Adenosine A(1) receptor mediated suppression of adrenal activity in near-term fetal sheep.

Activation of the hypothalamic-pituitary-adrenal (HPA) axis is a critical response to perinatal hypoxia. Recent data show that adenosine appears to inhibit baseline levels of fetal cortisol and to restrict the increase in ACTH and cortisol during moderate hypoxia. Because adenosine increases substantially during profound asphyxia, it is possible, but untested, that counterintuitively it might restrict the HPA response to more severe insults. It is unclear which receptors mediate the effects of adenosine on the HPA axis; however, adenosine A(1) receptor activation is important for adaptation to hypoxia. We therefore investigated whether adenosine A(1) receptor blockade modulates ACTH and cortisol levels in fetal sheep at 118 to 126 days gestation, randomly allocated to receive an intravenous infusion of either vehicle (vehicle-occlusion, n = 7) or 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, an A(1) receptor antagonist, DPCPX-occlusion, n = 7) infused 60 min before and during 10 min of umbilical cord occlusion, or infusion of DPCPX for 70 min without occlusion (DPCPX-sham, n = 6). Experiments were terminated after 72 h. Fetal ACTH levels increased significantly (P < 0.01) during occlusion, but not sham occlusion, and returned to baseline values by 60 min after occlusion. In the vehicle-occlusion group, fetal cortisol and cortisone plasma levels increased significantly (P < 0.05) 60 min after the occlusion and returned to baseline values by 24 h. In contrast, there was a marked increase in both fetal cortisol and cortisone during DPCPX infusion before occlusion to a level greater even than the maximum rise seen after occlusion alone. This increase was sustained after occlusion, with increased cortisol levels compared with occlusion alone up to 72 h. In conclusion, fetal cortisol concentrations are suppressed by adenosine A(1) receptor activity, largely though a direct adrenal mechanism. This suppression can be partially overcome by supraphysiological stimuli such as asphyxia.

Plasma adenosine levels and P-selectin expression on platelets in preeclampsia.

OBJECTIVE: To measure the correlation of plasma adenosine levels with platelet activation in women with preeclampsia. METHODS: Plasma adenosine concentration and expression of P-selectin, a marker for platelet activation, were measured in 18 normal pregnant women and 18 preeclamptic women. The effect of 8-sulfophenyltheophylline, an adenosine receptor blocker, on expression of P-selectin on platelets also was measured. RESULTS: Plasma adenosine level averaged 0.77 +/- 0.11 microM (standard error of the mean [SEM]) in women with preeclampsia, significantly higher than the mean level of 0.47 +/- 0.08 microM in women with normal pregnancies (P <.05). Expression of P-selectin on platelets averaged 7.8 +/- 1.2% in women with preeclampsia, also significantly higher than the mean level of 4.7 +/- 0.7% in normal pregnancy (P <.05). Adenosine receptor blockade significantly increased expression of P-selectin on platelets in women with preeclampsia by 26% (P <.05), which was significantly higher than the 13% increase of activation in those with normal pregnancies (P <.05). CONCLUSION: Adenosine is an established platelet activation suppressor. Increased plasma levels of adenosine in preeclampsia might partially compensate and tend to prevent further excessive platelet activation in women with preeclampsia.

Severity of hyperemesis gravidarum correlates with serum levels of reverse T3.

To investigate the possible physiological relevance of extra-thyroidal production of reverse T3 (rT3) in hyperemesis gravidarum, measurements of serum rT3, free T3 (FT3), free T4, (FT4), and nonesterified fatty acids (NEFA) were correlated with weight loss of hyperemetic women. All the thyroid hormones, NEFAs and weight loss were significantly higher in hyperemesis gravidarum than in control subjects, and also higher than in those with milder symptoms of morning sickness (p < 0.05). Elevations of FT3, FT4 and NEFAs correlated with the extent of weight loss, the latter taken as the index of the severity of hyperemesis gravidarum (p < 0.05). Only rT3 correlated with both weight loss and the rate of lipolysis, as reflected by elevations of NEFAs (p < 0.05). The data are consistent with a shift from T3 to rT3 as products of 5'-monodeiodination of thyroxine in hyperemesis gravidarum. Because reverse T3 is physiologically inactive a control mechanism may be postulated wherein T3 production is minimized, thereby reducing weight loss and lipolysis in patients with hyperemesis gravidarum.

