Regional blood flow in asphyxiated fetuses with seizures.

OBJECTIVE: Our purpose was to determine ovine fetal regional blood flow changes during asphyxia of such severity that it results in seizures. STUDY DESIGN: Six ovine fetuses were exposed to severe asphyxia produced by maternal uterine artery occlusion for up to 90 minutes. Fetal blood pressure and heart rate, blood gases, acid base status, electrocorticogram, electromyogram and regional blood flow (radioactive microspheres) measurements were recorded. RESULTS: During the asphyxial insult pH fell from 7.39 +/- 0.01 (mean +/- SEM) to 6.99 +/- 0.01 at 60 minutes, base excess from 4 +/- 1 to -16 +/- 1 mEq/L, and oxygen content from 3.5 +/- 0.4 to 0.5 +/- 0.1 mmol/L (p < 0.05). There was no significant change in fetal heart rate or blood pressure. The fetal electrocorticogram was profoundly suppressed during asphyxia, and seizure activity began 50 +/- 19 minutes after the release of occlusion in all surviving animals. Blood flow increased to the heart and adrenals during asphyxia and decreased to spleen, gut, kidneys, and carcass (p < 0.05). There was no change in combined ventricular output and umbilical blood flow. There was no significant increase in total cerebral perfusion. CONCLUSION: When the ovine fetus is exposed to asphyxia of sufficient severity to produce neurologic damage (seizures), the pattern of redistribution of blood flow is comparable to the response to lesser asphyxia, except that a significant increase in total brain blood flow does not occur. This finding may have an important association with the development of long-term neurologic damage.

Hydralazine does not restore uterine blood flow during cocaine-induced hypertension in the pregnant ewe.

Cocaine abuse is widespread, and its use by the parturient has potential significant adverse effects in both the mother and the newborn. This study was undertaken in gravid ewes to determine the effects of treatment of cocaine-induced hypertension with hydralazine (Apresoline) on the maternal and fetal cardiovascular systems, catecholamine response, blood gas and acid-base status, and uterine blood flow (UBF). Twenty-one experiments were performed in 15 chronically instrumented ewes near term gestation. After a 30-min control period, cocaine was given intravenously to all ewes for 55 min to induce and maintain increased maternal mean arterial pressure (MMAP) and reduced UBF. The sheep were randomly assigned to receive either cocaine alone (n = 11, control group) or hydralazine (n = 10, treatment group), starting 15 min after the cocaine administration. Both drugs were discontinued 55 min after the start of the cocaine administration, followed by a 35-min recovery period. In the control group, cocaine administration resulted in a 31 +/- 13% (SD) increase in MMAP (P less than 0.05) and a 26 +/- 21% reduction in UBF (P less than 0.05). In the treatment group, the initial cocaine administration resulted in a similar increase in MMAP and decrease in UBF. Hydralazine therapy restored MMAP toward baseline after 20 min of administration, but UBF remained reduced (37 +/- 17%) throughout therapy (P less than 0.05) and recovery (18 +/- 13%) (P less than 0.05). The maternal heart rate increased maximally by 121 +/- 33% (P less than 0.05) after the administration of hydralazine, compared with a 14 +/- 21% increase (P less than 0.05) in the control group.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of mathematical indices of fetal heart rate variability with visual assessment in the human and sheep.

Mathematical indices for quantitation of fetal heart rate variability have been proposed by numerous authors, but there have only been infrequent attempts to determine which such indices correspond to the semi-subjective evaluation of variability observed by clinicians. We have previously examined most of the published indices by using them for calculation of the variability of sets of computer-generated numbers, and seeing if they fulfill certain criteria of validity. Two sets of indices (each measuring short-term and long-term variability) were selected as acceptable. Segments of fetal heart rate records from both humans and sheep, with a wide range of subjective variability, were used to compare the mathematically derived indices with the semi-subjective evaluation of three observers. The results show that the mathematical indices of short-term variability compare closely to its subjective evaluation of being present or absent. The long-term variability of indices also increase progressively with the observers' evaluations of increasing variability. The agreement among observers, measured by Cohen's kappa test, is generally "substantial", although for some indices the agreement was "moderate" to "almost perfect". We conclude that the two sets of indices examined do quantitate what is clinically regarded as fetal heart rate variability.

Mechanisms of asphyxial brain damage, and possible pharmacologic interventions, in the fetus.

An examination of the cellular and molecular mechanisms of neuronal cell damage may lead to the design of pharmacologic interventions during presumed or actual fetal asphyxia. Hypoxia-ischemia in its severest form results in insufficient adenosine 5'-triphosphate production. The most important effect of this is failure of adenosine 5'-triphosphate-dependent membrane functions, which maintain ionic homeostasis, that is, ionic pumping. There is K+ efflux and Na+ influx across the cell membrane, depolarization of the cell membrane, opening of the voltage-dependent calcium channels, and entrance of Ca++ into the cell. Cytosolic Ca++ is also increased by Ca++ efflux from the mitochondria and the sarcoplasmic reticulum. Ca++ is a toxin in high cytosolic concentrations; it activates phospholipases A and C, which cause membrane breakdown and release of free fatty acids, including arachidonic acid. The membrane is damaged, lysis occurs, and the neuron dies. High cytosolic Ca++ also causes release of excitatory amino acids (especially glutamate), which overwhelm the suppressant neurotransmitters, causing seizures, increased metabolism, and aggravation of the insufficient adenosine 5'-triphosphate availability. Thromboxane A2 is generated from arachidonic acid, increasing smooth muscle tone and thereby worsening the ischemia. Cyclooxygenase activity also results in formation of oxygen-free radicals that contribute to cell membrane damage, lysis, and death. Possibilities for pharmacologic interventions include (1) calcium channel blockers and antagonists, (2) excitatory neurotransmitter blockers, (3) oxygen-free radical scavengers (e.g., superoxide dismutase), (4) cyclooxygenase or prostaglandin synthesis inhibitors, and (5) seizure suppressants (e.g., phenobarbital). Some of these treatments have been shown experimentally to limit neuronal death in the adult and fetus, and after more investigative work they may be applicable to clinical practice.