Increased regional myocardial blood flows and oxygen deliveries during hypoxemia in lambs

Newborn humans may develop myocardial dysfunction in conjunction with severe birth asphyxia. Subendocardial or papillary muscle ischemia appears to be the basis for the myocardial dysfunction, yet patent coronary arteries have been demonstrated in the nonsurvivors. The asphyxiated newborns also have experienced hypoxemia, which has been suggested as the cause of myocardial ischemia. This study was designed to determine the relationship between reduced aortic blood oxygen content and blood flow as well as oxygen delivery within different regions of the heart. Three days after surgery, we measured blood flow and oxygen delivery to the free walls and papillary muscles of the right and left ventricles, the ventricular septum, and the atria in 10 lambs, during 20-min periods in 8-10% and 5-6% environmental oxygen concentrations. In each region of myocardium, blood flow increased linearly as the aortic blood oxygen content decreased. The slopes of the regression lines were similar for each region of ventricular myocardium. Atrial myocardial blood flow also increased as a linear function of the reductions in aortic blood oxygen content, but at a slower rate than in the ventricular regions. Hypoxemia was associated with increased oxygen delivery in each region of myocardium, but the two variables were not related in a linear or quadratic fashion. The results demonstrate that isolated hypoxemia is associated with increased blood flow and oxygen delivery in the free walls and papillary muscles of the right and left ventricles, the ventricular septum, and the atria.     

Nicotine delays arousal during hypoxemia in lambs

A decreased ability to arouse from sleep in response to arterial hypoxemia may lead to severe asphyxia and has been proposed as a mechanism of sudden infant death syndrome. Based on previous observations that nicotine exposure, a major environmental risk factor for sudden infant death syndrome, may impair hypoxic defense in neonates, we hypothesized that a short-term infusion of nicotine could impair hypoxic arousal through interference with oxygen-sensing mechanisms. Seven chronically instrumented unanesthetized lambs were studied at the age of 4.6 +/- 1.3 d during normoxia and acute hypoxia (0.1 fraction of inspired oxygen) for 5 min. Ventilation, transcutaneous Hb oxygen saturation, blood pressure, heart rate, and time to arousal were compared during a control saline infusion and during a 0.5 microg x kg(-1) x min(-1) nicotine infusion. Activity states, i.e. wakefulness and quiet sleep as well as arousal, were defined by EEG, nuchal electromyogram, and electrooculogram. Each lamb acted as its own control. Arousal from quiet sleep occurred significantly later during nicotine infusion compared with control (177 +/- 93 versus 57 +/- 41 s, p < 0.01) and at a lower transcutaneous Hb oxygen saturation (60 +/- 12 versus 79 +/- 12%, p < 0.01) (paired t test). The ventilatory response to hypoxia in wakefulness was similar during both conditions but was significantly attenuated in quiet sleep during nicotine infusion (p < 0.001, 2-way ANOVA repeated-measures design). Blood pressure and heart rate responses were similar during both conditions. These results suggest that a brief nicotine exposure blunts oxygen sensitivity in young lambs, a finding of potential relevance for sudden infant death syndrome.     

Ductus venosus flow velocity in newborn lambs during increased pulmonary artery pressure

The aim of the present study was to assess with ultrasound the ductus venosus flow velocity in newborn lambs with increasing pulmonary artery pressures and to evaluate whether this is a useful method to detect elevated pulmonary artery pressure. The ductus venosus flow velocity was studied with pulsed-wave Doppler echocardiography in nine newborn lambs < or = 30 h old. The lambs were anesthetized, mechanically ventilated, and instrumented to measure mean airway pressure and pulmonary artery and arterial blood pressures. A vascular occluder was placed around the main pulmonary artery. With mean pressures ranging from 20 to 50 mm Hg in the pulmonary artery, the ductus venosus flow velocity was examined. In seven lambs, the mean portal pressure and central venous pressure were also measured. With a stepwise increase in the pulmonary artery pressure, the minimum ductus venosus flow velocity during atrial systole decreased to a reversed flow, and the duration of this reversed flow component increased. The systolic forward peak flow velocity signal also gradually decreased. No changes were detected in the mean central venous or in the portal pressure with increasing pulmonary artery pressure or changes in ductus venosus flow. The flow velocity in the ductus venosus, which is higher than in other precordial veins, shows a reduction and even reversal of the nadir and an increase of the duration of reversed flow during atrial systole as a response to increased pulmonary artery pressure. Thus, Doppler ultrasound of the ductus venosus flow velocity may be a useful noninvasive diagnostic supplement to detect pulmonary hypertension of the newborn.     

