Abstract 20030: Reperfusion Therapy With Rapamycin Prevents Myocardial Injury in Type 2 Diabetic Rabbits
Background: A sustained hyperactive mammalian target of rapamycin (mTOR) leads to diabetic complication with cardiovascular disease through stimulation of oxidative stress and inflammatory responses, which cause myocardial reperfusion injury following ischemia. Therefore, we examined the effect of mTOR inhibition with rapamycin (RAPA) at reperfusion on reduction of myocardial infarction (MI) in a conscious type 2 diabetic (T2D) rabbit model of MI.
Methods and Results: The New Zealand white male rabbits (2.2-2.5 kg, 3-4 month old) were randomly assigned to the control group (n=10) fed with the normal chow. To induce T2D, another group (n=10) was fed with high fat diet (HFD) consisting of the standard rabbit chow with an additional 15% fat (10% corn oil and 5% lard) for a period of 25 weeks. Body weight and blood glucose levels were monitored. Post-heparin plasma was collected from rabbits to measure triglycerides, total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL, vLDL) using Colorimetric kit (BioVision CA). Subsequently, balloon occluders were implanted and 7 days later, these rabbits were subjected to a 45 min ischemia and 3 days of reperfusion. RAPA (0.25 mg/kg, i.v.) or DMSO (5% in saline, as vehicle) was infused 5 min before reperfusion. Body weights and glucose levels (n=10) were increased in HFD-fed rabbits (Figure A, B). Total cholesterol and LDL/vLDL were also increased, while HDL was reduced following HFD-fed (Figure C). T2D was further confirmed by impaired glucose tolerance in HFD-fed rabbits (Figure D). RAPA reduced infarct size in HFD-fed rabbits following I/R (Figure E). Risk-areas were not different between groups (Figure F).
Conclusion: Rapamycin is highly effective in attenuation of reperfusion injury in a conscious rabbit model of T2D. Thus novel mTOR inhibitor(s) could provide potentially new options for treatment of reperfusion injury in T2D patients with acute coronary syndromes.
Author Disclosures: A. Samidurai: None. R.A. Ockaili: None. S.M. Filippone: None. R.C. Kukreja: None. A. Das: None.
- © 2016 by American Heart Association, Inc.