Fetal oxygen uptake during uterine contractures

During contractures there are decreases in fetal oxygen tension. In order to determine if there are concomitant changes in fetal oxygen consumption, we calculated the latter during contractures from measurements of the umbilical blood flow and venous arterial oxygen content differences across the umbilical circulation. There were decreases in both the umbilical venous (from 8.8 +/- 0.2 (SEM) to 8.5 +/- 0.2 ml.dl-1, P less than 0.01) and umbilical arterial (5.9 +/- 0.1 to 5.2 +/- 0.2 mg.dl-1, P less than 0.001) oxygen contents. The umbilical venous-arterial oxygen content difference increased from 2.9 +/- 0.1 to 3.3 +/- 0.2 ml.dl-1 (P less than 0.005). Umbilical blood flow was 194.3 +/- 4.5 ml.min-1 kg-1 during relaxation and was unchanged during contractures. Fetal oxygen uptake increased from 5.7 +/- 0.3 to 6.5 +/- 0.4 ml.min-1 kg-1 (P less than 0.005) during contractures. This observation is consistent with our previous speculation that there is increased muscular activity of tone associated with contractures.     

The effect of vasopressin on fetal oxygenation in sheep

To examine the effects of vasopressin on fetal oxygenation the hormone was infused intravenously for 1 h (1.4-3.5 mU X min-1 X kg fetal weight-1) to chronically catheterized fetal lambs in utero (113-137 days gestation). Arterial pressure rose (48.3 to 59.6 mmHg) (1 mmHg = 133.322 Pa) and heart rate fell (185.3 to 141.0 beats/min) during the infusion. There was a significant increase in fetal arterial PO2 (20.0 to 23.1 mmHg) and significant declines in pH (7.414 to 7.381) and base excess. Umbilical blood flow rose, and the percentage increase in flow (23%) was identical to the proportional rise in arterial pressure. Accompanying the rise in umbilical blood flow was a rise in umbilical oxygen delivery. But as there was no change in fetal oxygen consumption, fractional oxygen extraction by the fetus fell significantly (0.31 to 0.25). These data indicate that the vasopressin-induced rise in fetal vascular PO2 results from an increase in umbilical oxygen delivery and concomitant fall in fractional extraction. Fetal vasopressin levels are greatly elevated during hypoxia, and under conditions of reduced oxygen supply, the effects of the hormone on umbilical oxygen delivery and vascular PO2 could have definite survival value.     

Prostaglandin production in the umbilical and uterine circulations in pregnant sheep at 129-136 days gestation.

Prostaglandins circulating in the maternal and foetal blood have been implicated in important physiological systems. These functions include foetal adrenal function, maintenance of patency of the ductus arteriosus, regulation of uterine and umbilical circulations, and labor and delivery type myometrial contractions. The placenta is a major site of prostaglandin production in pregnancy. Limited data are available which combine measurements of veno-arterial differences across the uterine and umbilical circulations with blood flow in these circulations to enable calculation of umbilical-placental and utero-placental production rates for the prostaglandins. In chronically instrumented pregnant ewes, between 129 and 136 days of gestation, prostaglandin F2 alpha(PGF2 alpha), 13, 14 dihydro-15-keto prostaglandin F2 alpha (PGFM), prostaglandin E2 (PGE2) were measured in the maternal carotid artery and uterine vein. Foetal PGE2, and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) (the major metabolite of prostacyclin) were measured in umbilical venous and foetal descending aorta arterial plasma. Umbilical and uterine blood flow were measured using the diffusion-equilibrium technique. Uterine blood flow was 1693 +/- 137 ml.min-1 (mean +/- SEM); uterine production rates were 480 +/- 88 ng.min-1 for PGF2 alpha, 517 +/- 144 ng.min-1 for PGFM, and 165 +/- 27 ng.min-1 for PGE2. Umbilical blood flow was 147 +/- 17 ml.min-1.kg-1 foetal body weight. Umbilical production rates into the foetal circulation were 11 +/- 2 ng.min-1.kg-1 for PGE2 and 6 +/- 2 ng. ng.min-1.kg-1 foetal body weight for PGI2.     