Arousal from sleep during rapidly developing hypoxemia in lambs

Arousal is an important protective response that may prevent severe hypoxemia and death during sleep. However, very little is known about arousal from sleep in response to respiratory stimuli in newborns. Experiments were therefore done to investigate the arousal response from sleep to rapidly developing hypoxemia in eight lambs. Each lamb was anesthetized and instrumented for recordings of electrocorticogram, electrooculogram, nuchal and diaphragm electromyograms, and measurements of arterial hemoglobin oxygen saturation. A tracheotomy was done and a tracheostomy tube placed in the trachea so that the fraction of inspired oxygen could be changed quickly. No sooner than 3 days after surgery, measurements were made in quiet sleep and active sleep (AS) during 30-s control periods when the animals were breathing 21% oxygen and during experimental periods of hypoxemia when the animals were breathing either 10, 5, or 0% oxygen in nitrogen. During quiet sleep, arousal occurred at similar arterial hemoglobin oxygen saturations (81 +/- 6% on 10% O2, 80 +/- 5% on 5% O2 and 83 +/- 5% on 0% O2) suggesting that arousal was independent of the rate of change of arterial oxygen. However, during AS arousal occurred at different arterial hemoglobin oxygen saturations (76 +/- 6% on 10% O2, 55 +/- 11% on 5% O2, and 44 +/- 17% on 0% O2) suggesting that arousal was dependent on the rate of change of arterial oxygen. During some epochs of AS, electrocortical signs of cerebral hypoxia and primary apnea occurred before arousal. These data provide evidence that arousal from quiet sleep in response to hypoxemia occurs once an arousal threshold has been reached.(ABSTRACT TRUNCATED AT 250 WORDS)     

Factors controlling aldosterone secretion during hypoxemia in fetal lambs

Factors modulating the fetal aldosterone response to hypoxemia were studied in three groups of chronically catheterized fetal lambs between 131 and 143 days of gestation (term, 145 days). One group (control group) received an infusion of 5% dextrose in water; the second group (captopril-treated group) was given captopril, an inhibitor of angiotensin-converting enzyme; the third group (captopril plus dexamethasone-treated group) received dexamethasone in addition to captopril. In all groups of fetuses, hypoxemia was associated with a significant increase in plasma K+ concentration (+0.7 +/- 0.1 meq/liter). In control fetuses, changes in plasma aldosterone concentration during hypoxemia correlated closely with changes in plasma K+ concentration r = 0.79; P less than 0.001) and with changes in plasma angiotensin II concentration (r = 0.77; P less than 0.001). In the captopril-treated fetuses, the rise in plasma aldosterone concentration during hypoxemia correlated closely with plasma K+ (r = 0.79; P less than 0.001) but not with plasma angiotensin II values (r = 0.17). No significant correlation was found between percent changes in maternal aldosterone and percent changes in fetal aldosterone during hypoxemia and following recovery (r = 0.36; P greater than 0.1) in captopril-treated fetuses. Administration of dexamethasone to fetuses receiving captopril completely inhibited the rise in plasma aldosterone associated with hypoxemia. Taken together, the present results suggest that the rise in plasma aldosterone during hypoxemia is not related to the level of activity of the renin-angiotensin system but depends probably on the increased secretion of adrenocorticotrophin by the fetus.(ABSTRACT TRUNCATED AT 250 WORDS)     

