Effect of lidocaine on contracture, intracellular sodium, and pH in ischemic rat hearts.
The relationships among intracellular Na concentration ([Na+]i), intracellular pH, [ATP], and contracture during global ischemia were studied in isolated, perfused rat hearts. Intracellular Na was monitored by 23Na nuclear magnetic resonance (NMR) spectroscopy using thulium 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetra(methylene phosphonate) (TmDOTP5-) as the paramagnetic shift reagent. High-energy phosphates and pH were monitored under the same conditions using 31P-NMR spectroscopy. Lidocaine (130 microM), a class IB fast Na channel blocker known to protect ischemic myocardium, prolonged the time to contracture in both unpaced and paced hearts (240 beats/min). After 10 min of global ischemia in paced hearts, [Na+]i was lower in the lidocaine-treated group compared with untreated hearts. The addition of lidocaine also significantly attenuated the depletion of ATP as well as development of intracellular acidosis. At the time of contracture, however, there was no difference in [Na+]i or pH between the two groups. Interestingly, the effect of lidocaine on Na+i accumulation during ischemia was manifested during the first 5-10 min of ischemia, while its effect on pH occurred after 9 min. This finding suggests that a mechanism other than the Na-H exchanger may play a role in the accumulation of Na+i early in the course of ischemia.
Butwell
N B
NB
Department of Radiology, Mary Nell and Ralph B. Rogers Magnetic Resonance Center, University of Texas Southwestern Medical Center, Dallas.
Ramasamy
R
R
Lazar
I
I
Sherry
A D
AD
Malloy
C R
CR
D000818:Animals; D002304:Cardiac Pacing, Artificial; D003327:Coronary Disease / Q000378:metabolism / Q000503:physiopathology*; D006863:Hydrogen-Ion Concentration; D007425:Intracellular Membranes / Q000378:metabolism; D008012:Lidocaine / Q000494:pharmacology*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism*; D010710:Phosphates / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000378:metabolism*
D010710:Phosphates; D008012:Lidocaine; D012964:Sodium