Long-term myocardial preservation: effects of hyperkalemia, sodium channel, and Na/K/2Cl cotransport inhibition on extracellular potassium accumulation during hypothermic storage.
OBJECTIVE
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 micromol/L) arrest and hypothermic (7.5 degrees C) storage (5 hours), (2) to determine dose-dependent (0.1, 1.0, 10 and 100 micromol/L) effects of the Na +/K+/2Cl- cotransport inhibitor, furosemide, on extracellular K+ accumulation during polarized arrest and 7.5 degrees 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 micromol/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.
Snabaitis
A K
AK
Cardiac Surgical Research and Cardiovascular Research, The Rayne Institute, St Thomas' Hospital, London, United Kingdom.
Shattock
M J
MJ
Chambers
D J
DJ
D000818:Animals; D018118:Chloride Channels / Q000187:drug effects*; D004195:Disease Models, Animal; D004232:Diuretics / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D005110:Extracellular Space / Q000187:drug effects*; D005665:Furosemide / Q000494:pharmacology*; D005947:Glucose / Q000737:chemistry / Q000494:pharmacology; D006324:Heart Arrest, Induced / Q000009:adverse effects / Q000379:methods*; D016027:Heart Transplantation; D006947:Hyperkalemia / Q000150:complications* / Q000378:metabolism; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000209:etiology / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D009926:Organ Preservation / Q000009:adverse effects / Q000379:methods*; D051381:Rats; D017208:Rats, Wistar; D015222:Sodium Channels / Q000187:drug effects*; D000254:Sodium-Potassium-Exchanging ATPase / Q000187:drug effects*; D013779:Tetrodotoxin / Q000494:pharmacology*; D013997:Time Factors; D014325:Tromethamine / Q000737:chemistry / Q000494:pharmacology
D018118:Chloride Channels; D004232:Diuretics; C074097:Krebs-Henseleit solution; D015222:Sodium Channels; D014325:Tromethamine; D013779:Tetrodotoxin; D005665:Furosemide; D000254:Sodium-Potassium-Exchanging ATPase; D005947:Glucose