Respiratory water loss and oxygen consumption in newborn infants during phototherapy

Respiratory water loss was measured together with oxygen consumption (VO2) and carbon dioxide production (VCO2) in 11 full-term and eight preterm infants (mean gestational age 34 weeks, range 31-36 weeks) before and during 1 h of phototherapy. The method for determination of respiratory water loss, VO2 and VCO2 was based on an open flow-through system with a mass spectrometer for measurement of gas concentrations. All infants were studied naked in an incubator with an ambient relative humidity of 50% and with a controlled environment with respect to temperature and air velocity. The infants were calm during the measurements. Before phototherapy, in term infants respiratory water loss was 4.4 (SD 0.7) mg/kg min and VO2 5.9 (0.9) ml/kg min and in preterm infants respiratory water loss was 4.7 (0.8) mg/kg min and VO2 6.1 (0.8) ml/kg min. No significant difference was found between values obtained during or after 1 h of phototherapy and those obtained before.     

Nitric oxide synthesis inhibition during cerebral hypoxemia and reoxygenation with 100% oxygen in newborn pigs

The objective of our study was to evaluate the effects of N(sigma)-nitro-L-arginine methyl ester (L-NAME), an inhibitor of the nitric oxide (NO) pathway, on cerebral microcirculation during hypoxemia and reoxygenation with 100% oxygen in newborn pigs. Twenty-two pigs were randomized to hypoxemia [inspired fraction of oxygen (FIO(2)) 0.08; 20 min] and reoxygenation (FIO(2) 1.0; 60 min) or normoxia. The hypoxemic animals were further randomized to receive either an intravenous bolus injection of 5 mg/kg L-NAME (n = 8) or a corresponding volume of isotonic saline (n = 8) 30 min before the onset of hypoxemia. The normoxemic group (n = 6) received the same pretreatment with L-NAME. Cerebral hemodynamics were assessed by laser Doppler flowmetry and intracranial pressure monitoring. The cerebral NO concentration was continuously measured using an electrochemical sensor. Pretreatment with L-NAME resulted in a more severe systemic hypotension and reduced cerebral microcirculation during the period of hypoxemia compared with the saline/hypoxemia group. NO synthesis inhibition during reoxygenation with 100% oxygen, however, blunted the increase in NO concentration (p < 0.05) without reduction of cerebral blood flow and cerebral perfusion pressure. In conclusion, in this newborn pig model, pretreatment with a bolus infusion of L-NAME induced severe hypotension and reduced cerebral microcirculation during hypoxemia. However, it appears to have no significant adverse effect on cerebral hemodynamics during the period of reoxygenation with 100% oxygen. This deleterious effect during hypoxemia limits the use of L-NAME as a preventive drug but suggests beneficial effects during reoxygenation with 100% oxygen.     

Respiratory response to adenosine in newborn lambs is modified by hypoxemia and by heat stress

A study was made to determine whether adenosine is involved in the regulation of breathing and whether the respiratory response to injections of adenosine and its analogue L-PIA (phenylisopropyl adenosine) is modified by moderate hypoxemia or by heat stress. Unanesthetized lambs with chronically implanted catheters were used for the investigation. Intravenous injections of adenosine caused an increase in the rate of breathing lasting for 5-30 s, except during heat stress, when the rate of breathing decreased. Injection of L-PIA also increased the rate of breathing, but the effects lasted longer than after injection of adenosine. During heat stress the response to injection of L-PIA varied. Both the arterial blood pressure and heart rate decreased transiently after intravenous injection of adenosine or L-PIA, while the central venous pressure increased. Adenosine might thus be part of a positive feedback system that stimulates breathing under normal environmental conditions with or without moderate hypoxemia. The respiratory responses to injection of adenosine during heat stress are different, which might indicate that under this condition the effects of adenosine on breathing are modified by its influence on temperature control.     

