Desflurane-Induced Preconditioning Has a Threshold That Is Lowered by Repetitive Application and Is Mediated by β₂-Adrenergic Receptors

Objective

An optimal administration protocol to induce a maximal effect of anesthetic preconditioning has not been evaluated to date. In this study, desflurane preconditioning was characterized with respect to its threshold, dose dependency, and continuous versus repetitive application. Furthermore, the role of β₂-adrenergic receptors in anesthetic preconditioning was tested.

Design

A randomized controlled study.

Setting

Laboratory study in a University hospital.

Subjects

New Zealand white rabbits in vivo.

Interventions

Systemic hemodynamics were continuously measured. Rabbits were subjected to 30 minutes of coronary artery occlusion and 3 hours of reperfusion. Animals received desflurane continuously for 30 minutes at 0.5, 1.0, or 1.5; desflurane for 90 minutes at 0.5 or 1.5 MAC; or repetitively for three 10-minute periods at 0.5, 1.0, or 1.5 MAC before coronary occlusion. The β₂-adrenergic receptor blocker ICI 118,551 (0.2 mg/kg) or saline placebo was given in the absence or presence of 1.0 MAC desflurane. Myocardial infarct size was measured with triphenyltetrazolium staining.

Measurements and Main Results

Myocardial infarct size was 61% ± 5% in control experiments. Desflurane, administered continuously at 0.5 MAC for 30 minutes (52% ± 4%) or 90 minutes (56% ± 8%) had no effect, whereas 0.5 MAC of desflurane given repetitively reduced infarct size to 36% ± 7%. Desflurane administered continuously for 30 minutes at 1.0 or 1.5 MAC reduced infarct size to 35% ± 5% and 39% ± 4%, respectively. Repetitive application at 1.0 MAC (37% ± 6%) or 1.5 MAC (29% ± 4%) and continuous administration of 1.5 MAC for 90 minutes (32% ± 6%) did not result in further infarct size reduction. ICI 118,551 did not affect infarct size (53% ± 2%) but abolished desflurane preconditioning (51% ± 5%).

Conclusion

β₂-Adrenergic receptors mediate desflurane-induced preconditioning. Desflurane-induced preconditioning has a threshold that can be lowered by repetitive administration.

Key Words: desflurane, preconditioning, cardioprotection, β-adrenergic receptors, infarct size