Fetal swallowing: response to graded maternal hypoxemia.

A computer-based system, incorporating electromyography (EMG) and esophageal fluid flow measurement, was used to determine fetal breathing and swallowing responses to graded maternal hypoxemia. Five chronically prepared ewes with singleton fetuses at a gestational age of 130 +/- 2 (SE) days were subjected to successive 30-min periods of mild and moderate hypoxemia (inspired O2 fraction = 0.16 and 0.13, respectively). Mild and moderate maternal hypoxemia evoked significant reductions in fetal arterial PO2 (21 +/- 1 to 17 +/- 1 and 13 +/- 1 Torr, respectively), while fetal arterial pH, hematocrit, plasma osmolality, heart rate, and mean blood pressure did not change. Moderate hypoxemia was associated with significant increases in fetal plasma arginine vasopressin and renin activity and significant reductions from basal values in percent time breathing (53 +/- 4 to 25 +/- 12%), percent time swallowing (11.5 +/- 3.1 to 1.3 +/- 0.7%), and volume swallowed (21.3 +/- 2.1 to 4.8 +/- 2.7 ml/30 min). Fetal swallowing activity was better correlated with arterial PO2 (r = 0.8) than breathing activity (r = 0.45). We conclude that fetal swallowing is suppressed during mild and moderate hypoxemia. It is suggested that several sites and/or mechanisms may account for the hypoxemic inhibition of fetal activities.     

Maternal DDAVP-induced hyponatremia preserves fetal urine flow during acute fetal hemorrhage

Maternal administration of DDAVP induces maternal and fetal plasma hyponatremia, accentuates fetal urine flow, and increases amniotic fluid volume. Fetal hemorrhage represents an acute stress that results in fetal AVP secretion and reduced urine flow rate. In view of the potential therapeutic use of DDAVP for pregnancies with reduced amniotic fluid volume, we sought to examine the impact of maternal hypotonicity during acute fetal hemorrhage. Chronically catheterized pregnant ewes (130 +/- 2 days) were allocated to control or to DDAVP-induced hyponatremia groups. In the latter group, tap water (2,000 ml) was administered intragastrically to the ewe followed by DDAVP (20 microg bolus, 4 microg/h) and a maintenance intravenous infusion of 5% dextrose water for 4 h to achieve maternal hyponatremia of 10-12 meq/l. Thereafter, ovine fetuses from both groups were continuously hemorrhaged to 30% of estimated blood volume over a 60-min period. DDAVP caused similar degree of reductions in plasma sodium and osmolality in pregnant ewes and their fetuses. In response to hemorrhage, DDAVP fetuses showed greater reduction in hematocrit than control fetuses (14 vs. 10%). Both groups of fetuses demonstrated similar increases in plasma AVP concentration. However, the AVP-hemorrhage threshold was greater in DDAVP fetuses (22.5%) than in control (17.5%). Hemorrhage had no significant impact on plasma osmolality, electrolyte levels, or cardiovascular responses in either group of fetuses. Despite similar increases in plasma AVP, DDAVP fetuses preserved fetal urine flow rates, with values threefold those of control fetuses. These results suggest that under conditions of acute fetal stress of hemorrhage, maternal DDAVP may preserve fetal urine flow and amniotic fluid volume.     

The hemodynamic consequences of hemorrhage and hypernatremia in two amphibians

1. Graded hypovolemia was induced by hemorrhagic blood loss and graded hypernatremia by salt load in the toad, Bufo marinus, and the bullfrog, Rana catesbeiana. Maximal blood flow rates in the systemic arches and arterial and venous pressures were measured during activity after each stress. 2. Maximal blood flow rates in the B. marinus did not decline until blood loss exceeded 5% of initial body mass. In R. catesbeiana, losses of 2% initial body mass caused a decline (Fig. 1). 3. Maximal heart rates did not change with hemorrhage (Fig. 2). The decline in blood flow rates with hemorrhage was due to declining pulse volumes in both species (Fig. 3). 4. Arteriovenous pressure difference declined with hemorrhage in both species (Fig. 4). Peripheral resistance increased with hemorrhage in parallel with compromised blood flow rates (Fig. 5). 5. Plasma sodium concentration slightly increased with hemorrhage, while plasma protein concentration and hematocrit declined. Lymphatic compensation for hemorrhagic loss is indicated in both species (Fig. 6). 6. Induced hypernatremia compromised blood flow rates in both species at plasma sodium concentrations above 175 mM. The decline in flow rates was principally a result of a decrease in pulse volume, though maximal heart rates also declined (Figs. 2, 3, 7). 7. Induced hypernatremia had no effect on the arteriovenous pressure difference in B. marinus but caused it to decline in R. catesbeiana. Peripheral resistance increased in only B. marinus but not R. catesbeiana (Figs. 4, 5). Hematocrit did not change with salt load, indicative of a constant vascular volume.     

