Abstract 163: Ex Vivo Assessment of Normothermic Myocardial Ischemia/Reperfusion Injury in Winter-Active Arctic Ground Squirrels
Introduction: Hibernating mammals display a striking degree of cardioprotection under extreme physiological conditions. We have shown a manifold reduction in myocardial ischemia/reperfusion (IR) injury in hibernating Arctic Ground Squirrels (AGS) undergoing deep hypothermic circulatory arrest compared to Brown Norway rats (BN). To further delineate the mechanistic basis of endogenous cardioprotection in hibernators, we used an isolated heart model to compare responses of winter active AGS and BN to normothermic IR.
Methods: Langendorff-prepared AGS (n = 4) and BN hearts (n = 8) were perfused (80 mmHg perfusion pressure, 37°C) with Krebs solution (7.5 mM glucose). After 20 min stabilization and 5 min cardioplegic arrest, hearts underwent 45 min global normothermic ischemia and 60 min reperfusion. Left ventricular pressure (LVP) was measured isovolumetrically via a saline-filled latex balloon. Infarct size was determined using TTC staining and cumulative planimetry.
Results: During late ischemia and throughout reperfusion, AGS hearts displayed significantly increased diastolic and systolic LVPs, decreased heart rate, but no difference in developed (systolic-diastolic) LVP, dLVP/dt, coronary flow, or infarct size compared to BN (table).
Conclusion: These first-ever comparative isolated heart experiments in winter active AGS showed remarkable functional differences to the rat strain least susceptible to myocardial IR (BN). The lack of cardioprotection in our model in contrast to deep hypothermic in vivo conditions may be due to differences in hibernation state (torpid versus active AGS), metabolic fuel availability (fatty acid-free perfusate), response to temperature changes, and/or systemic IR injury-aggravating factors between the two species. Moreover, the significant diastolic contracture in AGS suggests fundamental differences in intracellular calcium handling and/or mitochondrial bioenergetics during normothermic IR.
- © 2012 by American Heart Association, Inc.