Comparison of Polarized and Depolarized Arrest in the Isolated Rat Heart for Long-term Preservation

Abstract

Background Hypothermic hyperkalemic cardioplegic solutions are currently used for donor heart preservation. Hyperkalemia-induced depolarization of the resting membrane potential (E m ) may predispose the heart to Na + and Ca 2+ loading via voltage-dependent “window currents,” thereby exacerbating injury and limiting the safe storage duration. Alternatively, maintaining the resting E m with a polarizing solution may reduce ionic movements and improve postischemic recovery; we investigated this concept with the reversible sodium channel blocker tetrodotoxin (TTX) to determine (1) whether polarized arrest was more efficacious than depolarized arrest during hypothermic long-term myocardial preservation and (2) whether TTX induces and maintains polarized arrest. Methods and Results The isolated crystalloid-perfused working rat heart preparation was used in this study. Preliminary studies determined an optimal TTX concentration of 22 μmol/L and an optimal storage temperature of 7.5°C. To compare depolarized and polarized arrest, hearts were arrested with either Krebs-Henseleit (KH) buffer (control), KH buffer containing 16 mmol/L K + , or KH buffer containing 22 μmol/L TTX and then stored at 7.5°C for 5 hours. Postischemic recovery of aortic flow was 13±4%, 38±2%, and 48±3%* (* P <.05 versus control and 16 mmol/L K + ), respectively. When conventional 3 mol/L KCl-filled intracellular microelectrodes were used, E m gradually depolarized during control unprotected ischemia to ≈−55 mV before reperfusion, whereas arrest with 16 mmol/L K + caused rapid depolarization to ≈−50 mV, where it remained throughout the 5-hour storage period. In contrast, in 22 μmol/L TTX-arrested hearts, E m remained more polarized, at ≈−70 mV, for the entire ischemic period. Conclusions Blockade of cardiac sodium channels by TTX during ischemia maintained polarized arrest, which was more protective than depolarized arrest, possibly because of reduced ionic imbalance.