Adaptation of laser-Doppler flowmetry to measure cerebral blood flow in the fetal sheep.

The purpose of this study was to devise a means to use laser-Doppler flowmetry to measure cerebral perfusion before birth. The method has not been used previously, largely because of intrauterine movement artifacts. To minimize movement artifacts, a probe holder was molded from epoxy putty to the contour of the fetal skull. A curved 18-gauge needle was embedded in the holder. At surgery, the holder, probe, and skull were fixed together with tissue glue. Residual signals were recorded after fetal death and after maternal death 1 h later. These averaged <5% of baseline flow signals, indicating minimal movement artifact. To test the usefulness of the method, cerebral flow responses were measured during moderate fetal hypoxia induced by giving the ewes approximately 10% oxygen in nitrogen to breathe. As fetal arterial PO(2) decreased from 21.1 +/- 0.5 to 10.7 +/- 0.4 Torr during a 30-min period, cerebral perfusion increased progressively to 56 +/- 8% above baseline. Perfusion then returned to baseline levels during a 30-min recovery period. These responses are quantitatively similar to those spot observations that have been recorded earlier using labeled microspheres. We conclude that cerebral perfusion can be successfully measured by using laser-Doppler flowmetry with the unanesthetized, chronically prepared fetal sheep as an experimental model. With this method, relative changes of perfusion from a small volume of the ovine fetal brain can be measured on a continuous basis, and movement artifacts can be reduced to 5% of measured flow values.

Plasma adenosine levels increase in women with normal pregnancies.

OBJECTIVE: The aim of this study was to investigate plasma adenosine levels during normal pregnancy and to evaluate the possible roles of platelet activation and 5'-nucleotidase as causes of changes in adenosine levels. STUDY DESIGN: We measured plasma adenosine levels, the platelet activation markers beta-thromboglobulin and platelet factor 4, and 5'-nucleotidase activity, which catalyzes dephosphorylation from adenosine monophosphate to adenosine, in 34 nonpregnant women and 34 women with normal pregnancies in the third trimester. RESULTS: The mean plasma adenosine level in pregnant women was 0.59 +/- 0.08 micromol/L (mean +/- SEM), which was significantly higher than that found in nonpregnant women (0.18 +/- 0.04 micromol/L; P <.01). In pregnant women plasma beta-thromboglobulin levels, platelet factor 4 levels, and 5'-nucleotidase activity were significantly higher than in nonpregnant women (P <.05). CONCLUSION: The increase of plasma adenosine may be attributed at least in part to platelet activation and an increase of 5'-nucleotidase activity during normal pregnancy. This increase may be an endogenous compensatory mechanism that diminishes platelet activation and maintains vessel integrity during normal pregnancy.

Application of laser Doppler flowmetry to measure cerebral microvascular perfusion in the fetal sheep.

Laser Doppler flowmetry (LDF) has been used to measure flow in various organs of the adult, but has not been applied to the mammalian fetus. The purpose of this study was to apply LDF to measure cerebral blood flow of the fetal sheep and to assess the possible errors and artifacts of the method caused by myometrial, fetal, and maternal movements. By three days after probe placement, the flow signal had decreased 55% from initial post surgical readings and thereafter it became stable. During fetal hypoxia, the signal increased 48% and during hypercarbia it increased 59%. After fetal death, the signal decreased to 48% of control level. After maternal death, it decreased to 9% and electrical zero could not be reached. LDF is useful to measure changes of fetal cerebral microvascular perfusion because it can provide continuous signals but care is required in data handling and probe fixation when used for the mammalian fetus.

Hyperthermia prevents metabolic and cerebral flow responses to hypoxia in the fetal sheep.

