Changes in cerebral, renal and mesenteric blood flow velocity during continuous and bolus infusion of indomethacin.

UNLABELLED: Vasoconstriction induced by bolus injection of indomethacin reduces organ perfusion and has been related to the well-known side effects of indomethacin given for closure of the patent ductus arteriosus (PDA). The aim of the study was to compare the changes in cerebral, renal and mesenteric blood flow velocities after continuous infusion versus bolus injection of indomethacin for closure of the PDA. Thirty-two preterm infants (range 26-35 wk gestational age) with PDA were randomly assigned to receive the same amount of indomethacin either as three bolus injections (n = 14) or as a continuous infusion (n = 18) over 36 h. Blood flow velocities were measured in the internal carotid, right renal and superior mesenteric arteries at baseline and serially at 10, 30, 60 and 120 min and 12, 24, 36 and 48 h after the start of indomethacin treatment. There were no differences in blood flow velocities between both groups at baseline. During continuous infusion of indomethacin there was no significant change in the cerebral, renal and mesenteric blood flow velocities, whereas the flow velocities in the infants receiving bolus injections decreased significantly during the first 2 h after indomethacin administration in all arteries measured. There was a transient, but significant reduction in urine output after bolus injection of indomethacin. CONCLUSION: In contrast to bolus injections, decrease of organ blood flow and impairment of urine output do not accompany continuous infusion of indomethacin over 36 h.

Recirculation in double lumen catheter veno-venous extracorporeal membrane oxygenation measured by an ultrasound dilution technique.

Recirculation is a limiting factor for oxygen delivery in double lumen catheter veno-venous extracorporeal membrane oxygenation (DLVV-ECMO). This study compares three different methods for the determination of the recirculation fraction during double lumen catheter veno-venous ECMO at ECMO flow rates of 150, 125, 100, 75, and 50 ml/kg.min in nine lambs: (1) an ultrasound dilution method, in which the change in ultrasound velocity in blood after injection of a saline bolus as a marker is used for determination of recirculation; (2) an SvO2 method using real mixed venous blood oxygen saturation, the gold standard, for determination of recirculation fraction; and (3) the CVL method, in which oxygen saturation of a blood sample of the inferior vena cava is considered to represent mixed venous oxygen saturation. In all methods, the recirculation fraction increased with increasing ECMO flow rate. The correlation coefficient between the ultrasound dilution method and the SvO2 method was 0.68 (p < 0.01); mean difference was -2.4% (p = 0.6). Correlation coefficient between the ultrasound dilution method and the CVL method was 0.48 (p < 0.01); mean difference was -18.1% (p < 0.01). The correlation coefficient between the SvO2 method and the CVL method was 0.51 (p < 0.01); mean difference was -15.7% (p < 0.01). The ultrasound dilution method is a useful method for measurement of the recirculation fraction in DLVV-ECMO and is easier to use than the other methods.

Changes in electrocortical brain activity during exchange transfusions in newborn infants.

Electrocortical brain activity (ECBA) was recorded continuously with a cerebral function monitor during 17 exchange transfusions in 13 infants (mean gestational age 36.3 +/- 1.9 weeks, birth weight 2,800 +/- 635 g). The minimum and maximum amplitudes, and bandwidth of the ECBA signal were determined at the end of each withdrawal and infusion period. Mean arterial blood pressure (MABP), and the minimum and maximum amplitudes decreased during the withdrawal period and increased during the infusion period. The minimum and maximum amplitude changes were very small (< 6% of baseline) and appeared to be primarily associated with MABP changes. We conclude that exchange transfusions do cause minor changes in ECBA, which are probably not clinically relevant.

Cardiac output and ductal reopening during phototherapy in preterm infants.

Left ventricular output (LVO), left pulmonary artery blood flow (LPA) and patency of the ductus arteriosus (PDA) were studied with 2D/pulsed Doppler ultrasound before, during and after phototherapy treatment in 27 preterm infants (gestational age < or =32 wk), who were exposed for a minimum of 12 h to phototherapy for non-haemolytic hyperbilirubinemia. In 14 infants (52%) the ductus arteriosus reopened during phototherapy, but ductal patency was not of haemodynamic importance. LVO initially decreased in preterm infants in whom the ductus did not reopen. From 12 h until discontinuation of phototherapy, LVO and LPA were higher than before phototherapy in all infants. After withdrawal of phototherapy, LVO and LPA returned to pre-phototherapy values.

Electrocortical brain activity during hypoxia and hypotension in anesthetized newborn lambs.

