title: Chronic prenatal exposure to cocaine alters cerebrovascular responses in newborn pigs.
abstract: 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.
authors.affiliation: Laboratory for Research in Neonatal Physiology, Department of Pediatrics, The University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA. mpourcyrous@utmem.edu
authors.forename: Massroor
authors.initials: M
authors.lastname: Pourcyrous
authors.forename: Henrietta S
authors.initials: HS
authors.lastname: Bada
authors.forename: Kari E
authors.initials: KE
authors.lastname: Blaho
authors.forename: Mildred M
authors.initials: MM
authors.lastname: Randolph
authors.forename: Helena
authors.initials: H
authors.lastname: Parfenova
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Mandrell
authors.forename: Kris
authors.initials: K
authors.lastname: Arheart
authors.forename: Sheldon B
authors.initials: SB
authors.lastname: Korones
authors.forename: Charles W
authors.initials: CW
authors.lastname: Leffler
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001160:Arterioles / Q000187:drug effects / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects; D002245:Carbon Dioxide / Q000097:blood; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D003042:Cocaine / Q000633:toxicity*; D000242:Cyclic AMP / Q000134:cerebrospinal fluid / Q000378:metabolism; D005260:Female; D006863:Hydrogen-Ion Concentration; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000503:physiopathology; D010100:Oxygen / Q000097:blood; D010313:Partial Pressure; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D013552:Swine
chemical_list: D002245:Carbon Dioxide; D000242:Cyclic AMP; D003042:Cocaine; D010100:Oxygen