Abstract
BACKGROUND: Anesthetic and ischemic preconditioning share similar
signal transduction pathways. The authors tested the hypothesis that
the beta1-adrenergic signal transduction pathway mediates anesthetic
and ischemic preconditioning in vivo. METHODS: Pentobarbital-anesthetized
(30 mg/kg) rabbits (n = 96) were instrumented for measurement of
systemic hemodynamics and subjected to 30 min of coronary artery
occlusion and 3 h of reperfusion. Sixty minutes before occlusion,
vehicle (control), 1.0 minimum alveolar concentration desflurane,
or sevoflurane, and esmolol (30.0 mg x kg(-1) x h(-1)) were administered
for 30 min, respectively. Administration of a single 5-min cycle
of ischemic preconditioning was instituted 35 min before coronary
artery occlusion. In separate groups, the selective blocker esmolol
or the protein kinase A inhibitor H-89 (250 microg/kg) was given
alone and in combination with desflurane, sevoflurane, and ischemic
preconditioning. RESULTS: Baseline hemodynamics and area at risk
were not significantly different between groups. Myocardial infarct
size (triphenyltetrazolium staining) as a percentage of area at risk
was 61 +/- 4% in control. Desflurane, sevoflurane, and ischemic preconditioning
reduced infarct size to 34 +/- 2, 36 +/- 5, and 23 +/- 3%, respectively.
Esmolol did not alter myocardial infarct size (65 +/- 5%) but abolished
the protective effects of desflurane and sevoflurane (57 +/- 4 and
52 +/- 4%, respectively) and attenuated ischemic preconditioning
(40 +/- 4%). H-89 did not alter infarct size (60 +/- 4%) but abolished
preconditioning by desflurane (57 +/- 5%) and sevoflurane (61 +/-
1%). Ischemic preconditioning (24 +/- 7%) was not affected by H-89.
CONCLUSIONS: The results demonstrate that anesthetic preconditioning
is mediated by the beta1-adrenergic pathway, whereas this pathway
is not essential for ischemic preconditioning. These results indicate
important differences in the mechanisms of anesthetic and ischemic
preconditioning.
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