Chemolysis of cystine calculi.

Historically, cystine stone chemolysis has been approached with 2 different categories of compounds--alkalizing agents (sodium bicarbonate and tromethamine) and, more recently, protonated thiols and disulfide compounds (alpha-mercaptopropionylglycine, N-acetylcysteine and penicillamine). To establish the relative efficacy of these agents an in vitro model was devised that simulates the clinical setting. The optimal molar concentrations for sodium bicarbonate, N-acetylcysteine and tromethamine were determined initially and then compared at these strengths. Lastly, a variety of solution combinations were made to determine if a synergistic effect could be demonstrated. Results of this study demonstrate that the combination of acetylcysteine, a protonated thiol, with the strong alkalizing agent sodium hydroxide yields the most effective solution for chemolysis of cystine stones. The mechanism of action is believed to occur by a synergistic combination of the pH dependent increase in cystine solubility, with a simultaneously occurring thiol disulfide interchange.

Experimental observations on dissolution of uric acid calculi.

An in vitro model was devised to evaluate the efficacy of the different irrigating solutions utilized for local dissolution of uric acid stones. Tris (hydroxymethyl) aminomethane proved to be several times faster than sodium bicarbonate in dissolving uric acid calculi. The maximal dissolution rate was obtained when the highest pH (10.5) of Tris buffer was used in concentrations at or above 0.2 M. This makes the commercially available THAM-E an optimal choice. Stones averaging 1 cm. in diameter were dissolved in less than 48 hours when this compound was used. Sodium bicarbonate should only be used in solutions with concentrations lower than 0.2 M and pH below 9, if some dissolution is to be attempted. Concentrations and pH's above these levels will coat the stones with hard shells of sodium urate, making it impossible to dissolve them. The in vitro findings were confirmed in vivo in a limited study in pigs with human uric acid calculi surgically placed in their kidneys. Our results indicate how to make the best use of the solutions clinically available in order to obtain total dissolution of uric acid stones in short periods of time. We recommend the use of a 0.3 molar concentration of this buffer (THAM-E) at flow rates of about 50 cc per hour.