Offspring of Sprague-Dawley dams injected SC with 40 mg/kg/3 cc cocaine HCl daily from gestational days 8-20, pair-fed dams injected with the vehicle alone and nontreated control dams were examined behaviorally during the early postnatal period. No significant differences were observed among the treatment conditions in maternal weight gain during pregnancy, duration of pregnancy, or number of live male and female pups/litter. Offspring body weights at birth and weaning, physical maturation and reflex development were not significantly affected by prenatal cocaine exposure. In contrast, neonates exposed prenatally to cocaine were observed to exhibit significant deficits in learning of an odor/milk association that nontreated offspring learned and retained for a 24 hr period. On postnatal day 12, cocaine offspring exhibited an increase in locomotor activity and attenuated wall climbing precipitated by footshock, in the absence of any alteration in sensitivity to footshock. Given that wall climbing has been previously shown to be strongly related to levels of catecholamine activity at this age, these data suggest the possibility that there may be some attenuation in catecholaminergic function in pups exposed gestationally to cocaine. The results of this study provide evidence that prenatal cocaine exposure may have an impact upon behavioral and cognitive function even during the early postnatal period. More work is needed to fully characterize the range of alterations observed and the neural mechanisms underlying these early exposure effects.

Animals↗

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Arterial oxygen tensions.

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Anesthesia↗

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A simplified technique for cannulation of the jugular bulb.

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Blood Specimen Collection↗

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Myoglobinuric acute renal failure in the rat: a role for acidosis?

Myoglobin induces renal injury by mechanisms that remain incompletely defined. Acidosis has been suggested as an important factor in myoglobinuric renal failure, and urine alkalization is routinely recommended for its prevention. We tested this hypothesis by exploring the effects of acid-base balance upon myoglobin nephrotoxicity in vivo and in vitro. In isolated rat kidneys at normal pH, myoglobin at concentrations of 25-250 mg/dl minimally affected renal perfusion flow, glomerular filtration rate (GFR) and tubular sodium reabsorption (TRNa). By contrast, at pH 7.1 myoglobin induced vasoconstriction, reduced GFR and TRNa and increased hypoxic injury to medullary thick ascending limbs. These changes were largely reproduced by perfusing kidneys with hematin, suggesting its release from myoglobin in acidosis. Chronic alkalosis or acidosis was induced in rats by supplementing drinking water with 0.28 M NaHCO3 or NH4Cl, respectively. Acute renal failure, produced in control animals by myoglobin infusion (38 mg/100 g body weight), was comparably prevented by both chronic alkalosis and acidosis. Acute intravenous or oral acid load provided similar protection. Thus, although acidosis exacerbates myoglobin toxicity in isolated perfused kidneys, acute or chronic exogenous acid load prevents renal damage in vivo. This may underscore the protective properties of solute load, a consequence of preconditioning, and suggests that, in the crush syndrome, endogenous acidosis rather than being an independent risk factor is a marker of tissue hypoperfusion and organism susceptibility to myoglobin renal toxicity.

Acid-Base Equilibrium↗