OBJECTIVE: Fetal brain temperature has been found to decrease during hypoxia, strongly suggesting a reduction in cerebral O2 consumption and increases in cerebral blood flow. These responses may protect the brain in part against hypoxic injury. This study was undertaken to examine whether these compensatory mechanisms are lost during fetal hyperthermia. METHODS: Intermittent fetal hypoxemia was induced by administering low-O2 gas mixtures to nine near-term ewes. Fetal brain and body core temperature responses were measured with and without fetal hyperthermia induced by circulating warm water through a plastic coil looped about the fetus in utero. RESULTS: In normothermic fetuses, fetal brain temperature relative to core decreased during a 30-minute period of hypoxia and then returned to normal during recovery. This response may be explained by a combination of cerebral hypometabolism and increased cerebral blood flow. However, in hyperthermic fetuses (intrauterine warming for 1 hour, raising body core and brain temperatures 0.66 +/- 0.06 and 0.61 +/- 0.10 C, respectively) a subsequent period of hypoxia no longer induced a reduction in brain temperature relative to body core. CONCLUSION: When temperature of the fetal sheep is elevated, as may occur with maternal fever, prolonged exercise, and elevated environmental temperatures, the fetal brain is less well protected against hypoxic injury.

Changes in fetal plasma adenosine and xanthine concentrations during fetal asphyxia with maternal oxygen administration in ewes.

In this study, we measured fetal plasma adenosine and xanthine concentrations during and after severe asphyxia, and investigated the key issues related to oxygen therapy. Asphyxia was induced by occluding the umbilical cord for 5 minutes in 6 fetal sheep with and without the administration of oxygen to the ewe. Plasma adenosine concentration increased significantly during cord occlusion in the all fetuses, and the differences between the values in the fetuses with and without maternal oxygen administration was not significant. By 30 minutes after cord release, plasma adenosine concentration in all fetuses had returned to levels similar to those at the start of the experiment. Plasma xanthine concentration also increased during cord occlusion in all fetuses. However, 30 minutes after cord release, plasma xanthine concentration had decreased significantly in fetuses without additional oxygen, while it did not change significantly in fetuses with maternal oxygen administration. Thus, we speculated that maternal oxygen administration before fetal asphyxia may not contribute to additional ATP stores in fetal organs and may produce oxygen free radicals following asphyxia.

Role of adenosine in regulation of brain temperature in fetal sheep.

OBJECTIVE: The purpose of this study was to test adenosine's possible suppression of heat production by the ovine fetal brain during acute hypoxia. STUDY DESIGN: Hypoxia was induced by occluding the umbilical cord for 5 minutes in 8 fetal sheep with and without an adenosine receptor blocker, theophylline, and fetal brain and core temperatures were recorded. RESULTS: In 8 untreated fetuses, cord occlusion induced severe but reversible hypoxemia (decrease in carotid arterial PO (2) from 23 +/- 1 to 5 +/- 1 mm Hg (P <.01), a 2.3-fold increase in plasma adenosine, and an increase in body core temperature of 0.19 degrees C +/- 0.03 degrees C (P <.01), yet brain temperature remained constant. However, after cord occlusion with prior and continuing administration of theophylline, brain temperature did not increase as hypothesized but rather decreased, suggesting marked reductions in cerebral metabolic rate. This response occurred despite similar degrees of hypoxemia and similar increases in plasma adenosine and body core temperature. CONCLUSION: We conclude that the temperature of the fetal ovine brain remains constant or decreases during severe reversible hypoxemia by mechanisms other than those dependent on adenosine.

Evidence for mechanisms of the acute-phase response to endotoxin in late-gestation fetal goats.

