Abstract 13127: Type 2 Diabetic Obese db/db Mice Are Refractory to Myocardial Ischemic Postconditioning Due to Deficiency of Leptin Receptors
Background: Since the first description of ischemic postconditioning (PostC) in dog model, this clinically relevant cardioprotective modality has been confirmed by numerous investigators in many species including humans. However, majority of the studies on PostC were done in healthy subjects. It remains unknown if PostC can still protect heart in the individuals suffering from Type 2 diabetes, a condition which is rapidly growing in the World. To answer this important question, we investigated the efficacy of PostC in the membrane-bound leptin receptor deficient db/db mice, which possess many characteristics of Type 2 diabetes including obesity, hyperglycemia and hyperleptinemia.
Methods & Results: Male 10 to 12-week-old C57BL/6J wild-type (WT) and db/db mice were anesthetized with pentobarbital, intubated and mechanically ventilated. Following left thoracotomy, left coronary artery was occluded for 30 min followed by 24 hrs of reperfusion (Control groups; n=6 each). For PostC groups, the hearts underwent 6 cycles of 10 sec of reperfusion and 10 sec of re-occlusion at the onset of reperfusion (n=6 each). The mice were sacrificed 24 hrs later for infarct size measurement with TTC staining. The blood glucose levels were significantly higher in db/db as compared with WT mice (Fig. 1; P<0.01). The body weight (Mean±SE) was 29.5±1.0, 30.1±0.3, 50.5±0.7, 51.3±0.9 g for WT, WT+PostC, db/db and db/db+PostC, respectively (P<0.01 WT vs. db/db). PostC significantly reduced infarct size in WT group (P<0.05; Fig. 2). In contrast, PostC failed to limit infarct size in db/db mice. Moreover, infarct size was significantly higher in db/db as compared with WT mice, The area at risk was similar among all groups,
Conclusions: For the first time, we show that PostC fails to protect Type 2 diabetic mice against ischemia-reperfusion injury possibly due to the deficiency of leptin receptors. These results raise concerns of potential utility of PostC in cardioprotection in diabetic patients.
- © 2010 by American Heart Association, Inc.