Comparative effects of metabolic acidemia and hypoxemia on cardiac output and regional blood flows in unanesthetized newborn lambs

We studied the comparative effects of HCl-induced metabolic acidemia (pH = 7.11 +/- 0.03, mean +/- SE) and hypoxemia (PO2 = 28 +/- 1 torr) on cardiac output and regional blood flows in newborn lambs 3 days after the surgical placement of catheters in the left atrium and aorta and pacing wires on the left atrium. Cardiac output decreased by 49 +/- 6% during metabolic acidemia in contrast to the 12 +/- 2% increase during hypoxemia. The adrenal glands and the diaphragm were the only organs that received increased blood flows during acidemia and hypoxemia. Cerebral and myocardial blood flows decreased during acidemia but increased during hypoxemia. Blood flows decreased to the carcass and gastrointestinal tract during acidemia but did not change significantly during hypoxemia. Renal and splenic blood flows decreased during both stresses, but the reductions were more severe during acidemia. The changes in regional blood flows were not a passive result of the respective changes in cardiac output. HCl-induced metabolic acidemia and hypoxemia each result in significant redistributions of available blood flows which are quantitatively and qualitatively different from each other.     

Purine and pyrimidine metabolism and electrocortical brain activity during hypoxemia in near-term lambs

Insufficient cerebral O(2) supply leads to brain cell damage and loss of brain cell function. The relationship between the severity of hypoxemic brain cell damage and the loss of electrocortical brain activity (ECBA), as measure of brain cell function, is not yet fully elucidated in near-term newborns. We hypothesized that there is a strong relationship between cerebral purine and pyrimidine metabolism, as measures of brain cell damage, and brain cell function during hypoxemia. Nine near-term lambs (term, 147 d) were delivered at 131 (range, 120-141) d of gestation. After a stabilization period, prolonged hypoxemia (fraction of inspired oxygen, 0.10; duration, 2.5 h) was induced. Mean values of carotid artery blood flow, as a measure of cerebral blood flow, and ECBA were calculated over the last 3 min of hypoxemia. At the end of the hypoxemic period, cerebral arterial and venous blood gases were determined and CSF was obtained. CSF from 11 normoxemic siblings was used for baseline values. HPLC was used to determine purine and pyrimidine metabolites in CSF, as measures of brain cell damage. Concentrations of purine and pyrimidine metabolites were significantly higher in hypoxemic lambs than in their siblings, whereas ECBA was lower in hypoxemic lambs. Significant negative linear relationships were found between purine and pyrimidine metabolite concentrations and, respectively, cerebral O(2) supply, cerebral O(2) consumption, and ECBA. We conclude that brain cell function is related to concentrations of purine and pyrimidine metabolites in the CSF. Reduction of ECBA indeed reflects the measure of brain damage due to hypoxemia in near-term newborn lambs.     

Brain cell function during hypoxemia in near-term lambs: a near-infrared spectroscopy study

BACKGROUND: Sufficient O2 supply to the brain is necessary for adequate cerebral energy metabolism, function and growth. OBJECTIVES: To elucidate the relation between changes in cerebral arterial O2 content and cerebral O2 supply and changes in the oxygenation state of cerebral hemoglobin, and to determine whether concentration changes in oxyhemoglobin (DeltacO2Hb), deoxyhemoglobin (DeltacHHb), and cerebral arterial oxygenation (DeltacHbD; the difference between DeltacO2Hb and DeltacHHb), and cerebral blood volume (DeltaCBV) can be used to assess the decline in brain cell function during hypoxemia in lambs born near term. METHODS: 17 preterm lambs were delivered at a mean gestational age of 133 days. Decreases in cerebral arterial oxygen content were induced by a stepwise reduction in inspired oxygen concentration. Mean values of all continuous variables were calculated over the last 180 s of each hypoxemic level. Cerebral arterial blood gases were analyzed at the end of each level to calculate cerebral arterial O2 content and cerebral O2 supply. RESULTS: Changes in cerebral arterial O2 content and cerebral O2 supply were positively linearly related with DeltacO2Hb and DeltacHbD, and negatively with DeltacHHb and the concentration changes in total hemoglobin. Electrocortical brain activity remained stable until the cO2Hb and cHbD decreased to >3.0 +/- 0.9 and >8.1 +/- 1.9 (mean +/- SD) micromol/100 g, respectively, and cHHb and CBV increased to >4.3 +/- 1.7 and 1.37 +/- 0.48 ml/100 g, respectively, as compared to baseline. CONCLUSIONS: Changes in cerebral arterial O2 content and cerebral O2 supply are adequately reflected by changes in the oxygenation state of cerebral hemoglobin. Concentration changes in DeltacO2Hb, DeltacHHb, DeltacHbD and DeltaCBV can be used to assess the decline in brain cell function during hypoxemia in lambs born near term.     

