Desflurane-Induced Cardioprotection Against Ischemia-Reperfusion Injury Depends On Timing

Objectives

The authors tested the hypothesis that desflurane-induced cardioprotection depends on the timing of application and whether desflurane-induced postconditioning is mediated by nitric oxide.

Design

A prospective randomized vehicle-controlled study.

Setting

A university research laboratory.

Subjects

New Zealand White rabbits (N = 56).

Interventions

Rabbits were instrumented and subjected to a 30-minute coronary artery occlusion (CAO) and 3 hours of reperfusion. Animals were randomized to 8 groups (n = 7) and received 0.0 or 1.0 minimum alveolar concentration desflurane for 30 minutes before CAO (PRE), during CAO (ISCH), after CAO (POST), before and after CAO (PRE + POST), or continuously for 90 minutes starting 30 minutes before CAO (PRE + ISCH + POST). In 2 separate experimental groups, the nitric oxide synthase inhibitor N-omega-nitro-L-arginine (L-NA) was administered before reperfusion in the presence or absence of desflurane. Data are mean ± standard deviation.

Results

Infarct size was 68% ± 14% in control experiments. Desflurane significantly (p < 0.05) reduced infarct size in the PRE (43% ± 9%) and POST groups (49% ± 12%) but not in the ISCH group (69% ± 9%). The PRE + ISCH + POST and PRE + POST groups produced similar reductions in infarct size to 47% ± 12% and 43% ± 9%, respectively. L-NA alone had no effect on infarct size (61% ± 9%) but blocked postconditioning completely (L-NA + POST, 68% ± 10%).

Conclusions

Desflurane induces pre- and postconditioning but does not confer cardioprotection during ischemia in rabbits. The combination of pre- and postconditioning or continuous application does not provide additional cardioprotection. Furthermore, desflurane-induced postconditioning is mediated by nitric oxide.

Key Words: cardioprotection, reperfusion injury, preconditioning, postconditioning, desflurane, volatile anesthetics, myocardial infarction, rabbit