Blood gas and blood pressure disturbances do influence cerebral blood flow in newborns. To what extent cerebral blood flow changes affect electrocortical brain activity remains uncertain. We studied the effect of severe hypoxia and hemorrhagic hypotension on carotid artery blood flow and electrocortical brain activity in newborn anesthetized lambs. During hypoxia carotid artery blood flow increased significantly, whereas electrocortical brain activity remained unchanged. The hemorrhagic hypotension study showed that the lower limit of the autoregulatory ability of the cerebral vascular bed was 60 mmHg. Electrocortical brain activity however remained stable until mean aortic pressure had dropped below 30 mmHg, carotid artery blood flow below 10.6 ml/kg/min, and cerebral oxygen delivery below 1.4 ml/kg/min.

Doppler sonographic study of the effect of indomethacin on cardiac and pulmonary hemodynamics of the preterm infant.

OBJECTIVE: Indomethacin (INDO) causes an increase in systemic vascular resistance and decrease in perfusion of important organ systems in preterm infants treated for patent ductus arteriosus (PDA). Information on the effect of INDO on cardiac and pulmonary hemodynamics of these babies is scarce. METHODS: The left ventricular output (LVO), resistance in the ascending aorta (R(Ao)), determined mean cerebral blood velocity (cerebral-mv), ductal-peak and mean blood velocity (ductal-pv and -mv) and pulmonary artery peak and mean blood velocity (pulmonary pv and -mv) were measured, before, and up to 12 h after 0.1 mg/kg of INDO in 20 preterm infants with PDA using Doppler echocardiography. RESULTS: LVO was abnormally high (mean+/-S.E.M.: 354+/-50 ml/min/kg) before INDO treatment, and an important left-to-right shunt through the ductus was detectable in all infants. At 1 h after INDO treatment, R(Ao) had significantly increased with a significant decrease in LVO and cerebral-mv. Ductal patency and pulmonary vascular resistance seemed not to be affected at this early stage, as indicated by unchanged ductal and pulmonary arterial blood velocities. At 4 h post-INDO, ductal-pv and -mv, and to a lesser extent pulmonary-pv and -mv, were transiently lower as compared to pre-INDO, 1 and 12 h post-INDO values. This coincided with a transient absence of clinical signs of PDA at 4 h post-INDO in a substantial number of infants. R(Ao) steadily decreased and LVO steadily increased, whereas cerebral-mv normalized from 4 h post-INDO onward. CONCLUSIONS: no important action of INDO was detected on pulmonary arterial blood velocity or pulmonary function.

[Clinical thinking and decision making in practice: a full-term neonate with misunderstood respiratory insufficiency]. / Klinisch denken en beslissen in de praktijk: een voldragen pasgeborene met onbegrepen respiratoire insufficiëntie.

A fullterm newborn boy developed severe respiratory insufficiency, multiple air leaks and severe pulmonary hypertension, leading to his death on the third day of life. Family history revealed that a sister of the patient had died earlier after a similar course with respiratory problems. The most common causes of respiratory insufficiency could be subsequently excluded. After extensive postmortem investigation alveolar proteinosis was found in the lung tissue. DNA investigation was then performed in the parents, and both appeared to be heterozygotic for the 121ins2 mutation. This finding suggests both children in this family to have been homozygotic for the 121ins2 mutation resulting in a lack of synthesis of surfactant protein B (SP-B). Homozygotic SP-B deficiency in the newborn is a fatal disease with no curative perspectives, except for lung transplantation and gene therapy.

[Results of extracorporeal membrane oxygenation in 100 newborns with cardiorespiratory insufficiency]. / Resultaten van extracorporele membraanoxygenatie bij 100 pasgeborenen met cardiorespiratoire insufficiëntie.

OBJECTIVE: To describe the results of treatment with extracorporeal membrane oxygenation (ECMO) in newborns with severe cardiorespiratory insufficiency. DESIGN: Prospective, descriptive. METHODS: For all 100 newborns treated with ECMO in 1989-1997 in the Academic Hospital Nijmegen, department of Neonatology, the Netherlands, indications for treatment, complications during treatment and mortality within 6 weeks after cessation of ECMO were registered. RESULTS: The 100 children comprised 66 boys and 34 girls, with a mean age of 2 days (range: 1-15). Indications for ECMO treatment were: meconium aspiration syndrome: 39 with 37 survivors (95%), congenital diaphragmatic hernia: 31 with 23 survivors (74%), sepsis or pneumonia: 20 with 14 survivors (70%) and 'others' among which persistent pulmonary hypertension of the newborn: 10 with 8 survivors (80%). Eighteen children died (18%). Causes of death were rebound pulmonary hypertension (9 times), intracranial haemorrhage (4), multi-organ failure (3) and pulmonary problems (2). The most important complications during treatment were bleeding problems (29), clotting problems (20) and infections (11).

Haemodynamic consequences of phototherapy in term infants.

