Quantitative Morphometric Analysis of Myocardial Injury in Rabbits Following the Administration of Anthracycline Drugs

摘要

Quantitative measurements were carried out on samples from histological sections of the hearts of 45 rabbits exposed to Adriamycin (ADR), four test analogs of ADR and saline injected controls. Volume fraction of normal tissue components and of tissue elements indicating drug induced injury, and surface density of muscle fibers were determined by morphometric methods using the Merz grid. The method was able to distinguish the two most toxic drugs and has the capability to generate a cardiotoxicity spectrum according to several morphometrically determined parameters. Analysis of the results indicates that individual susceptability contributes to the larger standard deviations associated with the means of the more toxic drugs. Among groups of less toxic analogs sampling methods more sensitive to minimal heart damage may be required in order to rank their cardiotoxic effects. Measurements made on the hearts of a limited number of animals to which different doses of ADR were administered indicate that a dose response curve can be generated morphometrically.