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

Abstract

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 μg/kg (LMPC), 3 μg/kg (MMPC) or 30 μg/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-ρ-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.

• Authors: J Ling Ling, G T C Wong, L Yao, Z Xia, M G Irwin
• Journal: Acta anaesthesiologica Scandinavica (Acta Anaesthesiol Scand) Vol. 54 Issue 9 Pg. 1097-104 (Oct 2010) ISSN: 1399-6576 [Electronic] England
• PMID: 20887411 (Publication Type: Journal Article)

Chemical References

• Analgesics, Opioid
• Receptors, Opioid
• Morphine

Topics

• Analgesics, Opioid (administration & dosage)
• Animals
• Injections, Spinal
• Ischemic Postconditioning (methods)
• Morphine (administration & dosage)
• Myocardial Infarction (drug therapy)
• Myocardial Reperfusion Injury (prevention & control)
• Rats
• Rats, Sprague-Dawley
• Receptors, Opioid (drug effects, physiology)