Inhibition of sodium influx and improved preservation of rat hearts during hypothermic ischemia by furosemide and bumetanide: a 23Na- and 31P-NMR study.
The importance of the Na+/K+/Cl- co-transport system of the rat myocardial sarcolemma was studied under hypothermic ischemia by investigating the effect of the co-transport blockers furosemide and bumetanide on the sodium influx into the myocardium. The intracellular Na+ accumulation during hypothermic ischemia was followed by 23Na-NMR. For this purpose the shift reagent [Dy(TTHA)3-] (SR) was added to the Krebs-Henseleit (KH) perfusion solution. The same solution was also present during the hypothermic preservation. A significant reduction in the intracellular Na+ accumulation after 12 h was found when 100 microM furosemide was present during the perfusion and preservation periods. The intracellular Na+ levels returned to the pre-ischemic values after 1 h of reperfusion with KH in both the treated and control groups. Dose-response studies have indicated that 1-100 microM furosemide or 0.1 microM bumetanide added to the KH-SR solution reduced the Na+ influx significantly over 4 h of hypothermic ischemia. No statistically significant effect was found with furosemide concentration of 0.1 microM or with bumetanide concentrations higher or lower than 0.1 microM. 31P-NMR measurements showed no effect of the 100 microM furosemide on the intracellular ATP, the sum of inorganic phosphate and phosphomonoester, or pH levels over 4 h or after 12 h of hypothermic ischemia. Hearts treated with KH containing 100 microM furosemide showed, significantly higher functional recovery after 12 h of hypothermic ischemia than hearts treated only with KH. This study strongly indicates the existence of the Na+/K+/Cl- co-transport system in the intact rat heart sarcolemma, and its major role in sodium influx during hypothermic ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)
Rubin
Y
Y
Sackler School of Medicine, Department of Physiology and Pharmacology, Tel-Aviv University, Israel.
Navon
G
G
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002034:Bumetanide / Q000494:pharmacology*; D002712:Chlorides / Q000493:pharmacokinetics; D015925:Cryopreservation; D004734:Energy Metabolism / Q000187:drug effects; D005665:Furosemide / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D009926:Organ Preservation / Q000379:methods*; D010761:Phosphorus Radioisotopes / Q000493:pharmacokinetics; D011188:Potassium / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012508:Sarcolemma / Q000378:metabolism; D012964:Sodium / Q000494:pharmacology*; D012979:Sodium Radioisotopes / Q000493:pharmacokinetics
D002712:Chlorides; D010761:Phosphorus Radioisotopes; D012979:Sodium Radioisotopes; D002034:Bumetanide; D005665:Furosemide; D012964:Sodium; D011188:Potassium