Acute anemic hypoxemia produces a transient depression in fetal respiratory activity

Isovolemic anemia was produced in 11 unanesthetized fetal sheep by withdrawal of blood and replacement with saline-dextran. Fetal hematocrit fell from 36 +/- 1 to 19 +/- 1% (SE). Fetal breathing movements, which were present during 34.4 +/- 5.5% of 3 h before the anemia, occurred 10.1 +/- 5.3, 14.8 +/- 4.4, and 27.1 +/- 6.7% in the 3 h following. The anemia caused a fall in arterial O2 concentration from 8.4 +/- 0.3 to 3.6 +/- 0.1 vol% and sagittal vein PO2 fell from 15.4 +/- 0.5 to 12.4 +/- 0.3 Torr. Cerebral metabolic rate during the period of anemia was 2.9 +/- 0.1 ml.100 g-1.min-1, which was unchanged from the control value of 3.0 +/- 0.2 ml.100 g-1.min-1. Sagittal vein PCO2 (54.2 +/- 1.4 Torr) remained constant after the fetus was made anemic. We conclude that respiratory activity in the sheep fetus is depressed by anemic hypoxemia but that the effect is transient.     

Oxygen delivery rate and sufficiency of oxygenation during ECMO in newborn baboons

Minimum acceptable O2 delivery (DO2) during extracorporeal membrane oxygenation (ECMO) remains to be defined in a newborn primate model. The right atrium, carotid artery, and femoral artery were cannulated, and the ductus arteriosus, aorta, and pulmonary artery ligated in neonatal baboons (Papio cynocephalus) under a combination of ketamine, diazepam, and pancuronium. The internal jugular vein was also cannulated retrograde to the level of the occipital ridge. We measured hemoglobin, pH, arterial and venous PO2 (both from the pump circuit and from the cerebral venous site), serum lactate and bicarbonate concentrations, and pump flow, and we calculated hemoglobin saturations, (DO2), O2 consumption (VO2), systemic O2 extraction, and cerebral O2 extraction. Six baboons were studied during each of two phases of the experiment. In the first, flow rates were varied sequentially from 200 to 50 ml.kg-1.min-1 with saturation maximized. In the second, flow was maintained at 200 ml.kg-1.min-1 and saturation was reduced sequentially from 100 to 38%. VO2 fell significantly below baseline at a flow rate of 50 ml.kg-1.min-1 and a DO2 of 8 +/- 2 (SE) ml.kg-1.min-1 in phase 1 and at DO2 of 12 +/- 5 in phase 2. Both systemic and cerebral O2 extraction rose significantly at a flow of 100 ml.kg-1.min-1 and DO2 of 17 +/- 4 ml.kg-1.min-1 in phase 1, whereas neither rose with decreasing DO2 in phase 2. In fact, cerebral extraction fell significantly DO2 of 16 +/- 6 ml.kg-1.min-1.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of hematocrit on cerebral blood flow with induced polycythemia

Cerebral blood flow (CBF) is lowered during polycythemia. Whether this fall is due to an increase in red blood cell concentration (Hct) or to an increase in arterial O2 content (Cao2) is controversial. We examined the independent effects of Hct and Cao2 on CBF as Hct was raised from 30 to 55% in anesthetized 1- to 7-day-old sheep. CBF was measured by the radiolabeled microsphere technique before and after isovolemic exchange transfusion with either oxyhemoglobin-containing erythrocytes (in 5 control animals) or with methemoglobin-containing erythrocytes (in 9 experimental animals). Following exchange transfusion in the control animals, Hct rose (30 +/- 1 vs. 55 +/- 1%, mean +/- SE), Cao2 increased (15.1 +/- 0.8 vs. 26.7 +/- 0.9 vol%), and CBF fell (66 +/- 9 vs. 35 +/- 5 ml X min-1 X 100 g-1). Because the fall in CBF was proportionate to the rise in Cao2, cerebral O2 transport (CBF X Cao2) was unchanged. Following exchange transfusion in the experimental animals, Hct rose (32 +/- 1 vs. 55 +/- 1%) but Cao2 did not change. Nevertheless, CBF still fell (73 +/- 4 vs. 48 +/- 2 ml X min-1 X 100 g-1) and, as a result, cerebral O2 transport also fell. The latter cannot be attributed to a fall in cerebral O2 uptake, as cerebral O2 uptake was unaffected during each of these conditions. Comparison of the two groups of animals showed that approximately 60% of the fall in CBF may be attributed to the increase in red cell concentration alone. It is probable that this effect is due largely to changes in blood viscosity.     