Protective effect of prenatal water restriction on offspring cardiovascular homeostasis in response to hemorrhage

We determined the cardiovascular and AVP responses of prenatally dehydrated (PreDehy) neonates to intravascular hemorrhage. Ewes with singleton fetuses were subjected to water restriction from 110 days of gestation to full term to achieve hypernatremia of 8-10 meq/l. Water and food were provided ad libitum to control ewes. After delivery, water and food were provided ad libitum to ewes from both groups, and newborns were allowed to nurse ad libitum. At 15 +/- 2 days of age, PreDehy and control lambs were prepared with bladder and femoral catheters and studied at 25 +/- 2 days of age. After a 2-h basal period, lambs were hemorrhaged to 30% of blood volume over 1 h (0.5% of blood volume/min) and monitored 1 h after hemorrhage. Neonatal arterial blood pressure was measured, and blood samples were collected. Basal plasma sodium levels, plasma osmolality, hematocrit, and mean arterial pressure were increased in PreDehy lambs compared with controls. Both groups had similar basal AVP levels and heart rate. In response to hemorrhage, all parameters remained significantly elevated in PreDehy lambs. Blood pressure decreased less in PreDehy lambs than in controls. The hemorrhage-AVP threshold (percent blood volume withdrawal at which plasma AVP values significantly increased) was markedly elevated (20 vs. 15%) and peak hemorrhage-induced AVP plasma levels were lower (5.6 +/- 1.5 vs. 10.1 +/- 1.5 pg/ml, P < 0.01) in PreDehy lambs than in controls. Thus offspring of dehydrated ewes demonstrate enhanced AVP secretory responses to hypotension. Despite potential long-term adverse effects of systemic hypertension, these results suggest a protective effect of prenatal water restriction on offspring cardiovascular homeostasis during blood volume reduction.     

Fetal sympathetic activity, transcutaneous PO2, and skin blood flow during repeated asphyxia in sheep

To improve detection of fetal distress, we examined whether increased fetal sympathetic activity during repeated episodes of asphyxia decreases skin blood flow, which can be monitored by recording transcutaneous PO2. Sympathetic activity was assessed by relating catecholamine concentrations in the fetal plasma to blood gas, acid-base, and heart rate variables which are commonly used to determine fetal distress. Fifteen experiments were conducted on 8 anaesthetised fetal sheep in utero between 125 and 145 days of gestation (term is at 147 days). They were subjected to 11 consecutive episodes of asphyxia of 30 (n = 3), 60 (n = 9), or 90 (n = 3) s over 33 min, achieved by arrest of uterine blood flow. Blood samples were drawn at 0, 33, and 60 min to determine arterial blood gases, acid base-balance, and concentrations of lactate, glucose, norepinephrine, and epinephrine. Fetal transcutaneous PO2, relative local skin blood flow, heart rate, arterial blood pressure, and arterial O2 saturation were recorded continuously. Fetal plasma concentrations of norepinephrine and epinephrine increased logarithmically as the duration of repeated asphyxia, anaerobic metabolism, and glucose concentrations increased, and as the mean O2 saturation, transcutaneous PO2, and local skin blood flow decreased. We conclude that during repeated episodes of asphyxia in fetal sheep near term, a significant increase in sympathetic activity can be detected indirectly by transcutaneous PO2 monitoring, because sympathetic activation reduces skin blood flow.     

