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(Circulation. 1997;96:3148-3156.)
© 1997 American Heart Association, Inc.

Articles

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

A. K. Snabaitis, BSc; M. J. Shattock, PhD; ; D. J. Chambers, PhD

From Cardiac Surgical Research and Cardiovascular Research (M.J.S.), The Rayne Institute, St Thomas' Hospital, London, UK.

Correspondence to Dr D.J. Chambers, Cardiac Surgical Research, The Rayne Institute, St Thomas' Hospital, London SE1 7EH, UK. E-mail d.chambers{at}umds.ac.uk

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 Ca²⁺ 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.

Key Words: cardioplegia • electrophysiology • depolarizing

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