Effect of Therapeutic Intervention on Pathophysiology, Pathology, and Survival in Rats and Swine Following Acute Intravenous Exposure to T-2 Toxin

Abstract

Rats and swine were used to assess the efficacy of a number of drugs for the treatment of acute T-2 toxicosis induced by the intravenous administration of lethal doses of T-2 toxin. In rats, efficacy was assessed by analysis of survival times and rates and the severity of histologic tissue lesions in target organs. In swine, efficacy was assessed by analysis of survival times and rates and changes in physiologic parameters.

The therapeutic efficacy of diltiazem hydrochloride, methylprednisolone sodium succinate (MPSS), dazemgrel, N-acetylcysteine, dimethyl sulfoxide, trichodermin, adenosine triphosphate alone and in combination with magnesium chloride, ascorbic acid, aprotinin, superactivated charcoal (SAC), dexamethasone sodium phosphate (DEX), and prostaglandin E$\sb1$ alone and in combination with DEX was assessed in rats. At the doses used, only MPSS and DEX, given after T-2 toxin iv at 1 mg/kg, and SAC, given before T-2 toxin iv at 0.8 mg/kg, significantly improved survival times and rates. Trichodermin given either 2 hr prior to or 1 hr after T-2 toxin iv at 1 mg/kg significantly improved survival times and rates. Trichodermin given either 2 hr prior to or 1 hr after T-2 toxin iv at 1 mg/kg significantly decreased survival times. The iv administration of MPSS lessened the severity of T-2 induced histologic lesions in the stomach and the spleen, whereas the oral administration of SAC lessened the severity of T-2 induced histologic lesions in the ileum and closely associated lymphoid tissue (Peyer's patches).

The efficacy of 4 therapeutic protocols was assessed in swine given T-2 toxin iv at 3.6 mg/kg (3X LD$\sb{50}$). One group was given metoclopramide, DEX, normal saline, sodium bicarbonate, and SAC in combination with magnesium sulfate (all therapy). The other 3 treatment groups were given all therapy less 1 of the following: normal saline, sodium bicarbonate, or SAC + magnesium sulfate. There were significantly improved survival rates and times in the treatment group given SAC + magnesium sulfate compared to the groups given all therapy less SAC + magnesium sulfate. The administration of normal saline did not maintain aortic mean blood pressure, whereas the administration of sodium bicarbonate ameliorated declines in arterial blood pH. Significant elevations in serum magnesium concentrations were noted in the treatment groups in which magnesium sulfate was included.