Hexane and carbon disulfide.

IN AN EARLIER STUDY (Barr et al., 1981) we explored the pathogenesis of soft-tissue necrosis induced in guinea-pigs by the concrolled extravascular administration of cytotoxic drugs. This system provides a model of the phenomenon which may complicate the inadvertent perivenous injection of cancer chemotherapeutic agents in clinical practice. The current investigation was undertaken in order to determine whether the appearance of such lesions could be prevented by secondary prophylaxis. To this end a variety of materials was instilled into the target tissues following the injection of the injurious drugs. Hartley guinea-pigs (Camm Labs, Wayne, New Jersey) were housed and prepared for study as described previously (Barr et al., 1981); three animals were used for each study point. Vincristine was administered intradermally (i.d.) in doses of 2-5 or 5 0 jtg in 03 ml. Adriamycin was injected s.c. at various concentrations in volumes of 1 ml. Agents used for secondary prophylaxis were isotonic phosphatebuffered saline (PBS, pH 7.4), hydrocortisone (at several concentrations), indomethacin (2.8 x 1O-7M) and sodium bicarbonate (8.4%). Indomethacin was prepared for injection by dissolving the contents of one capsule (25 mg) in 5 ml of aqueous dimethyl sulphoxide at 37°C over several hours, and diluting this solution further with water. These agents were administered i.d. in volumes of 1 ml and s.c. in volumes of 5 ml at the sites of prior injection of cytotoxic drugs. Such intervention was used either immediately or 24 h after drug injection. Positive controls were animals receiving vincristine or Adriamycin alone. Negative controls were obtained by injecting animals with the intervention agents alone. Secondary prophylaxis was attempted only by the same route as the original cytotoxic injection. The animals were examined daily for evidence of local injury at the sites of injection. Such reactions were graded in severity according to a simple scale, shown in Table I (Barr et al., 1981). The results are summarized in Tables I and II.