Our aim was to determine whether the use of room air or 100% oxygen has different effects on the peripheral circulation during resuscitation from severe hypoxemia. Twenty-four piglets, 2-to 5-days old, were anesthetized with pentobarbital and randomized to control (n = 5, surgery only) or hypoxemia. Hypoxemia (FiO2 = 0.08) was continued until base excess reached - 20 mml/L. Resuscitation was then performed with 21% (n = 10) or 100% O2 (n = 9) for 25 min followed by 21% O2 in both groups. Regional blood flow was measured with radioactive microspheres. Both hypoxic groups showed marked hyperemia during resuscitation in cardiac and skeletal muscle, a moderate hyperemia in intestine and pancreas while kidneys, liver, spleen and skin showed no hyperemic response. There were no significant differences between the two treatment groups in blood flow to any organ. Arterial oxygen content was significantly higher in the 100% O2 group than in the 21% O2 at 5 and 20 min after onset of resuscitation (11.6 +/- 0.7 and 11.2 +/- 0.6 vs 8.6 +/- 0.3 and 8.7 +/- 0.3 ml/100 ml, p < 0.01). Oxygen delivery was, however, significantly higher in the 100% O2 group than in the 21% O2 group only to the intestine and pancreas at 5 min of resuscitation. We conclude that resuscitation with 21% or 100% oxygen produces similar changes in peripheral blood flow in this porcine model of neonatal hypoxemia.

To investigate the effect of hyperoxemia on the ocular circulation after a severe hypoxemic insult (8% O2 until base excess reached -20 mmol/l), we randomly reoxygenated newborn piglets with 100% (study group, n = 8) or 21% O2 (control group, n = 10). Retinal (RBF) and choroidal blood flow (ChBF) were measured with radioactive microspheres. The hypoxemic insult did not change RBF, while ChBF significantly decreased. However, a marked reduction in both retinal (RDO2) and choroidal oxygen delivery (ChDO2) was observed, probably resulting in hypoxia both in the inner and outer retina. At 5 and 20 min of reoxygenation a similar hyperemic response in the retina was seen in both groups. RDO2 also increased significantly and no significant differences between the 2 groups could be demonstrated. We found no indication of retinal vasoconstriction during hyperoxemia. We speculate that the vasodilating effect of the preceding hypoxemia overrules the vasoconstrictive effect of the retinal vessels normally found during hyperoxemia.

The isotope-labelled microsphere method was used to study blood flow autoregulation in the brainstem (BS), cerebellum (CBL), cerebrum (CBR) and choroid plexus (ChPl) in 21 newborn piglets exposed to hypoxemia and/or hypovolemia. One group of piglets (n = 7) was made hypoxemic by breathing 10% O2 for 10 min, a second group (n = 8) was studied during hypoxemia (10% O2, 10 min), followed by hypovolemia (bleeding 20% of estimated blood volume). A third group of piglets (n = 6) was made hypovolemic by bleeding 20%. Hypoxemia significantly impaired the autoregulatory capacity in CBL and CBR resulting in a pressure-passive flow pattern. Hypovolemia alone did not produce any significant cerebral vascular response in BS, CBL and CBR, not even when hypovolemia was preceded by hypoxemia, indicating a rapid restoration of the autoregulatory capacity of the cerebral vasculature after hypoxemia of moderate duration. The hypotension seen both during hypoxemia and hypovolemia was gradually compensated for and normalized within 60 min. However, animals exposed to both hypoxemia and hypovolemia were still hypotensive 60 min after the hypoxemic insult. Cardiac output (CO) was not affected by hypoxemia, but was consistently reduced in hypovolemia. We therefore speculate that in the newborn a reduced CO might be a more specific parameter for hypovolemia than a low blood pressure.