Fetal asphyxia stimulates an increase in fetal plasma catecholamines and [Met]-enkephalin-arg6-phe7 in the late-gestation sheep fetus

We have investigated whether enkephalin-containing peptides and catecholamines are increased in fetal plasma during periods of reduced uterine blood flow which produce moderate fetal asphyxia (i.e. hypoxemia, hypercapnia and acidemia). Experiments (n = 16) were performed in 11 ewes between 121-139 days gestation. In 8 experiments a clamp placed around the common iliac artery of the ewe was adjusted to produce a 50% reduction in the partial pressure of arterial oxygen (PO2) in fetal plasma for 30 min between 121-125 days gestation (n = 4) and between 131-139 days gestation (n = 4). Control (n = 8) experiments were performed when the arterial clamp was not adjusted. There was no significant effect of asphyxia on fetal plasma noradrenaline concentrations before 126 days gestation. After 130 days gestation during asphyxia, fetal plasma noradrenaline concentrations increased significantly from 2.20 +/- 0.72 pmol/ml (-15 min) to 14.06 +/- 0.75 pmol/ml (+5 min). The fetal adrenaline response to asphyxia did not change with increasing gestational age and after 130 days gestation fetal plasma adrenaline increased significantly from 1.48 +/- 0.46 pmol/ml (-15 min) to 4.05 +/- 1.22 pmol/ml (+10 min). Met-enkephalin-arg6-phe7 immunoreactivity was measurable (25-117 pg/ml) in all pre-experimental fetal sheep plasma samples collected between 121-139 days gestation. There was no specific effect of asphyxia on fetal plasma [Met]-enkephalin-arg6-phe7-IR before 130 days gestation. However after 130 days gestation, there was a significant increase in fetal plasma (Met-enkephalin Arg-6-phe7-IR above baseline values, when compared to control experiments.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cardiovascular responses to acute, severe haemorrhage in fetal sheep

In adults, the responses to acute haemorrhage vary greatly depending on the amount of blood lost. While many studies have documented fetal responses to mild haemorrhage, fetal responses to severe haemorrhage are not known. In this study we examined the effect of acute, severe haemorrhage in fetal lambs. Despite the severity of haemorrhage, we found that mean arterial blood pressure was restored within 2 min, and heart rate was restored within 30 min. This restoration of blood pressure and heart rate was facilitated by an increase in peripheral vascular resistance mediated in part by secretion of catecholamines and plasma renin. In addition, about 40% of the shed blood volume was restored within 30 min by fluid from either the fetal interstitium or placenta. The PO2 of umbilical venous blood increased from 33 +/- 9 mmHg to 49 +/- 17 mmHg 2 min post-haemorrhage, and to 47 +/- 15 mmHg 30 min post-haemorrhage. However, this increase was not sufficient to offset the fall in both haemoglobin concentration and umbilical-placental blood flow, so that oxygen delivery decreased from 21.1 +/- 5.5 ml/min per kg to 9.1 +/- 5.2 ml/min per kg 2 min post-haemorrhage, and 14.1 +/- 9.2 ml/min per kg 30 min post-haemorrhage. Because of this decrease in oxygen delivery, oxygen consumption fell and a metabolic acidemia ensued. Nevertheless, oxygen delivery to the heart and brain was maintained because hepatic vasoconstriction diverted more of the well oxygenated umbilical venous return through the ductus venosus. Although the fetus was able to tolerate acute loss of 40% of blood volume, larger volumes of haemorrhage resulted in fetal death.     

Decline in lung liquid volume and secretion rate during oligohydramnios in fetal sheep

Reduced amniotic fluid volume often results in fetal lung hypoplasia. Our aim was to examine the effects of prolonged drainage of amniotic and allantoic fluids on lung liquid volume (Vl), secretion rate (Vs), and tracheal flow rate (Vtr) in fetal sheep. In five experimental animals, amniotic and allantoic fluids were drained from 107 to 135 days of gestation. The volume of fluid drained from the experimental animals was 411.8 +/- 24.4 ml/day (n = 140). In six control animals, amniotic fluid volume was 747.7 +/- 89.7 ml (n = 15). Wet and dry lung weights were 20-25% lower in experimental fetuses than in control fetuses. Fetal hemoglobin, O2 saturation, arterial PO2, pH, and hematocrit were unchanged by drainage. During the drainage period, Vl was up to 65% lower, Vs was up to 35% lower, and Vtr was up to 40% lower in experimental fetuses than in control fetuses. We conclude that prolonged drainage of amniotic and allantoic fluids decreases Vl, Vs, and Vtr in fetal sheep. These findings indicate that fetal lung hypoplasia associated with oligohydramnios may be the result of a prolonged reduction in Vl.     

