Table 3.
Experimental studies of cardioprotection via post-ischaemic opioid receptor agonism
| Putative selectivity | Agent studied | Species, tissue | Primary outcome | Effect | Implicated effectors or targets | Study |
|---|---|---|---|---|---|---|
| Non-selective | Morphine | Rat, isolated heart | Infarct (TTC) | Improved | mKATP, KOR (DOR antagonist insensitive) | Chen et al., 2008 |
| Infarct (TTC) | Improved | NO/PKG, mPTP | Jang et al., 2008 | |||
| Infarct (TTC) | Improved | δ/δ1 receptor, KOR, mPTP | Kim et al., 2011 | |||
| DOR | DADLE (δ/δ1 receptor) | Rabbit, isolated heart | Infarct (TTC) | Improved | Akt, ERK1/2, EGFR | Förster et al., 2007 |
| Human, atrial trabeculae | Contractility | Improved | mPTP | Fuardo et al., 2013 | ||
| BW-373U86 | Rat, in situ heart | Infarct (TTC) | Improved | mKATP, sarcKATP | Gross et al., 2007a | |
| Rat, isolated heart | Infarct (TTC) | Improved | NO/PKG, mPTP | Jang et al., 2008 | ||
| SNC-121 | Mouse, in situ heart | Infarct (TTC) | Improved | ROS | Tsutsumi et al., 2007 | |
| KOR | U50,488H | Rat, in situ and mouse, isolated heart | Infarct (TTC) | Improved | PI3K, mKATP | Peart et al., 2008 |
| Rat, in situ heart | Infarct (TTC) | Improved | PI3K/Akt, eNOS | Tong et al., 2011 | ||
| MOR | Remifentanil | Rat, in situ heart | Infarct (TTC) | Improved | KOR, DOR | Wong et al., 2010bb |
| Sufentanil | Rat, in situ heart | Infarct (TTC) Apoptosis | Improved | PI3K/Akt, GSK3β, Bax/Bcl-2 | Wu et al., 2012a | |
| Infarct (TTC) | Improved | Cx43 | Wu et al., 2012b | |||
| MOR/DOR | Eribis peptide 94 | Pig, in situ heart | Infarct (TTC) | Improved | Karlsson et al., 2012 |
Shown are the effects of post-ischaemic opioid receptor agonists on outcomes from myocardial I–R in experimental animal models and ex vivo human tissue. Agonists were applied in the late stages of ischaemia prior to reperfusion (perconditioning) or during the reperfusion phase. Outcomes include infarction or apoptosis, and contractile recovery. Also shown are the receptors, signalling elements or effector molecules implicated in protection (where assessed). BW373U86, 4-[(R)-[(2S,5R)-2,5-dimethyl-4-prop-2-enylpiperazin-1-yl]-(3-hydroxyphenyl)methyl]-N,N-diethylbenzamide; Cx43, connexin-43; DADLE, [d-Ala2, d-Leu5] enkephalin; DAMGO, [D-Ala2, N-MePhe4, Gly-ol]-enkephalin; GSK3β, glycogen synthase kinase 3β; mKATP, mitochondrial KATP channel; sarcKATP, sarcolemmal KATP channel; SNC-121, 4-((aR)-a-((2S,5R)-4-Propyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl)-N,N-diethylbenzamide; TTC, 2,3,5-triphenyl-2H-tetrazolium chloride staining for infarction; U50,488H, [(trans)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]benzeneacetamide].