Remote pharmacological post-conditioning by intrathecal morphine: cardiac protection from spinal opioid receptor activation

Background Intrathecal morphine pre-conditioning attenuates cardiac ischemia-reperfusion injury via activation of central opioid receptors. We hypothesized that intrathecal morphine also post-conditions the myocardium in the rat. Methods Intrathecal morphine at 0.3 mu g/kg (LMPC), 3 mu g/kg (MMPC) or 30 mu g/kg (HMPC) was administered for 5 min before 120-min reperfusion following 30-min ischemia. Infarct size as a percentage of area at risk (IS/AAR) was determined using triphenyltetrazolium staining. MMPC was repeated following the intrathecal administration of nor BNI, NTD, CTOP, or naloxone methiodide (NM), kappa, delta, mu and non-specific opioid receptor antagonists, respectively. The role of peripheral opioid, adenosine and calcitonin gene-related peptide (CGRP) receptors was examined by the intravenous administration of NM, 8--sulfophenyl theophylline (8-SPT) and human CGRP fragment (CGRP(8-37)), respectively. Results Morphine post-conditioning at all three doses was cardioprotective (IS/AAR of LMPC=37 +/- 4%, MMPC=35 +/- 5%, HMPC=32 +/- 4%, control=50 +/- 5%, P < 0.01). The prior administration of opioid receptor antagonists intrathecally, as well as intravenous 8-SPT and CGRP(8-37) receptor antagonists, abolished this effect (nor BNI+MMPC=47 +/- 7%, NTD+MMPC=49 +/- 7%, CTOP+MMPC=45 +/- 9%, NM+MMPC=47 +/- 6% 8-SPT+MPC=46 +/- 5% & CGRP(8-37)+MPC=53 +/- 6%, P=0.63). However, the intravenous administration of NM did not prevent the protective effect (34 +/- 4%, P < 0.01). Conclusions Intrathecal morphine administration can induce pharmacological cardiac post-conditioning as it involves opioid receptor centrally but non-opioid receptors peripherally.