Tomoaki Tokuno (1), Minoru Watanabe (2) and Yuji Imaizumi (1,*)
(1) Department of Pharmacology & Therapeutics and (2) Department
of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Nagoya City
University, Nagoya 467 - 8603, Japan
(*) To whom correspondence should be addressed.
Abstract: 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.
Keywords: pH, Lactate, Ischemia, Reperfusion, Cardiac myocyte