P131 | DO NATURAL HIBERNATION AND ISCHEMIC PRECONDITIONING ACT VIA SIMILAR PATHWAY? |
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| Hannover Medical School, Hannover, Germany1University of Michigan Medical Center, Ann Arbor, USA | |
Objective: The delta-opioid receptor agonist, D-Ala2-Leu5-enkephalin DADLE, which induces natural hibernation, has been demonstrated to improve organ preservation. On the other hand, delta-opioid receptors have been implicated to mediate cardioprotective effects of ischemic preconditioning. This study was designed to test the hypothesis that ischemic preconditioning and opioid receptor stimulation by DADLE act via similar pathway.
Methods: Isolated working rat hearts were subjected to 45 minutes of hypothermic global ischemia at 30° C followed by 25 minutes of normothermic reperfusion. Hearts from the rats pretreated with DADLE or the opioid receptor antagonist naloxone were preconditoned by one cycle of 5 minutes of normothermic global ischemia and subsequent reperfusion prior to prolonged ischemia. Untreated preconditioned or non-preconditioned rats served as control.
Results: Ischemic preconditioning and DADLE improved the recovery of aortic flow and reduced the creatine kinase (CK) leakage during reperfusion independently and significantly when compared to non-preconditioning. Pretreatment with DADLE prior to ischemic preconditioning significantly improved the recovery of aortic flow compared to DADLE alone and ischemic preconditioning alone. Naloxone counteracted the beneficial effects of ischemic preconditioning and DADLE.
| n | LVSP (%) | Aortic flow (%) | CK (IU/5 min/heart) | |
| non-PC | 8 | 85.6 ± 3.0 | 40.0 ± 1.5 | 0.80 ± 0.04 |
| ischemic PC | 8 | 93.0 ± 1.7 | 60.8 ± 1.5* | 0.57 ± 0.02* |
| DADLE | 8 | 89.8 ± 1.3 | 57.7 ± 1.4* | 0.58 ± 0.02* |
| DADLE + ischemic PC | 8 | 91.8 ± 1.8 | 68.6 ± 1.2# | 0.48 ± 0.04* |
| naloxone | 8 | 86.7 ± 2.7 | 39.5 ± 1.7 | 0.75 ± 0.08 |
| naloxone + ischemic PC | 8 | 87.9 ± 1.5 | 45.6 ± 2.4 | 0.61 ± 0.04 |
| DADLE + naloxone | 5 | 87.9 ± 1.1 | 40.1 ± 2.4§ | 0.70 ± 0.08 |
| DADLE + naloxone + | ||||
| ischemic PC | 5 | 88.4 ± 1.3 | 42.7 ± 2.2¶ | 0.68 ± 0.08 |
PC; preconditioning, LVSP; left ventricular systolic pressure, Data are expressed as mean ± SEM. LVSP and aortic flow in % of preischemic values. *p < 0.01 vs. non-PC, #p < 0.01 vs. DADLE alone and ischemic PC alone. p < 0.01 vs. ischemic PC, §p < 0.01 vs. DADLE, ¶p < 0.01 vs. DADLE + ischemic PC.
Conclusion: DADLE attenuates postischemic injury in isolated rat hearts and enhances protective effects of ischemic preconditioning. The data suggest that ischemic preconditioning and DADLE act via a similar pathway.