The effects of hypoxemia (HO, 8% O2) followed by resuscitation with 21% or 100% O2 on retinal (RBF) and choroidal blood flow (ChBF) were studied in 19 newborn piglets with the microsphere method. When base excess reached - 20 mmol/L or systolic blood pressure fell below 30 mmHg, the piglets were randomly resuscitated with either 21% O2 (n=10) or 100% O2, (n=9) for 25 min followed by 21% O2, in both groups. RBF and ChBF were measured at baseline (Bl), at the end of HO, and 5 min, 20 min and 60 min of reoxygenation. Flow values were (ml/min/100g, mea±SD) : HO significantly decreased ChBF, but not RBF. RBF significantly increased during 5 and 20 min of reoxygenation, while in ChBF this increase was only seen at 5 min of reoxgenation. Conclusion: We could not demonstrate any significant differences in RBF or ChBF between two groups of hypoxemic newborn piglets reoxygenated with 21% or 100% O2.

Intracranial hemorrhage in the premature infant is often associated with respiratory failure and need for mechanical ventilation. We therefore addressed the question of possible interactions with and pulmonary consequences of intraventricular hemorrhage. Newborn piglets were studied during intraventricular hemorrhage simulated by intraventricular blood infusion. Infusion volume amounted to 8% of estimated brain weight. Respiratory rate, minute ventilation, lung resistance and dynamic lung compliance, as well as arterial blood gases, arterial and intraventricular pressures were measured. The piglets were mechanically ventilated with a low basal rate of 20 breaths per minute throughout the study. All piglets experienced significant rise in intraventricular pressure and respiratory failure during the study. Respiratory failure was mainly a result of a reduction in respiratory frequency and minute ventilation until apnea. However, a rise in lung resistance was also noted while lung compliance did not change. We conclude that increased need for mechanical ventilation during intracranial hemorrhage is primarilty a consequence of hypoventilation. The increase seen in lung resistance could also suggest that intraventricular hemorrhage causes an element of bronchiolar constriction. Furthermore, these effects are not only a result of the increase in intraventricular pressure, but specific effects of blood components within the central nervous system must be considered.

The effect of hypoxemia and/or hypovolemia on ocular blood flow was studied in paralyzed and mechanically ventilated newborn piglets with the isotope-labelled microsphere method. Twenty-six piglets were studied in four different groups. One group of piglets (n = 6) was made hypoxemic by breathing 10% O2, a second group (n = 7) and a third group (n = 7) were studied during hypoxemia (10% O2), followed by hypovolemia (bleeding 20 and 30% of estimated blood volume, respectively). A fourth group of piglets (n = 6) was made hypovolemic by bleeding 20% of estimated blood volume. Hypoxemia resulted in a 2- to 3-fold increase in retinal blood flow (RBF), while hypovolemia did not change RBF, not even when preceded by a period of hypoxemia. In the case of choroidal blood flow (ChBF), the increase caused by hypoxemia was only 10-40%. Although ChBF decreased significantly during hypovolemia, no significant correlation between mean arterial blood pressure and ChBF was found. The results indicate that autoregulation is normally seen in RBF, but probably not in ChBF. However, during hypoxemia autoregulation was found neither in RBF nor in ChBF.

The effects of resuscitation with 21 or 100% O2 on cerebral blood flow (CBF) and somatosensory evoked potentials (SEPs) were studied in 19 newborn pigs anesthetized with pentobarbital sodium. They were ventilated with 8% O2 until base excess reached -20 mmol/l and then were randomly reoxygenated with 21% O2 (n = 10) or 100% O2 (n = 9) for 25 min followed by 21% O2. Mean duration of hypoxemia in the two groups was 57 +/- 6 (SE) and 59 +/- 6 min, respectively. CBF determined by radioactive microspheres was significantly increased in all areas in both groups after 5 and 20 min of reoxygenation. At 5 min of reoxygenation forebrain O2 uptake (CMRo2) had increased significantly compared with baseline values in the 21% O2 group (2.5 +/- 0.1 to 3.2 +/- 0.2 ml.100 g-1.min-1) but not in the 100% O2 group. There were, however, no significant differences between the two groups in CBF or CMRo2 at any time, and by 60 min of reoxygenation both had returned to baseline levels. SEPs were not significantly different in the two groups. We conclude that, as judged by CBF, CMRo2, and SEP, 21% O2 is not inferior to 100% O2 when hypoxemic newborn pigs are reoxygenated.

