[Protective effects of a delta-opioid-receptor agonist and an oxygen radical scavenger on postischemic hearts].
OBJECTIVE
The cardioprotective effects of delta-opioid receptor agonists is mediated-at least in part-via oxygen radicals. Mannitol that is used in cardiac surgery because of its osmotic properties exerts its beneficial effects on stunned myocardium via scavenging hydroxyl radicals. The effects of a delta-opioid receptor agonist (D-Ala2-D-Leu5-Enkephalin [DADLE]), the radical scavenger mannitol and their combination on postischemic dysfunction in rabbit hearts were investigated.


METHODS
Isolated, blood-perfused rabbit hearts were subjected to a 20-min global, normothermic, no-flow ischemia that was followed by a 60-min reperfusion. Systolic and diastolic ventricular function as well as coronary blood flow (CBF) were assessed. The hearts were assigned to one of four groups: 1. placebo (n = 6); 2. DADLE (n = 8; 430 nM); 3. mannitol (n = 7; 8.6 mM); 4. DADLE + mannitol (n = 7).


RESULTS
Ischemic contracture in the DADLE and the mannitol group was significantly smaller compared with the placebo group. Contracture was smallest in the DADLE + mannitol group. The postischemic function in the placebo group was drastically reduced (p < 0.05), while it was best preserved in the DADLE + mannitol group. CBF and MVO(2) were changed similarly in all groups (n. s.). The external efficiency was significantly higher in the groups with DADLE and/or mannitol than in the placebo group. Both DADLE and mannitol exhibit cardioprotective properties. Combination of both substances exerts an additive, positive effect on the ischemic contracture. Noteworthy, the protective effects of DADLE during reperfusion were not antagonized by the oxygen radical scavenger mannitol. On the other hand, DADLE + mannitol did not augment the protective effects of the single substances during reperfusion, except for the isovolumic LVP(max).


CONCLUSIONS
Both substances improve the postischemic systolic and diastolic function and the relation between cardiac work and oxygen needed for this work. Thus, both substances offer promising properties in the clinic.
Schipke
Jochen D
JD
Forschungsgruppe Experimentelle Chirurgie, Universitätsklinikum Düsseldorf, Düsseldorf. schipke@med.uni-duesseldorf.de
Nickel
Frank
F
Gams
Emmeran
E
Sunderdiek
Ulrich
U
D000701:Analgesics, Opioid / Q000008:administration & dosage; D000818:Animals; D004338:Drug Combinations; D016308:Enkephalin, Leucine-2-Alanine / Q000008:administration & dosage*; D016166:Free Radical Scavengers / Q000008:administration & dosage; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D008353:Mannitol / Q000008:administration & dosage*; D009200:Myocardial Contraction / Q000187:drug effects; D017202:Myocardial Ischemia / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D015428:Myocardial Reperfusion Injury / Q000175:diagnosis / Q000209:etiology / Q000517:prevention & control*; D011817:Rabbits; D017382:Reactive Oxygen Species / Q000008:administration & dosage; D020127:Recovery of Function / Q000187:drug effects; D016896:Treatment Outcome
D000701:Analgesics, Opioid; D004338:Drug Combinations; D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D008353:Mannitol; D016308:Enkephalin, Leucine-2-Alanine