The effects of prostacyclin and thromboxane analogue (U46619) on the fetal circulation and umbilical flow velocity waveforms

In placental insufficiency and pre-eclampsia the relative production rates of prostacyclin and thromboxane by the placenta and umbilical vessels are altered and the Doppler umbilical flow velocity waveform shows a high resistance pattern. To investigate the control of umbilical placental blood flow by those eicosanoids either prostacyclin (10 micrograms/min), or the thromboxane analogue U46619 (10 ng/min) was infused into the distal aorta of 12 chronically catheterized fetal lambs at day 125. Thromboxane produced a rise in mean arterial pressure and a rise in the systolic diastolic ratio of the umbilical artery flow waveform (2.6 to 3.1; P less than 0.05). Umbilical blood flow did not change and there was no evidence of altered flow to other organs. Prostacyclin caused a fall in fetal mean arterial pressure and a decrease in the umbilical artery systolic diastolic ratio (2.9 to 2.4; P less than 0.05). Prostacyclin produced a three-fold increase in lung perfusion (and the onset of fetal breathing movements) and this was associated with a 90% reduction in muscle blood flow (hindlimb muscle flow reduced from 12.5 to 1.1 ml.min-1 100g-1; P less than 0.01). We conclude that the local release of thromboxane in the fetal placental vascular bed could account for the rise in systolic diastolic ratio seen in umbilical placental insufficiency.     

Fetal oxygen consumption and PO2 during hypercapnia in pregnant sheep

In 12 experiments on 9 chronically-cathetized pregnant sheep (116-143 days of gestation), fetal oxygen consumption, umbilical blood flow and blood gas values were measured before, during and after a 30-min period of hypercapnia, induced by having the ewes breathe 5% CO2 and 18% O2 in N2. During the large amplitude breathing stimulated by hypercapnia, O2 consumption increased by 21%, solely via a rise in O2 extraction. During apnoeic periods and low amplitude breathing in the hypercapnia period, oxygen consumption was not different from the control value, but fetal arterial and umbilical venous PO2 was significantly raised, by 3 and 6 mm Hg respectively. These changes were probably due to a Bohr shift in the maternal oxygen dissociation curve. During large amplitude breathing, PO2 fell to control levels, probably due in part to the increase in O2 extraction. It is concluded that vigorous breathing movements in the fetal sheep, such as those stimulated by hypercapnia, result to an increase in fetal O2 demands. Further, the work of such breathing is large, and probably equivalent to that performed in adults during vigorous hyperventilation against an inspiratory resistance.     

Decline in peripheral chemoreceptor excitatory stimulation during acute hypoxia in the lamb

Chemoreceptor function was studied in eight 2- to 3-day-old unanesthetized lambs to sequentially assess hypoxic chemoreflex strength during an 18-min exposure to hypoxia [inspired O2 fraction (FIO2) = 0.08]. The immediate ventilatory (VE) drop in response to five breaths of pure O2 was measured at 3, 7, and 15 min during hypoxia. Each lamb was studied again at 10-11 days of age. At 2-3 days of age VE increased, with the onset of hypoxia, from 658 +/- 133 (SD) ml.min-1 X kg-1 to a peak of 1,124 +/- 177 ml.min-1 X kg-1. A dampening of the VE response then occurred, with a mean decline in VE of 319 ml.min-1 X kg-1 over the 18-min hypoxia period. Each pure O2 test (Dejours test) resulted in an abrupt fall in VE (delta VEDejours). This VE drop was 937 +/- 163, 868 +/- 244, and 707 +/- 120 ml.min-1 X kg-1 at 3, 7, and 15 min of hypoxia, respectively. Comparing the three O2 tests, delta VEDejours was significantly decreased by 15 min, indicating a loss of about one-fourth of the O2 chemoreflex drive during hypoxia. Testing at 10-11 days of age revealed a smaller VE decline during hypoxia. O2 tests at the beginning and end of the hypoxic period were not significantly different, indicating a smaller loss of hypoxic chemoreflex drive in the more mature animals.(ABSTRACT TRUNCATED AT 250 WORDS)     