Using the isotope-labelled microsphere method, blood flow to the brain, the heart and the kidneys were studied in newborn piglets during nimodipine infusion. Twenty piglets were studied in two different groups. Group 1 (n = 8) was kept normoxic and given a continuous nimodipine infusion (15 micrograms/kg/min). Group 2 (n = 12) was made hypoxemic by breathing 10% O2 for 10 min followed by an identical nimodipine infusion as group 1. In spite of a significant systemic hypotension, nimodipine infusion alone significantly increased blood flow in the brain stem and right cardiac ventricle at 30-60 min of infusion, while blood flow to cerebellum, cerebrum and the left cardiac ventricle did not change. Blood flow to the kidneys decreased significantly. In posthypoxemic piglets nimodipine infusion gave almost similar flow patterns, however, the changes appeared at an earlier time. We conclude that in spite of a significant reduction in blood pressure, cerebral and cardiac blood flow is preserved both in normal and posthypoxemic animals even at high doses of nimodipine. However, because of the decreased blood flow to the kidneys further dose-response studies are needed before clinical use in asphyctic newborns.

The effects of hypoxemia (HO, 10% O2) and hypovolemia (HV, bleeding 20–30%) alone, or both insults combined, on retinal (RBF) and choroidal blood flow (ChBF) wete studied in 23 newborn piglets with the microsphere method. Surgery and experiments were performed under general anesthesia with 70% N2O. The piglets were ventilated paralyzed with pancuronium. RBF and ChBF were measured at baseline (Bl), during HO or at baseline 2 (Bl2), 20 min after HO (20′) or after HV, and 30 (30′) and 60 min (60′) after HO. Results were (ml/min/100g):RBF was significantly increased during HO, but was not affected by HV. ChBF was also increased during HO, but much less than RBF. HV significantly reduced ChBF. These different responses within the ocular vascular bed miqht have clinical significance.

The effect of hypoxemia (HO, 10% O2) with and without hypovolemia (HV, bleeding 20% 20 min (20') after HO) on cerebral blood flow (CBF) was studied in 14 newborn piglets with the microsphere method. Surgery and experiments were performed under general anesthesia with 70% N2O. The piglets were ventilated paralyzed with pancuronium. CBF was measured in brainstem (BR), cerebellum (CE) and cerebrum (CR) at baseline (BS), during HO and after HV, and 30 (30') and 60 min (60') after HO. Results were (ml/100g/min, mean ± SD.): HO significantly increases CBF. HV following HO reduces blood flow significantly in both CE and CR compared to BS. BR seems more stable to this insult.

This study includes 57 children born at term with asphyxia and admitted to Children's Department, Rikshospitalet, during the period 1981-85. The mortality in this study was 14% which proves that asphyxia represents a serious illness in newborn infants. The results of this investigation confirm that Apgar score is not a very precise parameter and offers limited information when estimating prognosis after birth. 17% of the newborn infants suffered from neonatal seizures during their first day in the neonatal period, and this symptom appears to indicate a high risk of subsequent mortality and morbidity. Nearly 44% of the newborns needed mechanical ventilation.

