Investigation of acute cardiovascular and respiratory toxicity of HLö 7 dimethanesulfonate and HI 6 dichloride in anaesthetized guinea-pigs.

The bis-pyridinium dioxime HLö 7 is considered to possess promising therapeutic properties in the treatment of organophosphate poisoning. Acute circulatory and respiratory effects of HLö 7 and HI 6 were therefore compared in anaesthetized guinea-pigs. Female Pirbright white guinea-pigs were anaesthetized with urethane and the carotid artery, jugular vein and trachea were cannulated. Saline or atropine, 10 mg/kg, or HLö 7 or HI 6 (30 or 100 mumol/kg, each) or atropine plus oxime were injected intravenously after base line measurements. Respiratory and circulatory parameters were recorded for 60 min., then blood was drawn for AChE measurement. Injection of HLö 7 or HI 6 alone resulted in a temporary, dose-dependent hypotension, an almost unchanged heart rate and a slight respiratory stimulation. A more severe hypotension appeared after the administration of atropine plus HLö 7 or HI 6. In these groups heart rate and respiration were markedly stimulated. Measurement of AChE activity in blood samples revealed no impairment by HLö 7 or HI 6 with or without atropine. These results suggest that HLö 7 has only transient effects on the cardiorespiratory system after intravenous administration and its safety regarding acute circulatory and respiratory toxicity is comparable to HI 6.