Cardiac limitation to maximal oxygen transport and changes in components after jogging across the US.

Observations were made before and 3-5 days after prolonged endurance jogging an average of 42 miles/day, 6 days/wk for 2.5 mo by a young male adult who voluntarily initiated a run across the United States. Both arterial PO2 and lactic acid increased. In each instance, the first limitation in circulatory delivery of oxygen was a plateau in stroke volume and cardiac output. Afterward, pulse deficit and systemic arterial pressure fell with exercise and heart rate accelerated. Although there was no change in oxygen transport (Q X CAO2), a reduction in stroke volume was exactly balanced by a rise in arterial oxygen content. Vital capacity, residual volume, and total lung capacity and diffusion capacity for carbon monoxide, hematocrit, and red cell mass increased, while plasma volume diminished and heart size and total blood volume were unchanged.     

A compartmental model for oxygen transport in brain microcirculation in the presence of blood substitutes

A compartmental model is developed for oxygen (O(2)) transport in brain microcirculation in the presence of blood substitutes (hemoglobin-based oxygen carriers). The cerebrovascular bed is represented as a series of vascular compartments, on the basis of diameters, surrounded by a tissue compartment. A mixture of red blood cells (RBC) and plasma/extracellular hemoglobin solution flows through the vascular bed from the arterioles through the capillaries to the venules. Oxygen is transported by convection in the vascular compartments and by diffusion in the surrounding tissue where it is utilized. Intravascular resistance and the diffusive loss of oxygen from the arterioles to the tissue are incorporated in the model. The model predicts that most of the O(2) transport occurs at the level of capillaries. Results computed from the present model in the presence of hemoglobin-based oxygen carriers are consistent with those obtained from the earlier validated model (Sharan et al., 1989, 1998a) on oxygen transport in brain circulation in the absence of extracellular hemoglobin. We have found that: (a) precapillary PO(2) gradients increase as PO(2) in the arterial blood increases, P(50 p) (oxygen tension at 50% saturation of hemoglobin with O(2) in plasma) decreases, i.e. O(2) affinity of the extracellular hemoglobin is increased, the flow rate of the mixture decreases, hematocrit decreases at constant flow, metabolic rate increases, and intravascular transport resistance in the arterioles is neglected; (b) precapillary PO(2) gradients are not sensitive to (i) intracapillary transport resistance, (ii) cooperativity (n(p)) of hemoglobin with oxygen in plasma, (iii) hemoglobin concentration in the plasma and (iv) hematocrit when accounting for viscosity variation in the flow; (c) tissue PO(2) is not sensitive to the variation of intravascular transport resistance in the arterioles. We also found that tissue PO(2) is a non-monotonic function of the Hill coefficient n(p) for the extracellular hemoglobin with a maximum occurring when n(p) equals the blood Hill coefficient. The results of the computations give estimates of the magnitudes of the increases in tissue PO(2) as arterial PO(2) increases,P(50 p) increases, flow rate increases, hematocrit increases, hemoglobin concentration in the plasma increases, metabolic rate decreases, the capillary mass transfer coefficient increases or the intracapillary transport resistance decreases.     

Lung liquid secretion, flow and volume in response to moderate asphyxia in fetal sheep

The effects of moderate fetal asphyxia, induced by constriction of the maternal common internal iliac artery, on lung liquid secretion, tracheal fluid efflux and lung liquid volume have been investigated in unanaesthetized fetal sheep (111-142 days) in utero. During periods of fetal asphyxia the percent oxygen saturation, PO2, pH, and PCO2 of fetal carotid arterial blood changed from 57.2 +/- 1.3% (mean +/- SEM), 22.9 +/- 0.6 mmHg, 7.35 +/- 0.01 and 45.6 +/- 1.0 mmHg to 26.3 +/- 0.5% (P less than 0.001), 14.7 +/- 0.2 mmHg (P less than 0.001), 7.28 +/- 0.02, (P less than 0.001) and 47.8 +/- 0.4 mmHg (P less than 0.02), respectively. Fetal asphyxia, over 6 h, decreased the efflux of tracheal fluid from 7.07 +/- 0.47 ml/h to 3.97 +/- 0.36 ml/h (P less than 0.01) and, over 4 h, decreased the rate of lung liquid secretion from 9.42 +/- 1.76 ml/h to 4.91 +/- 1.54 ml/h (P less than 0.005), whereas it had no significant effect on lung liquid volume. The incidence of fetal breathing movements decreased from 52.9 +/- 2.5% to 22.6 +/- 3.5% during 6-h periods of fetal asphyxia. Thus, although fetal asphyxia decreased the net production of lung liquid, lung liquid volume was maintained probably, because the net efflux of fluid from the lungs via the trachea decreased to a similar extent.     

