Maternal and fetal cardiovascular responses to methamphetamine in the pregnant sheep.
OBJECTIVE
Our purpose was to evaluate the maternal and fetal cardiovascular effects of maternally administered methamphetamine and to determine the extent of placental transfer.


METHODS
Seven near-term pregnant sheep were surgically instrumented to measure maternal and fetal blood pressure and heart rate, cardiac output, uterine flow, and umbilical flow. A single dose of methamphetamine 1 mg/kg was administered as a bolus to study maternal and fetal cardiovascular responses and placental transfer.


RESULTS
Maternal administration of methamphetamine caused increases in maternal blood pressure, heart rate, cardiac output, and systemic vascular resistance and decreased uterine blood flow. Peak maternal changes occurred within 10 minutes after methamphetamine administration and were near baseline by 180 minutes. Fetal blood pressure increased and returned slowly to baseline by 2 hours. After an initial decrease fetal heart rate increased above baseline values over the next 2 hours. Umbilical blood flow also decreased initially and then increased slightly. Fetal pH and PO2 tended to decrease. Maternal and fetal methamphetamine levels reached a maximum of 2.9 and 1.9 micrograms/ml, respectively. Rapid and significant placental transfer, delayed excretion into the amniotic fluid, and slow elimination from the maternal and fetal circulation were demonstrated.


CONCLUSIONS
Methamphetamine readily crosses the ovine placenta, producing significant and long-lasting maternal and fetal cardiovascular effects, which may have long-term consequences, especially if administered repetitively.
Stek
A M
AM
Department of Obstetrics and Gynecology, University of Cincinnati College of Medicine, OH 45267-0526.
Fisher
B K
BK
Baker
R S
RS
Lang
U
U
Tseng
C Y
CY
Clark
K E
KE
D000653:Amniotic Fluid / Q000737:chemistry / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects* / Q000196:embryology; D005260:Female; D005312:Fetal Blood / Q000737:chemistry; D005333:Fetus / Q000187:drug effects* / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects; D006340:Heart Rate, Fetal / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D008431:Maternal-Fetal Exchange / Q000187:drug effects; D008694:Methamphetamine / Q000493:pharmacokinetics / Q000633:toxicity*; D010100:Oxygen / Q000097:blood; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000187:drug effects* / Q000502:physiology; D012039:Regional Blood Flow / Q000187:drug effects; D012756:Sheep; D014599:Uterus / Q000098:blood supply / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects
D008694:Methamphetamine; D010100:Oxygen