Evaluation of Short-Term Bioassays to Predict Functional Impairment. Selected Short-Term Cardiovascular Toxicity Tests

摘要

The MITRE Corporation has been requested by the U.S. Army Medical Bioengineering Research and Development Laboratory to identify and evaluate short-term bioassays which have demonstrated ability to assess and predict impairment of the cardiovascular system resulting from exposure to chemicals. This document reviews the literature on test procedures for determining toxic effects on the heart and other components of the cardiovascular system. The procedures are ranked in descending order of utility and application to a screening program. The recommended tests include both in vivo and in vitro techniques. The in vivo functional techniques recommended are the monitoring of left ventricular pressure, arterial pressure, aortic flow, cardiac output and electrocardiographic activity. The morphological techniques recommended include gross inspection, light microscopy and limited electron microscopy. The biochemical analyses recommended include serum lactic dehydrogenase (LDH), creatine phosphokinase (CPK) and tissue electrolytes (e.g., magnesium, calcium, sodium and potassium). The in vitro techniques recommended are cultured heart cells and perfused heart preparations. In both the cell cultures and perfused heart preparations, various biochemical (e.g., LDH, CPK) and functional (e.g., beating and electrical activity) parameters may be monitored.