OBJECTIVE: The aim of this study was to evaluate the relationship between febrile response to fetal endotoxin administration and fetal plasma endogenous pyrogen, tumor necrosis factor-alpha, the possible putative pyrogen mediator prostaglandin E2, and the endogenous antipyretic arginine vasopressin in late-gestation pregnant goats. STUDY DESIGN: Changes in fetal core temperature, plasma tumor necrosis factor-alpha, prostaglandin E2, and arginine vasopressin levels were measured after administration of Escherichia coli endotoxin (70 microg/kg of fetal weight) to 10 fetal goats in late gestation. RESULTS: Fetal body temperature did not rise after endotoxin administration. Fetal plasma tumor necrosis factor-alpha and arginine vasopressin increased to 87.5 +/- 15.2 pg/mL and 25.1 +/- 4.8 pg/mL, respectively, after 1 to 2 hours (P < .05). Fetal plasma prostaglandin E2 levels did not change significantly throughout the study. CONCLUSION: The absence of a febrile response to endotoxin in late-gestation fetal goats is accompanied by a deficient responses in prostaglandin generation in the periphery and increased activity of the antipyrogen arginine vasopressin.

Brain temperature and metabolic responses during umbilical cord occlusion in fetal sheep.

The purpose of this study was to compare core body and brain temperatures after complete but intermittent occlusions of the umbilical cord. Thermocouple probes were placed in the parasagittal parietal cortex, ascending aorta, and jugular vein of eight near-term fetal sheep and in the maternal descending aorta. Three days later, after an initial control period, the umbilical cord was occluded for 5 min, followed by a 30-min recovery period, and this cycle was repeated 4 times. Temperature changes, blood gases, and plasma glucose, lactate and adenosine were measured. In the first occlusion period, body core temperature increased 0.12 degreesC over control, and then declined to baseline after cord release, and this pattern was repeated with subsequent occlusions. Brain temperature, however, did not increase in response to any of the cord occlusions. Plasma adenosine increased 2.4-fold during the first occlusion, but not during subsequent occlusions, despite a continuing pattern of constant brain temperature, a result which minimizes adenosine's importance as a continuing regulator of cerebral metabolism. We conclude that brain temperature fails to increase because of diminished heat production by the brain and increases in cerebral blood flow, responses which delay complete depletion of adenosine 5'-triphosphate stores in brain tissue.

Fetal plasma hypoxanthine level in growth-retarded fetuses before labor.

Hypoxanthine is one of the purine nucleotides and is presumed to accumulate during hypoxia and acidemia. It remains uncertain, however, whether plasma hypoxanthine concentration is a useful indicator of fetal asphyxia; and its relationship to other markers of fetal physiologic state is not clearly defined. The aim of this study was to evaluate whether the level of fetal plasma hypoxanthine is correlated with fetal hypoxia and acidosis in growth-retarded fetuses before the onset of labor. Cordocentesis was performed in 34 growth-retarded fetuses at 31-35 weeks' gestation for the measurement of umbilical venous plasma concentrations of hypoxanthine, hemoglobin and lactate concentrations, blood gases, and base deficit. Umbilical venous plasma hypoxanthine concentration was found to be increased significantly, in parallel with the degree of acidosis (r = -0.74, P < 0.05) and base deficit (r = -0.41, P < 0.05), but not to bear a significant relationship to the degree of hypoxemia or other measured variables. We conclude that increases in the plasma concentration of hypoxanthine may reflect an impaired physiological state in growth-retarded fetuses before labor.

Plasma adenosine responses during repeated episodes of umbilical cord occlusion.

