RESUMO
Maternal cocaine abuse may increase the incidence of perinatal asphyxia. In nonexposed asphyxiated neonates, decreased cerebrospinal fluid (CSF) cAMP concentrations are associated with poor neurological outcome. On the other hand, cocaine increases central nervous system (CNS) cAMP. Therefore, we hypothesized that in utero cocaine exposure may increase brain cAMP and thereby preserve cerebrovascular responses to cAMP-dependent stimuli following asphyxia. Pregnant pigs received either cocaine (1 mg/kg, i.v.) twice weekly during the last trimester or normal saline vehicle (sham-control) and were allowed to deliver vaginally at term. Cranial windows were implanted in the newborn pigs within the first week of life and used to collect CSF for cAMP determinations and to assess changes in pial arteriolar diameters (PAD). In the first part of the study, pial arteriolar responses to different vasodilator and vasoconstrictor stimuli were evaluated in piglets prior to asphyxia (n = 20). In newborn pigs exposed to cocaine, cerebrovascular responses to hypercapnia and norepinephrine were significantly exaggerated compared to controls. Then, piglets were randomly selected for the second part of the study that involved prolonged asphyxia (n = 12). In cocaine-exposed but not sham-control piglets, CSF cAMP increased markedly during asphyxia. In the sham piglets, but not the cocaine-exposed piglets, CSF cAMP fell progressively below the baseline during recovery. Cerebrovascular reactivity to cAMP-dependent stimuli (hypercapnia and isoproterenol) was preserved during recovery from asphyxia in the cocaine-exposed piglets but significantly attenuated in the sham controls. We conclude that piglets with chronic prenatal exposure to cocaine show exaggerated cerebrovascular responses to vasogenic stimuli and preserved cAMP-dependent cerebral vasoreactivity following asphyxia.
Assuntos
Circulação Cerebrovascular/efeitos dos fármacos , Cocaína/toxicidade , Efeitos Tardios da Exposição Pré-Natal , Animais , Animais Recém-Nascidos , Arteríolas/efeitos dos fármacos , Arteríolas/fisiopatologia , Pressão Sanguínea/efeitos dos fármacos , Dióxido de Carbono/sangue , AMP Cíclico/líquido cefalorraquidiano , AMP Cíclico/metabolismo , Feminino , Concentração de Íons de Hidrogênio , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/fisiopatologia , Oxigênio/sangue , Pressão Parcial , Gravidez , SuínosRESUMO
Maternal cocaine abuse is associated with fetal and neonatal neurological abnormalities. Prolonged exposure to cocaine can induce blood flow disorders, growth restriction, and hypoxia in the newborn. We investigated the impact of chronic fetal cocaine exposure on cerebral microvascular reactivity and autonomic function in the piglets. Pregnant pigs received cocaine (1 mg/kg i.v.; twice weekly) or saline throughout the last trimester. Prenatal exposure to cocaine did not have any significant effect on the birth weight of the piglets as compared to the control. Following delivery, effects of recurrent prenatal cocaine exposure on cerebral microvascular functions were examined in piglets (3-6 days old). Pial arteriolar responses to applications of 5-hydroxytryptamine (5-HT), endothelin-1 (ET-1), and clonidine were examined using closed cranial windows. Functional effects of prenatal cocaine exposure on changes in mean arterial pressure (MAP) and pial arteriolar diameter induced by intracisternal injection (i.c.) of clonidine (1 microg/kg) were also determined. Topical applications of 5-HT, ET-1, and clonidine dose-dependently decreased pial arteriolar diameter in the control and these constrictions were significantly enhanced in the in utero cocaine-exposed piglets. Prenatal cocaine exposure did not have any significant effects on the resting MAP and heart rate as there were no differences between the groups. IC clonidine caused sustained decrease in MAP in both groups but the decrease was more pronounced in the cocaine than the control group. IC clonidine causes cerebral microvascular dilation coincident with the development of hypotension. Such dilation was severely attenuated in the cocaine group, even though the hypotension was much more pronounced than in the control. In conclusion, prenatal cocaine exposure resulted in attenuated autoregulatory vasodilation and potentiated responses to vasoconstrictor agents. The mechanisms behind the effects of in utero cocaine exposure on alteration of newborn cerebral functions need further investigation. Such actions may be important in development of cerebral pathologies associated with recurrent prenatal cocaine exposure.
Assuntos
Circulação Cerebrovascular/efeitos dos fármacos , Clonidina/farmacologia , Cocaína/efeitos adversos , Endotelina-1/metabolismo , Pia-Máter/irrigação sanguínea , Efeitos Tardios da Exposição Pré-Natal , Serotonina/metabolismo , Simpatolíticos/farmacologia , Vasoconstritores/efeitos adversos , Animais , Animais Recém-Nascidos , Arteríolas/efeitos dos fármacos , Sistema Nervoso Autônomo/efeitos dos fármacos , Peso ao Nascer/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Relação Dose-Resposta a Droga , Endotelina-1/farmacologia , Feminino , Feto , Frequência Cardíaca/efeitos dos fármacos , Masculino , Gravidez , Serotonina/farmacologia , Suínos , Vasoconstrição/efeitos dos fármacos , Vasodilatação/efeitos dos fármacosRESUMO
Oral activated charcoal (OAC) is a universally accepted treatment of the overdose patient. Although the benefits of OAC have been suggested, there are no conclusive clinical data indicating that OAC affects outcome in overdose patients. This study was a prospective, randomized, controlled trial to determine the effects of OAC treatment in the self-poisoned adult patient. Adult patients presenting to the emergency department (ED) with a history of oral overdose were assigned to treatment with OAC (50 g) or supportive care only on an even-odd day protocol. Patients did not undergo gastric evacuation procedures in the ED. The outcome measures were clinical deterioration, length of stay in the ED or hospital, and complication rate. Over a 24-month period, 1479 patients were entered into the study. There were no significant differences in outcome parameters between the OAC treatment group and controls when comparing the length of intubation time, length of hospital stay, and the complication rates associated with the overdose. There was a higher incidence of vomiting and longer length of ED stay associated with OAC treatment. The results of this study indicated that oral drug overdose patients do not require gastric evacuation or charcoal administration. OAC provided no additional benefit to supportive care alone, was associated with a higher incidence of vomiting and a longer length of ED stay, and did not improve clinical outcome.