Comparison of polarized and depolarized arrest in the isolated rat heart for long-term preservation.
BACKGROUND
Hypothermic hyperkalemic cardioplegic solutions are currently used for donor heart preservation. Hyperkalemia-induced depolarization of the resting membrane potential (Em) 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 Em 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.


RESULTS
The isolated crystalloid-perfused working rat heart preparation was used in this study. Preliminary studies determined an optimal TTX concentration of 22 micromol/L and an optimal storage temperature of 7.5 degrees 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 micromol/L TTX and then stored at 7.5 degrees 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, Em gradually depolarized during control unprotected ischemia to approximately -55 mV before reperfusion, whereas arrest with 16 mmol/L K+ caused rapid depolarization to approximately -50 mV, where it remained throughout the 5-hour storage period. In contrast, in 22 micromol/L TTX-arrested hearts, Em remained more polarized, at approximately -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.
Snabaitis
A K
AK
Cardiac Surgical Research and Cardiovascular Research, The Rayne Institute, St Thomas' Hospital, London, UK.
Shattock
M J
MJ
Chambers
D J
DJ
D000818:Animals; D006324:Heart Arrest, Induced; D008297:Male; D009206:Myocardium / Q000378:metabolism; D009926:Organ Preservation; D011188:Potassium / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013696:Temperature; D013779:Tetrodotoxin / Q000494:pharmacology
D015221:Potassium Channels; D013779:Tetrodotoxin; D011188:Potassium