COMPARISON OF POLARIZED AND DEPOLARIZED ARREST IN THE ISOLATED RAT-HEART FOR LONG-TERM PRESERVATION

Background Hypothermic hyperkalemic cardioplegic solutions are current ly used for donor heart preservation. Hyperkalemia-induced depolarizat ion of the resting membrane potential (E-m) may predispose the heart t o Na+ and Ca2+ loading via voltage-dependent ''window currents,'' ther eby exacerbating injury and limiting the safe storage duration. Altern atively, maintaining the resting E-m with a polarizing solution may re duce ionic movements and improve postischemic recovery; we investigate d 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 preser vation and (2) whether TTX induces and maintains polarized arrest. Met hods and Results The isolated crystalloid-perfused working rat heart p reparation was used In this study. Preliminary studies determined an o ptimal TTX concentration of 22 mu mol/L and an optimal storage tempera ture of 7.5 degrees C. To compare depolarized and polarized arrest, he arts were arrested with either Krebs-Henseleit (KH) buffer (control), KH buffer containing 16 mmol/L K+, or KH buffer containing 22 mu mol/L TTX and then stored at 7.5 degrees C for 5 hours. Postischemic recove ry of aortic flow was 13+/-4%, 38+/-2%, and 48+/-3% (*P<.05 versus co ntrol and 16 mmol/L K+), respectively. When conventional 3 mol/L KCl-f illed intracellular microelectrodes were used, E-m gradually depolariz ed during control unprotected ischemia to approximate to -55 mV before reperfusion, whereas arrest with 16 mmol/L K+ caused rapid depolariza tion to approximate to -50 mV, where it remained throughout the 5-hour storage period. In contrast, in 22 mu mol/L TTX-arrested hearts, E-m remained more polarized, at approximate to -70 mV, for the entire isch emic period. Conclusions Blockade of cardiac sodium channels by TTX du ring ischemia maintained polarized arrest, which was more protective t han depolarized arrest, possibly because of reduced ionic imbalance.