Desflurane-induced Preconditioning Alters Calcium-induced Mitochondrial Permeability Transition

Background: Recent investigations have focused on the pivotal role of the mitochondria in the underlying mechanisms volatile anesthetic-induced myocardial preconditioning. This study aimed at examining the effect of anesthetic preconditioning on mitochondrial permeability transition (MPT) pore opening.

Methods: Anesthetized open chest rabbits were randomized to one of four groups and underwent 10 min of ischemia, except for the sham 1 group (n = 12). Before this, they underwent a treatment period consisting of (1) no intervention (ischemic group; n = 12), (2) 30 min of desflurane inhalation (8.9% end-tidal concentration) followed by a 15-min washout period (desflurane group; n = 12), or (3) ischemic preconditioning (IPC group; n = 12). A second set of experiments was performed to evaluate the effect of a putative mitochondrial adenosine triphosphate-sensitive potassium channel antagonist, 5-hydroxydecanoate (5-HD). The animals underwent the same protocol as previously, plus pretreatment with 5 mg/kg 5-HD. They were randomized to one of five groups: the sham 2 group, receiving no 5-HD (n = 12); the sham 5-HD group (n = 12); the ischemic 5-HD group (n = 12), the desflurane 5-HD group (n = 12), and the IPC 5-HD group (n = 12). At the end of the protocol, the hearts were excised, and mitochondria were isolated. MPT pore opening was assessed by measuring the amount of calcium required to trigger a massive calcium release indicative of MPT pore opening.

Results: Desflurane and IPC group mitochondria needed a higher calcium load than ischemic group mitochondria (362 +/- 84, 372 +/- 74, and 268 +/- 110 mu]m calcium, respectively; P < 0.05) to induce MPT pore opening. The sham 1 and sham 2 groups needed a similar amount of calcium to trigger mitochondrial calcium release (472 +/- 70 and 458 +/- 90 mu]m calcium, respectively). 5-HD preadministration had no effect on sham animals (458 +/- 90 and 440 +/- 128 mu]m calcium without and with 5-HD, respectively) and ischemic group animals (268 +/- 110 and 292 +/- 102 mu]m calcium without and with 5-HD, respectively) but abolished the effects of desflurane on calcium-induced MPT pore opening (362 +/- 84 mu]m calcium without 5-HD vs. 238 +/- 96 mu]m calcium with 5-HD; P < 0.05) and IPC (372 +/- 74 mu]m calcium without 5-HD vs. 270 +/- 104 mu]m calcium with 5-HD; P < 0.05).