The cardiovascular effects of two monocarboxylic inophores, grisorixin and alborixin, in anesthetized guinea-pigs.

ABSTRACT

Grisorixin and alborixin are two monocarboxylic ionophorous antibiotics of nigericin group which form neutral complexes with monovalent cations, preferentially K+, so they are able to modify biological membrane permeability to these cations. The toxicity of these two compounds in aqueous ethanol was studied in guinea-pigs by i.v. perfusion of the solution at the rate of 0.4 mg/kg/min. Alborixin appeared to be two times more toxic than grisorixin and they both produced a marked increase in arterial blood pressure within 5 and 10 min after the beginning of the perfusion, together with ECG modifications such as conduction and repolarization disorders. Similar effects were observed in animals treated by a single injection of grisorixin (2 mg/kg) or alborixin (1 mg/kg). Under these conditions both antibiotics were found to produce a tremendous increase in kaliemia (+ 200%) and a concomitant hyponatremia. They did not modify intramyocardial ATP and ADP levels but they might affect creatine phosphate concentration as shown by an increase in inorganic P levels. It is suggested that the cardiovascular effects observed are due to the alterations in intra- and extracellular ionic activities by grisorixin and alborixin.