Subcutaneous PO2 as an index of the physiological limits for hemodilution in the rat.

This study was designed to test the hypothesis that changes in subcutaneous PO2 (PscO2) during progressive hemodilution will reliably predict a "critical point" at which tissue O2 consumption (VO2) becomes dependent on O2 delivery (QO2). Twelve pentobarbital-anesthetized male Sprague-Dawley rats (315-375 g) underwent stepwise exchange of plasma for blood (1.5 ml of plasma for each 1 ml of blood lost). The initial exchange was equal to 25% of the estimated circulatory blood volume, and each subsequent exchange was equal to 10% of the estimated circulatory blood volume. After nine exchanges, the hematocrit (Hct) fell from 42 +/- 1 to 6 +/- 1%. Cardiac output and O2 extraction rose significantly. PscO2 became significantly reduced (P < 0.05) after exchange of 45% of the blood volume (Hct = 16 +/- 1%). VO2 became delivery dependent when QO2 fell below 21 ml x min(-1) x kg body wt(-1) (mean Hct = 13 +/- 1%). Eight control rats undergoing 1:1 blood-blood exchange showed no change in PscO2, pH, HCO3(-), or hemodynamics. Measurement of PscO2 may be a useful guide to monitor the adequacy of QO2 during hemodilution.     

Fetal breathing, sleep state, and cardiovascular responses to graded anemia in sheep

Graded anemia was produced for 2 h in 10 unanesthetized fetal sheep by infusing plasma in exchange for fetal blood. This reduced the mean fetal hematocrits during the 1st h of anemia to 19.7 +/- 0.5% [control (C) = 28.2 +/- 1.1%] for mild anemia, 17.4 +/- 0.9% (C = 30.0 +/- 1.1%) for moderate anemia, and 15.1 +/- 1.0% (C = 29.2 +/- 1.3%) for severe anemia. The respective mean arterial O2 contents (CaO2) were 4.46 +/- 0.20, 3.89 +/- 0.24, and 3.22 +/- 0.19 ml/dl. Mean arterial PO2 was reduced significantly (by 2 Torr) only during moderate anemia, and mean arterial pH was decreased only during severe anemia. No significant changes occurred in arterial PCO2. Fetal tachycardia occurred during anemia. Mean arterial pressure was reduced by 2-3 mmHg during mild anemia; however, no significant blood pressure changes were observed for moderate or severe anemia. The incidence of rapid-eye movements and breathing activity was not affected by mild anemia, but the incidence of both was reduced significantly during moderate and severe anemia. It is concluded that 1) a reduction in CaO2 of greater than 2.48 +/- 0.22 ml/dl by hemodilution inhibits rapid-eye movements and breathing activity, and 2) the PO2 signal for inhibition does not come from arterial blood but from lower PO2 in tissue.     

Exercise responses in pregnant sheep: blood gases, temperatures, and fetal cardiovascular system

In an effort to examine the effects of maternal exercise on the fetus we measured maternal and fetal temperatures and blood gases and calculated uterine O2 consumption in response to three different treadmill exercise regimens in 12 chronically catheterized near-term sheep. We also measured fetal catecholamine concentrations, heart rate, blood pressure, cardiac output, blood flow distribution, blood volume, and placental diffusing capacity. Maternal and fetal temperatures increased a mean maximum of 1.5 +/- 0.5 (SE) and 1.3 +/- 0.1 degrees C, respectively. We corrected maternal and fetal blood gas values for the temperatures in vivo. Maternal arterial partial pressure of O2 (PO2), near exhaustion during prolonged (40 min) exercise at 70% maximal O2 consumption, increased 13% to a maximum of 116.7 +/- 4.0 Torr, whereas partial pressure of CO2 (PCO2) decreased by 28% to 27.6 +/- 2.2 Torr. Fetal arterial PO2 decreased 11% to a minimum of 23.2 +/- 1.6 Torr, O2 content by 26% to 4.3 +/- 0.6 ml X dl -1, PCO2 by 8% to 49.6 +/- 3.2 Torr, but pH did not change significantly. Recovery was virtually complete within 20 min. During exercise total uterine O2 consumption was maintained despite the reduction in uterine blood flow because of hemoconcentration and increased O2 extraction. The decrease of 3 Torr in fetal arterial PO2 and 1.5 ml X dl -1 in O2 content did not result in major cardiovascular changes or catecholamine release. These findings suggest that maternal exercise does not represent a major stressful or hypoxic event to the fetus.     

