Abstract 12630: Resistance Against Normothermic Myocardial Ischemia/Reperfusion Injury in Summer-Active Arctic Ground Squirrels Is Associated With Preserved Mitochondrial Function
Introduction: Hibernating mammals such as Arctic Ground Squirrels (AGS) exhibit a significant resistance to myocardial ischemia/reperfusion (IR) injury.1 We hypothesized that this species-specific cardioprotection relies on fatty acid utilization and is associated with better preserved mitochondrial function.
Methods: Langendorff-prepared hearts from Brown Norway rats (BN, n=15) and summer-active AGS (n=11) were perfused (80 mmHg perfusion pressure, 37°C) with Krebs solution containing 7.5 mM glucose2,3 +/- 1% intralipid.4 Left ventricular pressure was measured isovolumetrically. Following cardioplegic arrest, 45 min global ischemia and 60 min reperfusion, mitochondria were isolated and O2 consumption measured for complex I and II substrates.
Results: Multiple regression analysis showed species (AGS), intralipid, and female gender as predictors of better contractility and rate-pressure-product following IR. In addition, AGS mitochondria had higher respiratory control indices for complex I and II substrates.
Discussion: Several novel findings result from these first-ever isolated heart experiments in summer-active AGS. Even under non-hibernating, normothermic conditions, AGS hearts are better protected against IR injury than the best protected rat strain (BN). This suggests that reduced metabolism during hibernation is not the only factor for cellular protection in hibernating mammals. Instead, season-independent endogenous mechanisms leading to improved mitochondrial function may play an important role. The largely improved outcome in intralipid-perfused AGS vs BN suggests a species-dependency for intralipid-induced cardioprotection5 and challenges the paradigm that increased glucose utilization and inhibition of fatty acid metabolism is beneficial during myocardial IR. Thus, the role of fatty acid metabolism and intralipid administration for cardioprotection warrants further investigation. Supported by Department of Veterans Affairs (CARA-026-10F), FAER, NSF, NIH (R01 HL092071), USAMRMC and institutional funds.
References: 1) Circulation 2012;126:A19524
2) Circulation 2012;126:A163
3) Anaesth Intensivmed 2013;54:S354
4) Anesthesiology 2012;117:836-46
5) Anesthesiology 2013;118:1237-8
- © 2013 by American Heart Association, Inc.