The effects of hypoxemia on myocardial blood flow during exercise

We evaluated the adequacy of regional and transmural blood flow during exercise and rapid pacing after 1 wk of hypoxemia. Seven mature mongrel dogs were made hypoxemic (mean O2 saturation = 72.4%) by anastomosis of left pulmonary artery to left atrial appendage. Catheters were placed in the left atrium, right atrium, pulmonary artery, and aorta. Atrial and ventricular pacing wires were placed. An aortic flow probe was placed to measure cardiac output. Ten nonshunted dogs, similarly instrumented, served as controls. Recovery time was approximately 1 wk. Cardiac output, mean aortic pressure, and oxygen saturation were measured at rest, with ventricular pacing, atrial pacing, and with treadmill exercise. Ventricular and atrial pace and exercise were at a heart rate of 200. Right ventricular free wall, left ventricular free wall, and septal blood flow were measured with radionuclide-labeled microspheres. Cardiac output, left atrial blood pressure, and aortic blood pressure were similar between the two groups of dogs in all testing states. Myocardial blood flow was significantly higher in the right and left ventricular free wall in the hypoxemic animals during resting and exercise testing states. Myocardial oxygen delivery was similar between the two groups of animals. Pacing resulted in an increase in myocardial blood flow in the control animals but not the hypoxemic animals.(ABSTRACT TRUNCATED AT 250 WORDS)     

The role of oxygen free radicals in postasphyxia cerebral hypoperfusion in newborn lambs

Previous work in a neonatal lamb model has demonstrated abnormalities in cerebral blood flow (CBF) and oxygen consumption (CMRO2) after asphyxia. Immediately after resuscitation, there was a marked increase in CBF and a significant decrease in CMRO2 compared to control. During the late period after asphyxia (30 min to 4 h), both CBF and CMRO2 were significantly depressed. The same postasphyxia model (n = 16) was used to examine the hypothesis that generation of oxygen free radicals during cerebral reperfusion may be involved in the genesis of late postasphyxia hypoperfusion and depressed CMRO2. Before asphyxia, the animals were pretreated with either inactivated (n = 8) or active (n = 8) polyethylene glycol superoxide dismutase, 5000 U/kg, and polyethylene glycol catalase, 100 000 U/kg. CBF (radioactive microspheres) and arterial and venous (superior sagittal sinus) blood gases and O2 contents were measured during control, and at 5 min, 1 h, 2 h, and 4 h postasphyxia (PA). In the active enzyme group, 5 min postasphyxia CBF was significantly increased compared to control: 211.5 +/- 28.0 versus 78.6 +/- 11.4 ml.100 g-1.min-1, +/- SEM, p less than 0.005. At 1 h (82.9 +/- 17.6), 2 h (62.3 +/- 5.5), and 4 h (78.9 +/- 12.2) PA, CBF did not differ significantly from control. More importantly, CMRO2 did not differ from control at any time PA. In the inactive enzyme group, both CBF and CMRO2 were depressed at 1, 2 and 4 h PA. These findings are consistent with a conclusion that damage by oxygen free radicals during postasphyxia cerebral reperfusion is important to the genesis of late PA blood flow and O2 metabolism abnormalities. To the extent that depressions in CBF and CMRO2 result in ongoing brain injury, agents that ameliorate these abnormalities may improve neurologic outcome.     