Redistribution of fetal circulation during repeated asphyxia in sheep: effects on skin blood flow, transcutaneous PO2, and plasma catecholamines

To improve the understanding of fetal responses to labour, we have ascertained whether reduced fetal skin blood flow after asphyxia reflects redistribution of the circulation, and if so, whether this can be detected by transcutaneous PO2 monitoring. We also studied the relation between plasma concentrations of catecholamines and organ blood flow. Eight experiments were conducted on 8 acutely-prepared fetal sheep in utero between 125 and 135 days of gestation. In each fetus 11 episodes of asphyxia were induced within 33 min by intermittent arrest of uterine blood flow for 90 s. The distribution of blood flow was measured before and after asphyxia (at 35.5 min) by the isotope-labelled microsphere method. Blood samples were drawn at 0, 33 (i.e. after 90 s recovery), and 40 min to determine blood gases, acid-base balance, and catecholamine concentrations. Fetal transcutaneous PO2, heart rate, arterial blood pressure, and arterial O2 saturation were recorded continuously. Repeated fetal asphyxia increased plasma catecholamine concentrations and caused a circulatory redistribution to the brain (181% change), adrenals (116% change), and lungs (105% change) at the expense of many peripheral organs, particularly of the skin (-61% change). The pattern of these changes was different from that observed by others in persistent hypoxia or asphyxia. The decrease in skin blood flow, which depressed transcutaneous PO2 and increased the arterial-transcutaneous PO2 difference, correlated with the decrease in blood flow to other peripheral organs and with an increase in blood flow to the brain stem. We conclude that reduced blood flow to the fetal skin after repeated episodes of asphyxia indicates circulatory redistribution, which can be detected by transcutaneous PO2 measurements. We suggest that monitoring of variables that depend on skin blood flow may improve fetal surveillance during complicated labour.     

Predict fetal brain PO2 during hypoxaemia and anemia in sheep

The mean brain PO2 of fetal sheep was calculated using equations based on the Krogh cylinder model of O2 diffusion. This analysis took into account the effect of red cell spacing on capillary PO2. Uncompensated changes in arterial O2 tension, the radius of the Krogh cylinder, and metabolic rate of brain tissue were predicted to affect mean brain PO2 more than uncompensated changes in brain blood flow or haemoglobin concentration. Under normal conditions (CaO2 = 7.42 ml/dl), the mean PO2 of the fetal brain was calculated to be about 12 mmHg. Hypoxaemia decreased the predicted mean O2 tension to 7.6 mmHg (CaO2 = 5.19 ml/dl), 5.0 mmHg (CaO2 = 4.11 ml/dl), and 4.3 ml/dl (CaO2 = 3.50 ml/dl). Isovolaemic anaemia reduced mean brain PO2 to 8.7 mmHg (CaO2 = 4.40 ml/dl), 8.3 mmHg (CaO2 = 3.94 ml/dl), and 7.3 mmHg (CaO2 = 3.19 ml/dl). During anaemia the increased distance between red cells was calculated to contribute significantly to brain hypoxaemia. A summary equation is presented which enables the investigator to estimate easily the mean PO2 of the fetal brain when several factors are changed from standard values.     

Reticulocyte changes after experimental anemia and erythropoietin treatment of horses.