OBJECTIVE: The purpose of this study was to measure changes in adenosine concentration in fetal arterial blood with use of an animal model of intermittent cord occlusion. Adenosine has been shown to be a potent vasodilator and inhibitor of metabolic processes in the adult, actions that help maintain a balance between oxygen supply and oxygen use. STUDY DESIGN: After a 30-minute control period, five chronically instrumented fetal sheep (125 +/- 2.2 days' gestation) were subjected to a 1-minute cord occlusion, followed by a 2-minute recovery. The occlusion-release cycle was repeated 20 times. Then, after a 1-hour interim, the same 20 cycles of occlusion were repeated. Fetal blood was collected during cord occlusion and 30 seconds after release. RESULTS: The plasma adenosine concentration averaged 0.82 +/- 0.19 mumol/L during the initial control period. The plasma adenosine concentration increased significantly to 1.06 +/- 0.23 mumol/L and 1.19 +/- 0.20 mumol/L during and after the fifth occlusion (p < 0.05 and 0.01, respectively). The plasma adenosine concentration reached a maximal level of 1.31 +/- 0.28 mumol/L after the twentieth cord occlusion. The concentration during the second group of occlusions was also higher than that during the control period (p < 0.05) but not higher than that during the first recovery period. By the conclusion of the study the plasma adenosine concentration had returned to 0.70 +/- 0.16 mumol/L. CONCLUSIONS: Plasma adenosine increases cyclically with intermittent cord occlusion in the near-term fetal sheep, but the response is attenuated or lost after 2 hours. These results together with those of earlier studies are consistent with a hypoxic protective action of adenosine that is largely restricted to early time periods of continuing intermittent hypoxia.

Improved method for single-bolus kinetic measurements using a noncleared reference indicator.

After intravenous injection of a tracer as a single bolus, its concentration decreases as it mixes with the plasma, disperses throughout the circulation, and enters body pools. Kinetic values that are dependent on early concentrations may be in considerable error because mixing is not instantaneous throughout the circulation, and this problem is particularly acute in the mammalian fetus, with its distinctive circulatory pattern. To minimize this error, a method was developed in which the noncleared reference tracer 125I-labeled albumin was injected together with a representative, rapidly cleared metabolite 14C-labeled palmitic acid, and the former was used to correct for mixing delay. A total of 19 disappearance curves were studied after intravenous injection into seven near-term fetal sheep. Kinetic values were calculated with and without correction for mixing delay. Taking account of mixing delay increased the calculated volume of distribution 41% [from 44 +/- 4 (SE) to 62 +/- 3 ml/kg, P < 0.001], increased plasma clearance rate 13% (from 41 +/- 2 to 47 +/- 1 ml-min-1.kg-1, P < 0.002), decreased the rate constant for irreversible loss 26% (from 1.05 +/- 0.07 to 0.78 +/- 0.04 min-1, P < 0.001), and increased the calculated effective half-life 26% (0.71 +/- 0.06 to 0.90 +/- 0.05 min, P < 0.001). Thus use of the additional reference marker significantly altered calculated results and provided values believed to more accurately describe rapid disappearance from the central mixing compartment into metabolic pools.

Engine and radiator: fetal and placental interactions for heat dissipation.

The 'engine' of fetal metabolism generates heat (3-4 W kg-1 in fetal sheep) which has to be dissipated to the maternal organism. Fetal heat may move through the amniotic/allantoic fluids to the uterine wall (conductive pathway; total conductance, 1.1 W degrees C-1 kg-1) and with the umbilical arterial blood flow (convective pathway) to the placenta. Because resistance to heat flow is larger than zero fetal temperature exceeds maternal temperature by about 0.5 degree C (0.3-1 degree C). Probably 85% of fetal heat is lost to the maternal organism through the placenta, which thus serves as the main 'radiator'. Placental heat conductivity appears to be extremely high and this may lead to impaired heat exchange (guinea-pig placenta). A computer simulation demonstrates that fetal temperature is essentially clamped to maternal temperature, and that fetal thermoregulatory efforts to gain thermal independence would be futile. Indeed, when the late gestational fetus in utero is challenged by cold stress, direct and indirect indicators of (non-shivering) thermogenesis (oxygen consumption, increase of plasma glycerol and free fatty acid levels) change only moderately. In prematurely delivered lambs, however, cold stress provokes summit metabolism and maximum heat production. Only when birth is imitated in utero (by cord clamping, external artificial lung ventilation and cooling) do thermogenic efforts approach levels typical of extra-uterine life. This suggests the presence of inhibitors of thermogenesis of placental origin, e.g. prostaglandins and adenosine. When the synthesis of prostaglandins is blocked by pretreatment with indomethacin, sheep fetuses react to intra-uterine cooling with vigorous thermogenic responses, which can be subdued by infusion of prostaglandin E2 (PGE2). Since the sheep placenta is known to produce sufficient amounts of PGE2, it seems that the placenta controls fetal thermogenic responses to some extent. This transforms the fetus into an ectothermic organism, and yet allows the newborn the full exploitation of thermoregulatory responses typical of endothermic animals.