Vasodilator reserve in respiratory muscles during maximal exertion in ponies

Eight healthy adult grade ponies were studied at rest as well as during maximal exertion carried out with and without adenosine infusion (3 microM X kg-1 X min-1 into the pulmonary artery) on a treadmill to compare levels of blood flow in respiratory muscles with those in other vigorously working muscles and to ascertain whether there remained any unutilized vasodilator reserve in respiratory muscles of maximally exercising ponies. Radionuclide-labeled 15-micron-diam microspheres, injected into the left ventricle, were used to study tissue blood flows. During maximal exertion, there were increases above base-line values in heart rate (336%), mean aortic pressure (41%), cardiac output (722%), and arterial O2 content (56%). The whole-body O2 consumption was 123 +/- 11 ml X min-1 X kg-1, and the stride/respiratory frequency of the galloping ponies was 138 +/- 4/min. With adenosine infusion during maximal exertion, mean aortic pressure decreased (P less than 0.05), but none of the above variables was different from maximal exercise alone. During maximal exertion, blood flow in the adrenal glands, myocardium, respiratory, and limb muscles increased, whereas that in the kidneys decreased and the cerebral perfusion remained unaltered. With adenosine infusion during maximal exercise, renal vasoconstriction intensified, whereas adrenal and coronary beds exhibited further vasodilatation. During maximal exertion, blood flow in the equine diaphragm (265 +/- 36 ml X min-1 X 100 g-1) was not different from that in the gluteus medius (253 +/- 36) and biceps femoris (233 +/- 29); both are principal muscles of propulsion in the equine subjects) or the triceps brachii (227 +/- 26) muscles.(ABSTRACT TRUNCATED AT 250 WORDS)     

Oxygen supply and the placenta limit thermogenic responses in fetal sheep

The aim of this study was to assess the individual effects of cooling, increased oxygenation, and umbilical cord occlusion on nonshivering thermogenesis in utero. A cooling coil was placed around eight fetal sheep of 132-145 days gestation; thermistors were placed in the fetal esophagus and maternal iliac artery, vascular catheters and a tracheal catheter were inserted, and a snare was placed loosely around the umbilical cord. The next day cold water was circulated through the coil for 5 h. During the 1st h of cooling alone, fetal core temperature fell 2.79 degrees C, but indexes of brown fat activity increased only slightly. After ventilation with O2, plasma free fatty acid concentration (FFA) rose 7.4-fold to 244 +/- 42 mu eq/l, glycerol concentration rose fourfold to 376 +/- 85 microM, and the difference between brown fat and core temperature widened to 0.60 +/- 0.10 degrees C. Ventilation with N2-enriched air did not evoke similar responses. After snaring the umbilical cord while ventilation was continued, FFA rose to 554 +/- 95 mu eq/l, glycerol rose to 684 +/- 76 microM, and the temperature difference widened to 0.77 +/- 0.13 degrees C. Whole-body O2 consumption peaked at 19.6 ml.min-1.kg-1 of fetal tissue. We conclude that fetal thermogenic responses are limited in part by O2 delivery to brown fat and are augmented by occlusion of the umbilical cord.     

Acute anemia results in an increased glucose dependence during sustained exercise

We evaluated whether acute anemia results in altered blood glucose utilization during sustained exercise at 26.8 m/min on 0% grade, which elicited approximately 60-70% maximal O2 consumption. Acute anemia was induced in female Sprague-Dawley rats by isovolumic plasma exchange transfusion. Hemoglobin and hematocrit were reduced 33% by exchange transfusion to 8.6 +/- 0.4 g/dl and 26.5 +/- 1%, respectively. Glucose kinetics were determined by primed continuous infusion of [6-3H]glucose. Rates of O2 consumption were similar during rest (pooled means 25.1 +/- 1.8 ml.kg-1.min-1) and exercise (pooled means 46.8 +/- 3.0 ml.kg-1.min-1). Resting blood glucose and lactate concentrations were not different in anemic animals (pooled means 5.1 +/- 0.2 and 0.9 +/- 0.02 mM, respectively). Exercise resulted in significantly decreased blood glucose (4.0 +/- 0.2 vs. 4.6 +/- 0.1 mM) and elevated lactate (6.1 +/- 0.4 vs. 2.3 +/- 0.5 mM) concentrations in anemic animals. Glucose turnover rates (Rt) were not different between anemic and control animals at rest and averaged 58.8 +/- 3.6 mumol.kg-1.min-1. Exercise resulted in a 30% greater increase in Rt in anemic (141.7 +/- 3.2 mumol.kg-1.min-1) than in control animals (111.2 +/- 5.2 mumol.kg-1.min-1). Metabolic clearance rates (MCR = Rt/[glucose]) were not different at rest (11.6 +/- 7.4) but were significantly greater in anemic (55.2 +/- 5.7 ml.kg-1.min-1) than in control animals (24.3 +/- 1.4 ml.kg-1.min-1) during exercise.(ABSTRACT TRUNCATED AT 250 WORDS)     

