
findings have potentially important implications in the management of such
patients.
ARTICLES
Desensitization of myocardial beta-adrenergic receptors during cardiopulmonary bypass. Evidence for early uncoupling and late downregulation
Department of Anesthesiology, Duke University Medical Center, Durham, N.C.
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