Maternal theophylline administration and breathing movements in late-gestation human fetuses.

OBJECTIVE: To investigate the relation between maternal administration of theophylline and breathing movements during late gestation in human fetuses. METHODS: After a 1-hour control period, 17 women with normally grown fetuses at 33-38 weeks' gestation were given 400 mg of sustained-release theophylline orally. Maternal plasma theophylline and glucose concentrations were measured every hour, and the incidence of fetal breathing movements and breathing rates were measured continuously during the next 8 hours. Results were compared with those of a similar control group that did not receive theophylline. RESULTS: The maternal plasma theophylline concentration increased to detectable levels after 1 hour, reached therapeutic levels of 6.9 +/- 0.4 micrograms/mL (standard error of the mean) after 6 hours, and thereafter averaged 8.3 +/- 0.3 micrograms/mL, significantly higher than initial control values (P < .05). The mean glucose concentration was unchanged during the first 6 hours (79.2 +/- 1.1 mg/dL) and then decreased somewhat, averaging 75.8 +/- 1.1 mg/dL in the 7-8 hour period. The incidence of fetal breathing increased 26.4 +/- 1.9% after 5 hours and remained elevated during the next 3 hours at levels significantly higher than in the initial control period (P < .05) and higher than in the control group that did not receive theophylline. The mean hourly breathing rate averaged 40.9 +/- 1.3 breaths per minute after ingestion of theophylline, a nonsignificant change. CONCLUSIONS: Ingestion of theophylline by pregnant women in late gestation is associated with an increase in fetal breathing movements. Theophylline has been used widely in the management of asthma in pregnancy, and the assessment of fetal breathing movements is used routinely for evaluation of fetal status. Therefore, account must be taken of changes in breathing movements caused by maternal theophylline administration.

Suppressive action of endogenous adenosine on ovine fetal nonshivering thermogenesis.

Nonshivering thermogenesis is not initiated when the fetal sheep is cooled in utero but appears to require the removal of an inhibitor of placental origin at birth. To test whether adenosine is such an inhibitor, we examined the effect of the adenosine antagonist theophylline on the initiation of nonshivering thermogenesis during sequential cooling, ventilation, and umbilical cord occlusion in utero. Theophylline (18 mg/kg bolus and 0.6 mg.kg-1.min-1 thereafter) was infused for 90 min before and 90 min after cord occlusion. Theophylline enhanced the nonshivering thermogenic free fatty acid (FFA) and glycerol responses before cord occlusion, raising FFA concentrations 99% to 415 +/- 60 mueq/l (P < 0.01) and glycerol levels 87% to 526 +/- 135 mumol/l (P < 0.05). These FFA (P < 0.001) and glycerol (P < 0.05) concentrations were significantly greater than the corresponding period during the birth-simulation control. Umbilical cord occlusion did not alter FFA levels but induced a 41% rise in glycerol concentrations to 774 +/- 203 mumol/l (P < 0.05). The increases in nonshivering thermogenic indexes after the administration of the adenosine-receptor antagonist suggest that the quiescent state of ovine fetal brown adipose tissue may result, in part, from the tonic inhibitory actions of adenosine and that a decrease in adenosine concentrations enhances nonshivering thermogenesis. However, the further rise after umbilical cord occlusion suggests that at least one other inhibitor of placental origin inhibits nonshivering thermogenesis before birth.

Exogenous infusion of adenosine depresses whole body O2 use in fetal/neonatal sheep.