UNLABELLED: The effect of blue-light phototherapy on cardiac output and brain and kidney perfusion was studied in 12 term infants with pulsed Doppler ultrasound. Mean (+/-SD) gestational age and birth weight were 39.0 (+/-1.6) weeks and 3438 (+/-533) g respectively. Mean (+/-SD) age of the infants at which phototherapy was initiated was 3.5 (+/-0.8) days. Left ventricular output (LVO), mean left pulmonary artery blood flow (LPA), mean blood flow velocities of the internal carotid (CBFV) and renal (RBFV) arteries were studied in all infants prior to the onset of phototherapy, 30 min, 2 h, and 12 h after initiation of phototherapy, and before and 12-24 h after discontinuation of phototherapy. LVO decreased immediately after the onset of phototherapy. However, after 12 h, LVO returned to pre-phototherapy values. LPA increased significantly after 12 h of exposure. LPA returned to pre-phototherapy values after discontinuation of phototherapy. CBFV increased, whereas RBFV decreased significantly after 2 h of exposure. After discontinuation of phototherapy CBFV as well as RBFV values returned to pre-phototherapy values. CONCLUSION: Phototherapy does affect cardiac output and organ blood flow velocity in term infants. After termination of phototherapy the effect of phototherapy disappears.

Effect of exchange transfusion on brain perfusion and electrocortical brain activity in newborn lambs.

Changes in brain perfusion (using ultrasonic-determined changes in carotid artery blood flow: Qcar) and electrocortical brain activity (ECBA, obtained by a Lectromed cerebral function monitor) were studied during exchange transfusion using the push-pull method in the newborn lamb. Changes in mean arterial blood pressure (MABP), Qcar, heart rate (HR), and ECBA were observed during all exchange transfusions: MABP, Qcar, and ECBA decreased during the withdrawal period and increased during the infusion period, whereas HR showed the opposite phenomenon. Changes in ECBA appeared to be primarily associated with changes in brain perfusion (p < 0.05). These changes in brain perfusion were, however, caused by changes in MABP (p < 0.0001). We concluded that exchange transfusions caused moderate changes in brain perfusion, however changes in ECBA appeared to be very small, and have probably no clinical importance.

The effect of phototherapy on cerebral blood flow velocity in preterm infants.

Cerebral blood flow velocity was studied with two-dimensional/pulsed Doppler ultrasound before, during and after discontinuation of phototherapy in 22 preterm infants (gestational age < or =32 weeks), who were treated for a minimum of 12h with blue-light phototherapy for non-haemolytic hyperbilirubinaemia. Before the cerebral blood flow velocity measurements, patency of the ductus arteriosus was diagnosed by Doppler echocardiography. All infants had normal brain ultrasound scans. Mean cerebral blood flow velocity increased significantly after initiation of phototherapy in all infants. Only in "healthy" (non-ventilated) infants did cerebral blood flow velocity return to pre-phototherapy values (baseline) after discontinuation of phototherapy, whereas in "unhealthy" (ventilated) infants cerebral blood flow velocity did not return to baseline. In 10 infants the ductus arteriosus reopened during phototherapy. In those infants, mean cerebral blood flow velocity returned to pre-phototherapy values after 2 h of phototherapy prior to its discontinuation.

The effect of phototherapy on renal blood flow velocity in preterm infants.

Mean renal blood flow velocity (RBFV) was studied with two-dimensional/ pulsed Doppler ultrasound and relative renal vascular resistance (RVR) was calculated before, during, and after phototherapy treatment in 30 preterm infants (gestational age < or = 32 weeks) who were treated for a minimum of 12 h with phototherapy for nonhemolytic hyperbilirubinemia. RBFV decreased, whereas RVR increased significantly after the initiation of phototherapy. In 'healthy' (nonventilated) infants RBFV and RVR returned to baseline values after discontinuation of phototherapy. Whereas in 'unhealthy' (ventilated) infants, RBFV and RVR did not return to baseline values after discontinuation of phototherapy. In 16 infants (> 50% of the cases) the ductus arteriosus reopened during phototherapy.

Effect of allopurinol on postasphyxial free radical formation, cerebral hemodynamics, and electrical brain activity.

