Long-term myocardial preservation: effects of hyperkalemia, sodium channel, and NA +/K +/2CL - cotransport inhibition on extracellular potassium accumulation during hypothermic storage

Abstract

Objectives: We previously demonstrated improved myocardial preservation with polarized (tetrodotoxin-induced), compared with depolarized (hyperkalemia-induced), arrest and hypothermic storage. This study was undertaken to determine whether polarized arrest reduced ionic imbalance during ischemic storage and whether this was influenced by Na +/K +/2Cl - cotransport inhibition. Methods: We used the isolated crystalloid perfused working rat heart preparation (1) to measure extracellular K + accumulation (using a K +-sensitive intramyocardial electrode) during ischemic (control), depolarized (K + 16 mmol/L), and polarized (tetrodotoxin, 22 μmol/L) arrest and hypothermic (7.5°C) storage (5 hours), (2) to determine dose-dependent (0.1, 1.0, 10 and 100 μmol/L) effects of the Na +/K +/2Cl - cotransport inhibitor, furosemide, on extracellular K + accumulation during polarized arrest and 7.5°C storage, and (3) to correlate extracellular K + accumulation to postischemic recovery of cardiac function. Results: Characteristic triphasic profiles of extracellular K + accumulation were observed in control and depolarized arrested hearts; a significantly attenuated profile with polarized arrested hearts demonstrated reduced extracellular K + accumulation, correlating with higher postischemic function (recovery of aortic flow was 54% ±4% [ P = .01] compared with 39% ±3% and 32% ±3% in depolarized and control hearts, respectively). Furosemide (0.1, 1.0, 10, and 100 μmol/L) modified extracellular K + accumulation by –18%, –38%, –0.2%, and +9%, respectively, after 30 minutes and by –4%, –27%, +31%, and +42%, respectively, after 5 hours of polarized storage. Recovery of aortic flow was 53% ±4% (polarized 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 imbalance (demonstrated by reduced extracellular K + accumulation) and improved recovery of cardiac function. Further attenuation of extracellular K + accumulation (by furosemide) resulted in additional recovery. (J Thorac Cardiovasc Surg 1999;118:123-34)