Blood circulation and oxygen transport in the fetal guinea pig

Anaesthetized fetal guinea pigs near term were studied under conditions, where maternal placental flow of haemoglobin was maintained within the normal range. The rate of maternal fetal equilibration of intravenously injected 3H2O was found to be similar as in unanaesthetized animals (half time 4 min) indicating that fetal circulation was undisturbed under the present experimental conditions. Umbilical blood flow as determined by a modified 3H2O method was 0.13 ml . min-1 . g-1 of fetal body mass. Radioactive microspheres, injected into the fetal saphenous (jugular) vein, were distributed to the placenta, the lower body, the upper body and the lungs at a ratio of 31(47):27(39):30(6):12(8). From these data, cardiac output was calculated (0.38 ml . min-1 . g-1) and found to be almost equally distributed between the placenta, the lower body and the upper body. There was preferential streaming of the inferior vena caval blood to the upper body. There was no evidence for flow through a ductus venosus. The O2-saturation in the fetal carotid arterial blood was 59 +/- 4%. The O2-supply to the fetal tissues was estimated to be 3 times the oxygen consumption.     

Oxygen delivery and utilization in hypothermic dogs

Hypothermia produces a decrease in metabolic rate that may be beneficial under conditions of reduced O2 delivery (Do2). Another effect of hypothermia is to increase the affinity of hemoglobin for O2, which can adversely affect the release of O2 to the tissues. To determine the overall effect of hypothermia on the ability of the peripheral tissues to extract O2 from blood, we compared the response to hypoxemia of hypothermic dogs (n = 8) and of normothermic controls (n = 8). The animals were anesthetized, mechanically ventilated, and paralyzed to prevent shivering. The inspired concentration of O2 was progressively reduced until the dogs died. The core temperatures of the control and hypothermic dogs were 37.7 +/- 0.3 and 30.5 +/- 0.1 degree C, respectively (P less than 0.01). The O2 consumption (VO2) of the control dogs was significantly greater than that of the hypothermic dogs (P less than 0.05), being 4.7 +/- 0.4 and 3.2 +/- 0.3 ml X min-1 X kg-1, respectively. Hypothermia produced a left shift of the oxyhemoglobin dissociation curve (ODC) to a PO2 at which hemoglobin is half-saturated with O2 of 19.8 +/- 0.7 Torr (control = 32.4 +/- 0.7 Torr, P less than 0.01). The O2 delivery at which the VO2 becomes supply dependent (DO2crit) was 8.5 ml X min-1 X kg-1 for control and 6.2 ml X min-1 X kg-1 for hypothermia. The hypothermic dogs maintained their base-line VO2's at lower arterial PO2's than control.(ABSTRACT TRUNCATED AT 250 WORDS)     

