Effects of lactate on intracellular pH and hypercontracture during simulated ischemia and reperfusion in cardiac ventricular myocytes of the guinea pig.
Effects of lactate on changes in intracellular pH (pHi) and contractility during simulated ischemia and reperfusion were examined in single myocytes of the guinea pig cardiac ventricle. The conditions of simulated ischemia were produced by the exchange of perfusion medium from the standard one oxygenated with 95% O2-5% CO2 gas (pH 7.4) to one containing no glucose, 8 mM K+, and 0-30 mM sodium-D,L-lactate and was gassed with 90% argon - 10% CO2 (pH 6.6). The pHi was decreased by the simulated ischemia from approx. 7.3 to approx. 6.9 regardless of lactate concentration, while the rate of pHi decrease was increased by lactate in a concentration-dependent manner. The contraction induced by electrical stimulation disappeared faster in the presence of lactate. The incidence of irreversible hypercontracture of myocytes was significantly reduced by 20-30 mM lactate. The overshoot of pHi to approx. 7.7 and excess contractions were induced by withdrawal of lactate during the reperfusion, but not observed when lactate was continuously present. The recovery of normal contractility during reperfusion was facilitated by lactate. It can be concluded that lactate added to or removed from the perfusion medium increases the rate of pHi change under the simulated ischemia and reperfusion, respectively, and that the continuous presence of lactate reduces cell injury under these conditions.
Tokuno
T
T
Department of Pharmacology & Therapeutics, Faculty of Pharmaceutical Sciences, Nagoya City University, Nagoya, Japan.
Watanabe
M
M
Imaizumi
Y
Y
D000818:Animals; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D006168:Guinea Pigs; D006352:Heart Ventricles / Q000187:drug effects*; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D019344:Lactic Acid / Q000494:pharmacology*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D017202:Myocardial Ischemia / Q000473:pathology*; D015425:Myocardial Reperfusion / Q000009:adverse effects*; D013997:Time Factors
D019344:Lactic Acid