Effects of respiratory acidosis and alkalosis on the distribution of cyanide into the rat brain

The aim of this study was to determine whether respiratory acidosis favors the cerebral distribution of cyanide, and conversely, if respiratory alkalo sis limits its distribution. The pharmacokinetics of a nontoxic dose of cya nide were first studied in a group of 7 rats in order to determine the dist ribution phase. The pharmacokinetics were found to best fit a 3-compartment model with very rapid distribution (whole blood T(1/2)alpha = 21.6 +/- 3.3 s), Then the effects of the modulation of arterial pH on the distribution of a nontoxic dose of intravenously administered cyanide into the brains of rats were studied by means of the determination of the permeability-area p roduct (PA), The modulation of arterial blood pH was performed by variation of arterial carbon dioxide tension (PaCO2) in 3 groups of 8 anesthetized m echanically ventilated rats. The mean arterial pH measured 20 min after the start of mechanical ventilation in the acidotic, physiologic, and alkaloti c groups were 7.07 +/- 0.03, 7.41 +/- 0.01, and 7.58 +/- 0.01, respectively . The mean PAs in the acidotic, physiologic, and alkalotic groups, determin ed 30 s after the intravenous administration of cyanide, were 0.015 +/- 0.0 02, 0.011 +/- 0.001, and 0.008 +/- 0.001 s(-1), respectively tone-way ANOVA ; p < 0.0087), At alkalotic pH the mean permeability-area product was 43% o f that measured at acidotic pH, This effect of pH on the rapidity of cyanid e distribution does not appear to be limited to specific areas of the brain . We conclude that modulation of arterial pH by altering PaCO2 may induce s ignificant effects on the brain uptake of cyanide.