ABSTRACTOdden, J.‐P., Stiris, T., Hansen, T. W. R. and Bratlid, D. (Neonatal Research Laboratory, Department of Paediatric Research, Institute for Surgical Research and Department of Paediatrics, Rikshospitalet, University of Oslo, Oslo, Norway). Cerebral blood flow during experimental hypoxaemia and ischaemia in the newborn piglet. Acta Paediatr Scand Suppl 360: 13, 1989.The effect of selective hypoxaemia or ischaemia on cerebral blood flow was studied in 14 newborn piglets with the microsphere method. Surgery and experiments were performed under general anesthesia with 70% nitrous oxide. The spontaneously breathing piglet was then exposed to either low (zero) oxygen in the inspired air (hypoxaemia), or a graded tourniquet (3–5 kg string weight) of the neck above the level of the tracheostomy (ischaemia). Cerebral blood flow was measured at baseline, during the hypoxaemic/ischaemic insult, and 30 and 60 min thereafter. Brainstem blood flow was remarkably stable during both ischaemia and hypoxaemia. The reduction in blood flow to the cerebrum and to the cerebellum was greater during ischaemia than during hypoxaemia. Reactive hyperaemia followed hypoxaemia but was not obvious after selective ischaemia. Ischaemia and hypoxaemia thus seem to have different effects on cerebral blood flow.

ABSTRACT: The response of ocular and cerebral blood flow to different arterial Pco2 levels was studied in ventilated paralyzed newborn piglets with the radionuclidelabeled microsphere method. The retina and the choroid have different blood flow responses to variations in arterial Pco2 levels. Retinal blood flow (ml/g/min) was increased during hypercarbia, from 0.26 ± 0.03 at baseline to 0.51 ± 0.07 (Paco2 8.7 ± 0.2 kPa) and 0.62 ± 0.07 (Paco2 11.0 ± 0.2 kPa). However, no significant change was found in choroidal blood flow during hypercarbia. Cerebral blood flow was more responsive to Paco2 than retinal blood flow, increasing from 0.71 ± 0.03 at baseline to 2.25 ± 0.25 (Paco2 8.7 ± 0.2) and 1.77 ± 0.13 (Paco2 11.0 ± 0.2). Hypocarbia did not influence either retinal or choroidal blood flow.

The effects of hyperoxia on the entry of bilirubin and albumin into the brain were studied in five to six-week-old male Sprague-Dawley rats. Bilirubin was infused at 20 mg/kg/hour for three hours through a carotid catheter, resulting in serum bilirubin levels of 200-220 microM at 180 minutes. Group 1 (n = 8) was normoxic at all times. Group 2 (n = 8) was given oxygen (FiO2 = 0.75 -0.80) for the last hour of the three-hour bilirubin infusion. Group 3 (n = 10) was given oxygen (FiO2 = 0.75 -0.80) for 24-27 hours prior to, as well as during the bilirubin infusion. No significant differences were found in brain bilirubin (as measured by chloroform extraction) or brain albumin (as measured by 125I-albumin uptake) between the groups. Under these experimental conditions, hyperoxia does not increase bilirubin deposition in rat brain nor does it cause opening of the blood-brain barrier as measured by albumin entry into the brain.

The entry of bilirubin into brain is facilitated by displacing agents, and by factors affecting the permeability of the blood-brain barrier. It has been suggested that hyperoxia may increase bilirubin entry into brain. We have investigated the effects of short term (1 hr) and long term (27-30 hrs) hyperoxia on the entry of bilirubin into rat brain. Bilirubin 20 mg/kg/hr was infused for 3 hrs into awake, 5-6 weeks old male Sprague-Dawley rats. Prior to the infusion each rat was given 10-20 uCi 125I-human serum albumin. In group 1 (n=8) the rats breathed room air at all times. In group 2 (n=8) the rats were exposed to 80% oxygen during the last 60 minutes of the bilirubin infusion. In group 3 (n=10) the rats were kept in 70-80% oxygen for 24-27 hrs prior to, as well as during the bilirubin infusion. After 3 hrs the rats were sacrificed and the brain perfused in situ with icecold saline 20 ml/min for 3 minutes. Brain albumin was estimated by counting the activity in one half brain and in a serum sample. Brain bilirubin was determined by chloroform extraction from the other half. Results: None of the differences are significant at the 5% level. We therefore conclude that hyperoxia does not increase bilirubin deposition in rat brain.