Long-term myocardial preservation: Effects of hyperkalemia, sodium channel, and Na+/K+/2Cl(-) cotransport inhibition on extracellular potassium accumulation during hypothermic storage

Objectives: We previously demonstrated improved myocardial preservation wit h polarized (tetrodotoxin-induced), compared with depolarized (hyperkalemia -induced), arrest and hypothermic storage. This study was undertaken to det ermine whether polarized arrest reduced ionic imbalance during ischemic sto rage and whether this was influenced by Na+/K+/2Cl(-) cotransport inhibitio n. Methods: We used the isolated crystalloid perfused working rat heart pre paration (1) to measure extracellular Kf accumulation (using a Kt-sensitive intramyocardial electrode) during ischemic (control), depolarized (K+ 16 m mol/L), and polarized (tetrodotoxin, 22 mu mol/L) arrest and hypothermic (7 .5 degrees C) storage (5 hours), (2) to determine dose-dependent (0.1, 1.0, 10 and 100 mu mol/L) effects of the Na+/K+/2Cl(-) cotransport inhibitor, f urosemide, on extracellular K+ accumulation during polarized arrest and 7.5 degrees C storage, and (3) to correlate extracellular K+ accumulation to p ostischemic recovery of cardiac function. Results: Characteristic triphasic profiles of extracellular K+ accumulation were observed in control and dep olarized arrested hearts; a significantly attenuated profile with polarized arrested hearts demonstrated reduced extracellular K+ accumulation, correl ating with higher postischemic function (recovery of aortic flow was 54% +/ - 4% [P = .01] compared with 39% +/- 3% and 32% +/- 3% in depolarized and c ontrol hearts, respectively). Furosemide (0.1, 1.0, 10, and 100 mu mol/L) m odified extracellular K+ accumulation by -18%, -38%, -0.2%, and +9%, respec tively after 30 minutes and by -4%, -27%, +31%, and +42%, respectively, aft er 5 hours of polarized storage. Recovery of aortic flow was 53% +/- 4% (po larized arrest alone), 56% +/- 8%, 70% +/- 2% (P = .04 vs control), 69% +/- 4% (P = .04 vs control), and 65% +/- 3% (P = .04 vs control), respectively . Conclusions: Polarized arrest was associated with a reduced ionic imbalan ce (demonstrated by reduced extracellular K+ accumulation) and improved rec overy of cardiac function. Further attenuation of extracellular K+ accumula tion (by furosemide) resulted in additional recovery.