To examine a possible metabolic regulatory role for adenosine, infusions of adenosine and adenosine deaminase were given to 11 near-term fetal sheep during the simulation of birth in utero. Fetal arterial blood gases, the concentration of a number of metabolites, insulin, and whole body O2 consumption (VO2) were measured. After intrauterine ventilation and cord occlusion, fetal/neonatal VO2, measured by closed-circuit respirometry, averaged 11.0 +/- 1.1 (SE) ml (STPD).min-1.kg fetal wt-1 and plasma adenosine concentration ([Ado]) was 1.29 +/- 0.21 microM. Infusion of adenosine (1.5 mumol.min-1.kg-1) during the next 30-min interval increased [Ado] to 1.57 +/- 0.28 microM (not significant) and decreased VO2 to 7.7 +/- 0.5 ml.min-1.kg-1 (P < 0.05). The infusion reduced systolic blood pressure by 19% (P < 0.01) and diastolic blood pressure by 25% (P < 0.01) and increased heart rate by 19% (P < 0.01). At the highest rate of adenosine infusion studied (6 mumol.min-1.kg-1), [Ado] increased to 4.27 +/- 0.46 microM (P < 0.001) and VO2 did not measurably decline further, although there were further decreases in blood pressure and increases in heart rate. After administration of adenosine deaminase, [Ado] decreased to 0.58 +/- 0.13 microM (P < 0.05), whereas VO2 increased to 11.2 +/- 0.8 ml.min-1.kg-1 (P < 0.05); blood pressure and heart rate returned to basal levels. The dependence of VO2 on [Ado] is described by the relationship VO2 = 6.14 + 4.89 exp(-0.45[Ado]) (n = 144; r = 0.34; P < 0.001). Throughout the experiment, arterial O2 content and plasma glucose, lactate, glycerol, and fatty acid concentrations were normal or elevated, and, therefore, O2 lack and substrate deficiency were unlikely to have caused the reduction in VO2. We conclude that plasma adenosine may act as a messenger of energy status for the ovine fetus/neonate and may contribute thereby to a maintenance of a balance between O2 supply and O2 demand.

Autoradiographic analysis of expanded skeletal muscle in rats.

The use of tissue expanders in reconstructive surgery is now common. However, the physiologic mechanisms by which expansion is achieved are not well understood. A recent study demonstrated that rapid expansion of skeletal muscle is accompanied by an increase in the number of sarcomeres within a muscle fiber. This is in contrast to previous animal studies whose results suggested that synthesis of sarcomere units was limited to the perinatal period. To further investigate potential increases in sarcomeres and attempt to localize the active sites of sarcomere synthesis, labeled adenosine (3H) was injected into rats during the expansion of skeletal muscle. Adenosine was taken up by the muscle fibers and incorporated in the newly formed actin as part of light chains. An autoradiographic analysis of histologic sections of the expanded muscle demonstrated a statistically significant increase in radioactivity within the expanded muscle. The distribution of the radioactivity followed a proximal-to-distal gradient, with the proximal sections exhibiting more than 50 percent greater activity than the distal aspects. These data suggest a preference for sarcomere synthesis in the proximal portion of the expanding skeletal muscle. The significance of this finding is uncertain. However, we suspect that sarcomere synthesis is tension-dependent and likely to be related to local tension applied to a portion of the muscle fibers rather than to an anatomic site of preference.

Plasma endothelin-1 levels during asphyxia in the fetal goat.

The changes in fetal carotid arterial plasma levels of endothelin-1, catecholamines, PO2, PCO2 and pH were measured after intermittent repetitive umbilical cord occlusion in late gestation pregnant goats (n = 9). Endothelin-1 levels increased to 3.58 +/- 0.28 pg/ml immediately after the onset of fetal hypoxia, a level significantly higher than the respective values in the control period (p < 0.05). The elevation of fetal plasma endothelin-1 levels correlated inversely with carotid arterial PO2 (r = -0.41, p < 0.05) and pH (r = - 0.43, p < 0.05). The results suggest that increased endothelin-1 levels may contribute to the maintenance of the fetal circulation during fetal asphyxia.