Availability of recombinant human erythropoietin (EPO) has facilitated use to enhance red blood cell production, and therefore aerobic performance, in human and equine athletes. Recombinant human EPO promotes growth and differentiation of equine erythroid precursor cells, but in some horses repeat administration induces immune interference with endogenous EPO resulting in fatal anemia. Although blood reticulocyte parameters acquire unique changes in humans treated with EPO, with manual enumeration methods, horses were not considered to release reticulocytes from the bone marrow into circulation, even under severe erythropoietic stress. The goals of this study were to determine whether reticulocytes could be detected and characterized in horses that are anemic or have been treated with EPO using a modern hematology analyzer. Anemia was induced in six horses by removal of 30 ml of blood/kg of body wt over 24 h. After 28 days, the horses were treated twice with 55 U/kg of EPO (Eprex), and after 65 days they were treated thrice with 73 U/kg of EPO. Blood samples were analyzed with the ADVIA120 instrument every 3-5 days and bone marrow samples 7 days after anemia and EPO treatments. Analysis of blood reticulocyte parameters by ANOVA in a randomized complete block design determined that anemia and EPO induced significant (P < or = 0.05) increases in red cell distribution width and reticulocyte mean cell volume. Parameters changed only after EPO treatment were cellular hemoglobin concentration mean, mean cell volume, reticulocyte concentration, proportion of macrocytic reticulocytes, and reticulocyte cellular hemoglobin. These findings indicate that horses under erythropoietic stress and after EPO treatment release reticulocytes with unique characteristics into circulation.     

Homeostatic responses to water deprivation or hemorrhage in lactating and non-lactating Bedouin goats

Three lactating and three non-lactating black Bedouin goats were subjected to four days of water deprivation or to hemorrhage. Four days of water deprivation caused body wt losses of 32 and 23% and plasma volume losses of 30 and 34% in lactating and non-lactating goats respectively. Plasma osmolality increased 17 and 15% in lactating and non-lactating goats. Plasma arginine vasopressin concentration rose from about 5 pg/ml to a mean of 36 pg/ml. Plasma renin activity increased from about 0.7 ng/ml/hr to a mean of 3.45 ng/ml/hr in lactating and to 3.15 ng/ml/hr in non-lactating goats. At 4.5 hr post-rehydration plasma osmolality and plasma vasopressin concentration were back to normal in non-lactating, but still elevated in lactating goats. Plasma renin activity increased after rehydration. Rapid blood volume loss of 21-28% increased plasma vasopressin concentration to 16-35 pg/ml in non-lactating and to 70 or greater than 500 pg/ml in lactating goats. It is concluded that black Bedouin goats are well adapted to endure severe dehydration and rapid rehydration, but that they (especially lactating animals) react strongly to rapid volume depletion.     

The effect of acute hypoxaemia on ventricular function during beta-adrenergic and cholinergic blockade in the fetal sheep

The effect of acute hypoxaemia on right and left ventricular function was investigated in 8 fetal sheep (137-140 days gestation). Fetuses were instrumented with electromagnetic flow sensors on the ascending aorta and the main pulmonary artery. After 8 days recovery, hypoxaemia was achieved by reducing the maternal ewe's inspired O2 concentration to 13.1 +/- 1.5%. Control and hypoxaemic arterial blood values were pH 7.37 +/- 0.04 (SD) and 7.35 +/- 0.06, PCO2 48.0 +/- 2.8 and 47.6 +/- 5.1 mmHg, PO2 19.9 +/- 2.2 and 11.4 +/- 1.5 mmHg, haematocrit 37.5 +/- 1.2 and 39.5 +/- 2.2, respectively. Arterial pressure increased insignificantly with acute hypoxaemia (50.2 +/- 3.9 to 53.6 +/- 8.1 mmHg). Left and right ventricular performance was assessed by generating biventricular function curves relating stroke volume to mean atrial pressure. All function curves were composed of steep ascending and plateau limbs that intersected at a breakpoint. Comparing control and hypoxaemia function curves, the left ventricular stroke volume breakpoints were 0.79 +/- 0.20 and 0.78 +/- 0.21 ml/kg, respectively, while the right ventricular stroke volume breakpoints were 0.99 +/- 0.11 and 0.88 +/- 0.21 ml/kg (n.s.). In 4 fetuses, acute hypoxaemia was associated with significant increases in arterial blood pressure (P less than 0.05). In these fetuses, the right ventricular function curve was shifted significantly downward compared to the control right ventricular curve. When nitroprusside was given to these hypertensive fetuses to return blood pressure to control levels, the right ventricular function curve returned to baseline. We conclude that even under conditions of extreme hypoxaemia, ventricular function is well preserved in the normotensive fetal sheep. However, when increases in arterial pressure also accompany hypoxaemia, detectable changes in right ventricular function can be accounted for by changes in arterial pressure.