Distribution of blood flow in muscles of miniature swine during exercise

The purpose of this study was to determine how the distribution of blood flow within and among the skeletal muscles of miniature swine (22 +/- 1 kg body wt) varies as a function of treadmill speed. Radiolabeled microspheres were used to measure cardiac output (Q) and tissue blood flows in preexercise and at 3-5 min of treadmill exercise at 4.8, 8.0, 11.3, 14.5, and 17.7 km/h. All pigs (n = 8) attained maximal O2 consumption (VO2max) (60 +/- 4 ml X min-1 X kg-1) by the time they ran at 17.7 km/h. At VO2max, 87% of Q (9.9 +/- 0.5 l/min) was to skeletal muscle, which constituted 36 +/- 1% of body mass. Average total muscle blood flow at VO2max was 127 +/- 14 ml X min-1 X 100 g-1; average limb muscle flow was 135 +/- 17 ml X min-1 X 100 g-1. Within the limb muscles, blood flow was distributed so that the deep red parts of extensor muscles had flows about two times higher than the more superficial white portions of the same muscles; the highest muscle blood flows occurred in the elbow flexors (brachialis: 290 +/- 44 ml X min-1 X 100 g-1). Peak exercise blood flows in the limb muscles were proportional (P less than 0.05) to the succinate dehydrogenase activities (r = 0.84), capillary densities (r = 0.78), and populations of oxidative (slow-twitch oxidative + fast-twitch oxidative-glycolytic) fiber types (r = 0.93) in the muscles. Total muscle blood flow plotted as a function of exercise intensity did not peak until the pigs attained VO2max, although flows in some individual muscles showed a plateau in this relationship at submaximal exercise intensities. The data demonstrate that blood flow in skeletal muscles of miniature swine is distributed heterogeneously and varies in relation to fiber type composition and exercise intensity.     

Right ventricular function in the hypoxaemic fetal sheep

Right ventricular function was investigated in seven fetal sheep (125-130 days gestation) hypoxaemic at a mean of 5 days postoperation, and were compared to nine normoxaemic fetal sheep of the same gestation. Arterial O2 and CO2 tensions, pH, and haematocrit values for the hypoxaemic and normoxaemic fetuses were 15.6 +/- 1.0 vs. 20.6 +/- 1.8 torr, 49.4 +/- 4.1 vs. 46.1 +/- 1.6 torr, 7.38 +/- 0.02 vs. 7.39 +/- 0.02, and 29 +/- 7.5 vs. 31 +/- 5.3%, respectively. Right ventricular output and stroke volume were similar in the two groups, 241 +/- 57 vs. 247 +/- 75 ml X min-1 X kg-1 and 1.5 +/- 0.4 vs. 1.5 +/- 0.4 ml X kg-1, respectively. Filling and afterload pressures were also similar in the hypoxaemic and normoxaemic fetuses with right atrial pressure of 3.0 +/- 1.0 vs. 3.7 +/- 1.2 mmHg, and arterial pressure of 42 +/- 5 vs. 43 +/- 4 mmHg, respectively. Ventricular function curves were produced by rapid withdrawal and re-infusion of fetal blood producing curves with a steep ascending limb and a plateau phase. The breakpoint joining the limbs of the control function curve for the hypoxaemic and normoxaemic fetuses were right atrial pressure 2.9 +/- 1.0 vs. 3.4 +/- 1.2 mmHg and a stroke volume of 1.5 +/- 0.5 vs. 1.5 +/- 0.4 ml X kg-1, respectively. Linear regression of stroke volume against arterial pressure from 30-90 mmHg during infusions of nitroprusside and phenylephrine at right atrial filling pressures greater than breakpoint was stroke volume = 0.018 ml X kg-1 X mmHg-1 arterial pressure +/- 2.25 ml X kg-1. This equation is not different from that calculated in normoxaemic fetuses, and demonstrates that the fetal right ventricle is quite sensitive to changes in arterial pressure. These data indicate that reduction in fetal oxygen content by an estimated 40% does not affect fetal right ventricular function.     

Behavioral activity during prolonged hypoxemia in fetal sheep

Experiments were conducted in unanesthetized, chronically catheterized pregnant sheep to determine the fetal behavioral response to prolonged hypoxemia produced by restricting uterine blood flow. Uterine blood flow was reduced by adjusting a vascular occluder placed around the maternal common internal iliac artery to decrease fetal arterial O2 content from 6.1 +/- 0.3 to 4.1 +/- 0.3 ml/dl for 48 h. Associated with the decrease in fetal O2 content, there was a slight increase in fetal arterial PCO2 and decrease in pH, which were both transient. There was an initial inhibition of both fetal breathing movements and eye movements but no change in the pattern of electrocortical activity. After this initial inhibition there was a return to normal incidence of both fetal breathing movements and eye movements by 16 h of the prolonged hypoxemia. These studies indicate that the chronically catheterized sheep fetus is able to adapt behaviorally to a prolonged decrease in arterial O2 content secondary to the restriction of uterine blood flow.     

