Patent ID: 7615361

Claim:
A method of determining a level of cardiac toxicity of a chemical compound comprising the steps of: (a) providing freshly isolated cardiomyocytes; (b) providing freshly isolated liver cells; (c) culturing the cardiomyocytes and liver cells in the presence of a plurality of concentrations of said chemical compound; (d) measuring two or more indicators of cell health at four or more concentrations of said chemical compound for the cardiomyocytes, wherein the two or more indicators of cell health are each independently selected from the group consisting of indicators of mitochondrial function, indicators of cell membrane integrity, indicators of cell mortality, and indicators of oxidative stress; (e) measuring two or more indicators of cell health at four or more concentrations of said chemical compound for the liver cells, wherein the two or more indicators of cell health are each independently selected from the group consisting of indicators of mitochondrial function, indicators of cell membrane integrity, indicators of cell mortality, and indicators of oxidative stress; (f) determining a level of toxicity of said chemical compound from the measurements taken in steps (d) and (e) by: (1) performing a concentration response analysis for each indicator of cell health from the measurements taken in step (d) for the cardiomyocytes; (2) performing a concentration response analysis for each indicator of cell health from the measurements taken in step (e) for the liver cells; (3) identifying, from the concentration response analyses of (1), the highest concentration of said chemical compound at which no measurable toxic effect was observed for each measured indicator of cell health for the cardiomyoctes; (4) identifying, from the concentration response analyses of (2), the highest concentration of said chemical compound at which no measurable toxic effect was observed for each measured indicator of cell health for the liver cells; (5) selecting, as the toxic concentration (C tox ), a concentration less than or equal to the highest concentration of said chemical compound at which no measurable toxic effect was observed for all measured indicators of cell health in (3) for the cardiomyocytes, as a level of toxicity for the chemical compound in cardiac cells; (6) selecting, as the toxic concentration (C tox ), a concentration less than or equal to the highest concentration of said chemical compound at which no measurable toxic effect was observed for all measured indicators of cell health in (4) for the liver cells, as a level of toxicity for the chemical compound in liver cells; and (g) determining that the chemical compound exhibits cardiac specific toxicity if the C tox calculated in (f)(5) is lower than the C tox calculated in (f)(6).