Effect of external pH on heat sensitization by local anesthetics

The sensitization of asynchronous Chinese hamster ovary (CHO) cells to 43 degrees C by procaine, lidocaine, and tetracaine was examined, with the pH of the medium carefully controlled at approximately pH7 and 8. Thermal enhancement factors for 43 degrees C were calculated for the surviving fraction of 0.01. The thermal enhancement factors of the local anesthetics were increased at approximately pH8 by factors of 2-12, depending on the local anesthetic and its concentration. The concentration of the uncharged free base form of the local anesthetic in the culture medium correlated positively with the thermal enhancement factors of each local anesthetic and in a near linear fashion with the thermal enhancement factors for procaine. However, the concentration of the cationic form of the local anesthetics in the growth medium did not correlate with heat sensitization. We conclude that the ability of local anesthetics to sensitize cells to heat killing is dramatically influenced by the extracellular pH, with increased sensitization at the more basic pH's. Secondly, it is the extracellular concentration of the free base form of the local anesthetics that correlates with heat sensitization.