Cardiovascular changes during sustained lung inflations in premature newborn lambs

We studied the effect of sustained inspiratory inflations (SI) on the cardiovascular system by measuring mean central venous pressure (MCVP), mean arterial blood pressure (MABP) and heart rate (HR), before and during sustained lung inflations in premature lambs (128–133 days' gestation). SI consisted of four inflations of 5 s at a peak inspiratory pressure of 35 cmH₂O, with a mixture of 5 % carbon dioxide and 95% oxygen. Each inflation was followed by a positive end-expiratory pressure of 5 cmH₂O for 5 s. Percentage change from baseline was -3.88% for MABP and -2.55% for HR during the first inflation. The changes in MCVP fluctuated with each inflation (mean 9.61%;p < 0.01 versus baseline) and deflation (mean -3.87%; p < 0.05 versus baseline). These changes were dependent on the time after birth and the pressure used for SI. The observed cardiovascular changes produced by this procedure are considered clinically relevant when managing premature infants with a high risk of intraventricular haemorrhage.     

Influence of increased pulmonary vascular pressures on the closure of the ductus arteriosus in newborn lambs

Neonatal conditions associated with increased pulmonary artery pressure have an increased incidence of patent ductus arteriosus. We operated on 15 near term fetal lambs and placed mechanical occluders into or around both branch pulmonary arteries so that main pulmonary artery blood pressure could be controlled. The lambs were delivered and ventilated for 4 h. In seven lambs, the branch vessels were obstructed so that pulmonary artery pressure increased to equal aortic pressure; in eight lambs (control), the branch vessels were not obstructed. There were no significant differences between the two groups in circulating prostaglandin E2 or 6 keto F1 alpha concentrations, PaO2, pH, or PaCO2. Despite these similarities, ductus resistance in the lambs with elevated pulmonary pressure was significantly less than that in the control lambs. After the 4 h measurements, we studied the ductus in vitro. We have previously found that ductus arteriosus constriction produces ischemia of its muscle wall that limits its ability to dilate or constrict any further. Ductus from lambs with elevated pulmonary pressure had a significantly increased ability to respond to oxygen, prostaglandin E2, and indomethacin compared with ductus from control lambs; these findings are consistent with less ductus constriction in vivo. Thus, the high incidence of patent ductus arteriosus in neonates with elevated pulmonary vascular resistance may be due in part to the increased pulmonary vascular pressure, which opposes ductus constriction and preserves ductus responsiveness. Conversely, the normal drop in pulmonary pressure that occurs in full term infants may facilitate the closure of the ductus after delivery.     

Postprandial gastrointestinal blood flow and oxygen consumption: effects of hypoxemia in neonatal piglets

The effects of feeding on gastrointestinal (GI) perfusion and oxygen transport in hypoxemic neonates is unknown. We evaluated these effects in unanesthetized, spontaneously breathing newborn piglets by comparing three experimental groups: nine hypoxemic piglets (mean PaO2 26 torr) which were fed with formula, six hypoxemic piglets (mean PaO2 27 torr) which were not fed, and four normoxemic piglets (mean PaO2 79 torr) which were fed and served as controls. The control-fed group exhibited an increase in stomach and small intestinal mucosal-submucosal blood flow within 30 min following feeding which was significantly greater than that observed in the hypoxemic fed piglets. GI O2 delivery and O2 uptake rose significantly (p less than 0.05) following a meal secondary to increases in total GI blood flow. Oxygen extraction was unchanged postprandially in the control group. In the hypoxemic nonfed piglets, total and regional GI blood flow was unaltered during hypoxemia. Reductions in arterial O2 content led to significant decreases in GI O2 delivery. Gastrointestinal oxygen uptake remained stable with a compensatory increase in GI O2 extraction. In the hypoxemic-fed piglets, hypoxia significantly decreased stomach blood flow and led to unchanged blood flow in the remainder of the GI tract. Significant reductions in arterial O2 content and GI O2 delivery were observed, accompanied by significant increases in O2 extraction. Hypoxemic fed animals did not exhibit the expected increase in O2 uptake to meet postprandial metabolic demands. When the hypoxemic insult was terminated, fed piglets demonstrated significant total and regional GI hyperemia leading to increased GI O2 uptake when compared with hypoxemic nonfed piglets.(ABSTRACT TRUNCATED AT 250 WORDS)     

