Metabolic, cardiovascular, and neurologic aspects of acute cyanide poisoning in the rat

Abstract

Acute cyanide (CN) toxicity was investigated in the Sprague-Dawley rat. Conscious, loosely restrained rats received sodium CN solution at varying dose rates through a jugular cannula (low CN, 0.077–0.155 mg/kg/min; high CN, 0.157–0.204 mg/kg/min). Blood glucose concentration was significantly increased 45 min after initial CN treatment in both the low and the high CN groups compared to the saline controls. Blood lactate concentration was significantly increased only in the high CN group after 45 min. Lactate increased directly with CN dose rate in surviving high CN rats. In rats that succumbed during CN infusion, lactate concentration reached nearly 150 mg/dl. Body temperature decreased modestly at low CN dose rates, but increased markedly at high CN dose rates. Heart rate was relatively constant in the low CN group, but decreased rapidly in the high CN group with increasing CN dose rate. In rats surviving CN treatment, no significant alterations in either cerebral cortical water content or neurologic status were detected. This contrasts with another potent poison, carbon monoxide, which produces marked neurologic deficit and cerebral edema in this animal model. The mean lethal CN dose was 4.6 mg/kg (range 4.25–4.90 mg/kg). Expressed on the basis of CN infusion rate, the lethal zone was from 0.16 to 0.21 mg/kg/min, a surprisingly narrow range. Assuming that extrapolations are possible to other species, the data provide strong evidence that greatly elevated blood lactate may be a useful marker for CN poisoning very near or within the lethal zone.