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 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.
Ling Ling
J
J
Department of Anaesthesiology, University of Hong Kong, Hong Kong.
Wong
G T C
GT
Yao
L
L
Xia
Z
Z
Irwin
M G
MG
D000701:Analgesics, Opioid / Q000008:administration & dosage*; D000818:Animals; D007278:Injections, Spinal; D057775:Ischemic Postconditioning / Q000379:methods*; D009020:Morphine / Q000008:administration & dosage*; D009203:Myocardial Infarction / Q000188:drug therapy; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011957:Receptors, Opioid / Q000187:drug effects / Q000502:physiology*
D000701:Analgesics, Opioid; D011957:Receptors, Opioid; D009020:Morphine