The afferent vagus and regulation of breathing in response to inhaled CO2 in awake newborn lambs.

Changes in steady state minute ventilation, tidal volume and frequency were determined in unanesthetized lambs before and after bilateral cervical vagotomy while breathing 3, 6, and 9% CO2 in 20% O2 balance N2. The slope of delta VE/delta PaCO2 fell from 0.068 to 0.033 while frequency response depended on intact vagi. Electrical stimulation of the cut proximal vagus (after bilateral vagotomy) restored CO2 responsiveness to control values. From these observations, it may be concluded that the afferent vagus is involved in the control of ventilation during hypercapnia and helps to modulate ventilatory frequency by inhibiting tidal volume.     

Splanchnic blood flow, oxygen delivery and oxygen consumption in hypotensive newborn piglets.

To investigate the relationship between splanchnic visceral oxygen supply and consumption, we altered O2 delivery by decreasing gastrointestinal blood flow during hypotension, and examined the effect on splanchnic oxygen consumption and extraction. We used 10 anesthetized newborn piglets, and measured blood flow using radioactive microspheres. Blood flow fell as perfusion pressure fell in all splanchnic organs, the correlation being most marked in the small intestine. Oxygen consumption was linearly related to blood pressure, and despite a rise in splanchnic oxygen extraction with low blood pressure, splanchnic oxygen consumption was highly dependent on oxygen delivery when oxygen delivery was below a critical value of 0.17 +/- 0.05 mmol/100 g/min. We conclude that the newborn piglet gut is incapable of maintaining a constant oxygen supply during the low-flow state produced by hypotension.     

Hepatic oxygen consumption, lactate uptake, and glucose production in neonatal lambs

Previous studies have evaluated neonatal hepatic metabolism in vitro, and neonatal hepatic oxygen consumption has been measured in vivo, but direct measurements of neonatal hepatic metabolism have not been reported. We studied seven neonatal lambs at age 7-10 days after placing catheters chronically in the hepatic vein, portal vein, descending aorta, left ventricle, and inferior vena cava. Hepatic blood flow was measured by the radioactive microsphere technique. Oxygen consumption and glucose and lactate fluxes were measured using the Fick principle. 14C-lactate was infused intravenously and lactate and glucose specific activities were measured and used to calculate hepatic gluconeogenesis from lactate. Neonatal hepatic blood flow was 254.5 +/- 50.3 ml/min/100 g (mean +/- SD) with 5.4 +/- 4.6% from the hepatic artery and 94.6 +/- 4.6% from the portal vein. Hepatic oxygen consumption was 7.2 +/- 2.4 ml/min/100 g and oxygen extraction was 44.9 +/- 15.4%. Oxygen extraction correlated inversely with oxygen delivery. In the seven lambs, there was net hepatic lactate uptake of 10.2 +/- 5.0 mg/min/100 g (1.13 +/- 0.56 mM) and hepatic glucose production of 30.8 +/- 11.3 mg/min/100 g (1.71 +/- 0.62 mM). In the five lambs in which hepatic gluconeogenesis was measured, 12.4 +/- 5 mg (1.37 +/- 0.56 mM) of lactate was converted to glucose per 100 g liver, accounting for 38.4% of the hepatic glucose production in these lambs. Blood flow and oxygen and substrate delivery to the neonatal liver are lower than those to the fetal liver but the neonatal liver extracts more oxygen and substrates and is able to produce glucose by gluconeogenesis from lactate.