Fetal breathing, sleep state, and cardiovascular responses to adenosine in sheep

The possibility that adenosine mediates hypoxic inhibition of fetal breathing and eye movements was tested in nine chronically catheterized fetal sheep (0.8 term). Intracarotid infusion of adenosine (0.25 +/- 0.03 mg.min-1.kg-1) for 1 h to the fetus increased heart rate and hemoglobin concentration but did not significantly affect mean arterial pressure or blood gases. As with hypoxia, adenosine decreased the incidence of rapid eye movements by 55% and the incidence of breathing by 77% without significantly affecting the incidence of low-voltage electrocortical activity. However, with longer (9 h) administration, the incidence of breathing and eye movements returned to normal during the adenosine infusion. Intravenous infusion of theophylline, an adenosine receptor antagonist, prevented most of the reduction in the incidence of breathing and eye movements normally seen during severe hypoxia (delta arterial PO2 = -10 Torr). It is concluded that 1) adenosine likely depresses fetal breathing and eye movements during hypoxia and 2) downregulation of adenosine receptors may contribute to the adaptation of breathing and eye movements during prolonged hypoxia.     

Low-dose dopamine hastens onset of gut ischemia in a porcine model of hemorrhagic shock.

Gut metabolism may become anaerobic before the whole body during progressive phlebotomy in dogs. Because dopamine has selective mesenteric vasodilator effects, we asked whether dopamine could delay onset of bowel ischemia during hemorrhagic shock. We studied whole body and gut O2 consumption (VO2) and O2 delivery (QO2) using progressive phlebotomy in anesthetized pigs. Nine pigs received a dopamine infusion of 2 micrograms.kg-1.min-1, whereas a control group of seven pigs received equivalent saline infusion. Onset of ischemia in whole body and gut was determined as critical O2 delivery (QO2c), the intersection point of biphasic regression on plots of VO2-QO2 relationships. Blood flow and O2 extraction were measured as mechanisms of gut ischemia for entire in situ small and large gut using a superior mesenteric venous fistula. Dopamine hastened onset of gut ischemia relative to onset of whole body ischemia (gut critical point in terms of whole body QO2 9.9 +/- 2.1 ml O2.kg-1.min-1, whole body QO2c 7.8 +/- 0.7 ml O2.kg-1.min-1, P less than 0.01). In contrast, onset of gut ischemia in control animals occurred at same time as onset of whole body ischemia (gut critical point in terms of whole body QO2 7.4 +/- 2.3 ml O2.kg-1.min-1, whole body QO2c 7.1 +/- 2.7 ml O2.kg-1.min-1, P = not significant). Hastening of onset of gut ischemia in dopamine-treated animals was associated with decreased ability of gut to extract O2. Low-dose dopamine was not protective against gut ischemia during shock but rather caused earlier onset of gut ischemia during hemorrhagic shock.     

Three months energy restricted diet does not reduce peripheral insulin resistance in newly diagnosed non insulin dependent diabetics

Sixteen newly diagnosed non insulin dependent diabetic patients were treated for 3 months with an individual energy restricted diet. The effect on weight, hyperglycaemia and insulin response to oral glucose was measured in all subjects, and in 7, peripheral insulin resistance was estimated using a hyperinsulinaemic glucose clamp at two insulin infusion rates (40 and 400 mU m-2 X min-1). After diet, fasting plasma glucose fell from 12.0 +/- 0.7 mmol/l (mean +/- SEM) to 7.4 +/- 0.5 mmol/l (P less than 0.001) and weight fell from 92.9 +/- 4.2 kg to 85.0 +/- 3.1 kg (P less than 0.001). The plasma insulin response to oral glucose was unchanged after diet therapy. Insulin induced glucose disposal (M) was also unaffected by diet at insulin infusion rates of 40 mU m-2 X min-1 (12.5 +/- 1.5 mumol X kg-1 X min-1 vs 15.7 +/- 1.6 mumol X kg-1 X min-1) and 400 mU m-2 X min-1 (49.5 +/- 2.7 mumol X kg-1 X min-1 vs 55.1 +/- 2.5 mumol X kg-1 X min-1). These results show that 3 months reduction of energy consumption with weight loss in newly diagnosed non insulin dependent diabetics improves B-cell responsiveness to glucose but has no effect on liver glucose output or on peripheral insulin action.