Desflurane-induced postconditioning is mediated by beta-adrenergic signaling: role of beta 1- and beta 2-adrenergic receptors, protein kinase A, and calcium/calmodulin-dependent protein kinase II.
BACKGROUND
Anesthetic preconditioning is mediated by beta-adrenergic signaling. This study was designed to elucidate the role of beta-adrenergic signaling in desflurane-induced postconditioning.


METHODS
Pentobarbital-anesthetized New Zealand White rabbits were subjected to 30 min of coronary artery occlusion followed by 3 h of reperfusion and were randomly assigned to receive vehicle (control), 1.0 minimum alveolar concentration of desflurane, esmolol (30 mg x kg(-1) x h(-1)) for the initial 30 min of reperfusion or throughout reperfusion, the beta2-adrenergic receptor blocker ICI 118,551 (0.2 mg/kg), the protein kinase A inhibitor H-89 (250 microg/kg), or the calcium/calmodulin-dependent protein kinase II inhibitor KN-93 (300 microg/kg) in the presence or absence of desflurane. Protein expression of protein kinase B, calcium/calmodulin-dependent protein kinase II, and phospholamban was measured by Western immunoblotting. Myocardial infarct size was assessed by triphenyltetrazolium staining.


RESULTS
Infarct size was 57 +/- 5% in control. Desflurane postconditioning reduced infarct size to 36 +/- 5%. Esmolol given during the initial 30 min of reperfusion had no effect on infarct size (54 +/- 4%) but blocked desflurane-induced postconditioning (58 +/- 5%), whereas esmolol administered throughout reperfusion reduced infarct size in the absence or presence of desflurane to 42 +/- 6% and 41 +/- 7%, respectively. ICI 118,551 and KN-93 did not affect infarct size (62 +/- 4% and 62 +/- 6%, respectively) but abolished desflurane-induced postconditioning (57 +/- 5% and 64 +/- 3%, respectively). H-89 decreased infarct size in the absence (36 +/- 5%) or presence (33 +/- 5%) of desflurane.


CONCLUSIONS
Desflurane-induced postconditioning is mediated by beta-adrenergic signaling. However, beta-adrenergic signaling displays a differential role in cardioprotection during reperfusion.
Lange
Markus
M
Department of Anesthesiology and Critical Care, University of Würzburg, Germany. lange_m@klinik.uni-wuerzburg.de
Redel
Andreas
A
Lotz
Christopher
C
Smul
Thorsten M
TM
Blomeyer
Christoph
C
Frank
Anja
A
Stumpner
Jan
J
Roewer
Norbert
N
Kehl
Franz
F
D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000502:physiology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology*; D000077335:Desflurane; D007530:Isoflurane / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D009203:Myocardial Infarction / Q000201:enzymology / Q000503:physiopathology / Q000517:prevention & control; D011817:Rabbits; D018342:Receptors, Adrenergic, beta-1 / Q000502:physiology*; D018343:Receptors, Adrenergic, beta-2 / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors
D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2; D000077335:Desflurane; D007530:Isoflurane; D017868:Cyclic AMP-Dependent Protein Kinases; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2