title: Fetal exposure to magnesium chloride-adenosine triphosphate (MgCl2-ATP) results in alterations in cerebral blood flow and a metabolic acidosis.
abstract: OBJECTIVE: Magnesium chloride-adenosine triphosphate (MgCl(2)-ATP), advocated as an adjunct treatment in shock resuscitation, might be useful for pregnant women who develop hypovolemia secondary to conditions such as placental abruption. The effects of this treatment on the fetus, however, have never been investigated. This study determined the direct, acute effects of MgCl(2)-ATP on fetal organ blood flow, hemodynamic measurements, and metabolic parameters before and after maternal hemorrhage. DESIGN: Experimental, randomized, nonblinded, control study. SETTING: Animal laboratory at a university research facility. SUBJECTS: This study was performed on 11 chronically instrumented, 123-day gestational age, pregnant ewes (term = 147 days) and their fetuses. INTERVENTIONS: Ewes were randomly allocated to either experimental (Expt, n = 5) or control (Cntl, n = 6) groups. After a 60-min baseline period, Expt fetuses received a 60-min iv infusion of MgCl(2)-ATP (150 &mgr;mole/hr each of MgCl(2) and ATP; at 3 mL/hr), and Cntl fetuses received an equivalent volume of 0.9% NaCl. After this infusion-only period, the infusion was continued, and ewes were intermittently bled over 1 hr for a total blood loss of 20 mL/kg (hemorrhage-plus-infusion period). After this, the infusions were continued, and ewes and fetuses were monitored for 1 additional hr (posthemorrhage period). Measurements: At the end of all periods, fetal and maternal blood pressures, blood gases, oxygen saturation, hemoglobin, serum electrolytes, and serum glucose concentrations were measured. At the end of the baseline, infusion-only, and hemorrhage-plus-infusion periods, fetal organ blood flows were determined using a fluorescent microsphere technique. Nonparametric statistics were used for comparisons (2-tailed, p </=.05). MAIN RESULTS: Maternal hemorrhage caused maternal hypotension, resulting in a decrease in fetal oxygen content and an increase in fetal hemoglobin and glucose concentrations. The changes were similar in both groups. In both groups, a progressive fetal metabolic acidosis developed during the hemorrhage period and it continued through the posthemorrhage period. This metabolic acidosis was more severe in the Expt fetuses and appeared to have started during the infusion-only period. There were no fetal deaths in either group. In the Cntl fetuses, there were increases from baseline after the hemorrhage-plus-infusion period in fetal adrenal (71%), brain (89%), and thymus (18%) blood flow and a decrease in muscle (-28%) blood flow. In the Expt fetuses, there were increases during the infusion-only period in adrenal (332%), myocardial (142%), and pancreatic (219%) blood flow and decreases in kidney (-25%) and skin (-75%) blood flow. These changes persisted during the hemorrhage-plus-infusion period. Most strikingly, regional cerebral blood flow in the Expt fetuses did not increase from baseline in any of the 10 brain areas sampled during the infusion-only period or following maternal hemorrhage. In Cntl fetuses, however, there was increase in blood flow in all 10 brain areas sampled following maternal hemorrhage. CONCLUSIONS: In healthy fetuses, direct MgCl(2)-ATP exposure caused metabolic acidosis and a redistribution of cardiac output to different organs. When the MgCl(2)-ATP fetuses were then subject to the effects of maternal hemorrhage, the expected increase in cerebral blood flow was not observed. Although an earlier study suggests that ATP may be beneficial to stressed fetuses when administered to mothers in labor, the direct effect of MgCl(2)-ATP appears to be potentially harmful by producing an acidosis and altering the normal fetal cerebral blood flow response to maternal hemorrhage.
authors.affiliation: Department of Clinical Sciences (Dr. Moon), and the Laboratory for Pregnancy and Newborn Research (Drs. Ramsay, Fecci, and Nathanielsz), College of Veterinary Medicine, Cornell University, Ithaca, New York.
authors.forename: Paula F.
authors.initials: PF
authors.lastname: Moon
authors.forename: Margaret M.
authors.initials: MM
authors.lastname: Ramsay
authors.forename: Peter E.
authors.initials: PE
authors.lastname: Fecci
authors.forename: Peter W.
authors.initials: PW
authors.lastname: Nathanielsz