Fentanyl and myocardial protection: is there a preconditioning mechanism?

Introduction

Ischaemic preconditioning (IPC) was first reported by Murry and colleagues . Other triggers of preconditioning have subsequently been identified and there is now substantial evidence for involvement of the opioid receptor in preconditioning of rat hearts . Kato and Foex demonstrated that fentanyl, given as a pre-treatment and during reperfusion, improved postischaemic recovery of function, and suggested that a preconditioning mechanism may be involved. In this study, we set out to examine whether fentanyl acts to induce a preconditioning protection or whether it influences ischaemia-reperfusion effects.

Methods

Isolated rat hearts were Langendorff-perfused with Krebs Henseleit bicarbonate buffer (KHB) and function (left ventricular developed pressure: LVDP) measured with a fluid-filled LV balloon during a 15 min stabilisation period. Hearts (n = at least six per group) were then randomly assigned to one of five treatment groups and then subjected to 25 min global 37°C ischaemia followed by 60 min reperfusion (when recovery of function, expressed as percent of pre-ischaemic function, was measured). The five groups were: (a)Control: 30 min additional KHB perfusion, (b)Ischaemic preconditioning (IPC); three episodes of 5 min global ischaemia and 5 min reperfusion, (c)Fentanyl preconditioning (FPC); three episodes of 5 min KHB with 470 nmol/l fentanyl and 5 min KHB reperfusion, (d)Fentanyl pretreatment and reperfusion (FPT); 15 min KHB alone and 15 min KHB with 470 nmol/l fentanyl, (e)Fentanyl reperfusion (FREP); KHB reperfusion with 470 nmol/l fentanyl. Differences between groups were assessed by ANOVA and Dunnett's t-test (for multiple comparisons); P < 0.05 was considered significant.

Results

At the end of 60 min reperfusion, recovery of LVDP was 31 ± 3.5%, 52 ± 2.8%*, 31 ± 3.4%, 47 ± 1.9%* and 46 ± 3.8%* for groups (a)-(e) respectively [*P < 0.05 compared to group (a)].

Conclusions

We were unable to demonstrate that fentanyl, at the concentration used in this study, exerted a myocardial preconditioning protection. However, when added during reperfusion, fentanyl was beneficial and this appeared unrelated to any antiischaemic effect induced by pretreatment. The mechanism of action for this effect is currently unknown.