Abstract 251: Comparison of Ischemia-Reperfusion Injury in Langendorff-Prepared Hearts From Zucker Diabetic Fatty and Lean Rats

Abstract

Introduction: The Zucker Diabetic Fatty (ZDF) rat is a relevant model for assessing ischemia-reperfusion (IR) injury, due to it having comorbidities associated with a higher risk for cardiac arrest and poorer outcomes following cardiopulmonary resuscitation in humans. Hypothesis: Based on previous studies in the literature, we hypothesize that ZDF rats would have similar outcomes to lean rats subjected to IR when accounting for perfusion buffer osmolarity. Methods: ZDF (n=4) and lean control (n=6) rats were anesthetized with pentobarbital, intubated, and mechanically ventilated and monitored for 3-hours, with blood glucose (BG) readings taken before and after ventilation. They were then decapitated and a thoracotomy performed to isolate the Langendorff-prepared hearts. Krebs buffer with the osmolarity adjusted to each rat’s BG level using glucose was used to perfuse the hearts. Following a 20-minute stabilization period, the hearts were subjected to a 30-minute period of global no-flow ischemia followed by 120-minutes of reperfusion. Spontaneous heart rate, isovolumetric left ventricular pressure (LVP), and mitochondrial redox state were measured continuously. Data are mean ± SD. Statistics: two-tailed t-test, p<0.05 Results: There was no significant difference in average body weight between the two groups; however, ZDF rats showed significantly higher BG levels (504±52 vs 174±14 mg/dl) than their lean littermates. ZDF rats had a greater percent change from baseline systolic LVP upon reperfusion than lean rats (133±33.3 vs 84.9±16.5 %), with the lean rats never returning to baseline. Diastolic contracture occurred more in lean rats during ischemia, but trended towards a lower contracture during reperfusion. No significant difference was seen in developed LVP, rate pressure products, or mitochondrial redox states, although lean rats trended towards better diastolic contractility and relaxation. Conclusion: Lean rats showed marginally better outcomes in heart function than their ZDF littermates. Future studies will focus on potential mechanisms of Type 2 diabetes that may exacerbate IR injuries.