OBJECTIVE: Free radical-induced postasphyxial reperfusion injury has been recognized as an important cause of brain tissue damage. We investigated the effect of high-dose allopurinol (ALLO; 40 mg/kg), a xanthine-oxidase inhibitor and free radical scavenger, on free radical status in severely asphyxiated newborns and on postasphyxial cerebral perfusion and electrical brain activity. METHODS: Free radical status was assessed by serial plasma determination of nonprotein-bound iron (microM), antioxidative capacity, and malondialdehyde (MDA; microM). Cerebral perfusion was investigated by monitoring changes in cerebral blood volume (delta CBV; mL/100 g brain tissue) with near infrared spectroscopy; electrocortical brain activity (ECBA) was assessed in microvolts by cerebral function monitor. Eleven infants received 40 mg/kg ALLO intravenously, and 11 infants served as controls (CONT). Plasma nonprotein-bound iron, antioxidative capacity, and MDA were measured before 4 hours, between 16 and 20 hours, and at the second and third days of age. Changes in CBV and ECBA were monitored between 4 and 8, 16 and 20, 58 and 62, and 104 and 110 hours of age. RESULTS: Six CONT and two ALLO infants died after neurologic deterioration. No toxic side effects of ALLO were detected. Nonprotein-bound iron (mean +/- SEM) in the CONT group showed an initial rise (18.7 +/- 4.6 microM to 21.3 +/- 3.4 microM) but dropped to 7.4 +/- 3.5 microM at day 3; in the ALLO group it dropped from 15.5 +/- 4.6 microM to 0 microM at day 3. Uric acid was significantly lower in ALLO-treated infants from 16 hours of life on. MDA remained stable in the ALLO group, but increased in the CONT group at 8 to 16 hours versus < 4 hours (mean +/- SEM; 0.83 +/- 0.31 microM vs 0.50 +/- 0.14 microM). During 4 to 8 hours, delta CBV-CONT showed a larger drop than delta CBV-ALLO from baseline. During the subsequent registrations CBV remained stable in both groups. ECBA-CONT decreased, but ECBA-ALLO remained stable during 4 to 8 hours of age. Neonates who died had the largest drops in CBV and ECBA. CONCLUSION: This study suggests a beneficial effect of ALLO treatment on free radical formation, CBV, and electrical brain activity, without toxic side effects.

Oxidative stress during post-hypoxic-ischemic reperfusion in the newborn lamb: the effect of nitric oxide synthesis inhibition.

Post-hypoxic-ischemic (HI) reperfusion induces endothelium and neurons to produce excessive amounts of nitric oxide and superoxide, leading to peroxynitrite formation, release of protein-bound metal ions (i.e. iron), and cytotoxic oxidants. We produced severe HI in 18 newborn lambs and serially determined plasma prooxidants (non-protein-bound iron), lipid peroxidation (malondialdehyde), and antioxidative capacity [ratio of ascorbic acid/dehydroascorbic acid (AA/DHA), alpha-tocopherol, sulfhydryl groups, allantoin/uric acid ratio, and vitamin A] in blood effluent from the brain before and at 15, 60, 120, and 180 min after HI. The lambs were divided in three groups: six received a placebo (CONT), six received low dose (10 mg/kg/i.v.) N omega-nitro-L-arginine (NLA-10) to block nitric oxide production, and six received high dose NLA (40 mg/kg/i.v.; NLA-40), immediately after completion of HI. Non-protein-bound iron increased in all groups after HI but was significantly lower in both NLA groups at 180 min post-HI (p < 0.05), the AA/DHA ratio showed a consistent decrease in CONT (at 60 min post-HI, p < 0.05), but remained stable in NLA lambs. alpha-Tocopherol decreased steadily in the CONT, but not in the NLA lambs [180 post-H: 1.9 +/- 0.9 versus 4.2 +/- 0.7 microM (NLA-40), p < 0.05). Malondialdehyde was significantly higher in CONT lambs 120 min post-H compared with NLA groups [0.61 +/- 017 versus 0.44 +/- 0.05 microM (NLA-40), p < 0.05]. Vitamin A and sulfhydryl groups did not differ among groups. We conclude that post-H inhibition of nitric oxide synthesis diminishes non-protein-bound iron increment and preserves antioxidant capacity.

Effect of post-hypoxic-ischemic inhibition of nitric oxide synthesis on cerebral blood flow, metabolism and electrocortical brain activity in newborn lambs.

Since an excessive production of nitric oxide upon reperfusion/reoxygenation may play an important role in post-hypoxic-ischemic (HI) brain injury, we investigated whether immediate post-HI blockade of nitric oxide synthesis by N-omega-nitro-L-arginine (NLA) may reduce this injury. In 18 newborn lambs, subjected to severe HI, changes from pre-HI values were measured for carotid blood flow (Qcar [ml/min]) as a measure of changes in brain blood flow, (relative) cerebral metabolic rate of oxygen (CMRO2), and electrocortical brain activity (ECBA) at 15, 60, 120 and 180 min after HI. Upon completion of HI, at the onset of reperfusion and reoxygenation, 6 lambs received a placebo (control group), 6 low-dose NLA (10 mg/kg i.v., NLA-10 group), and 6 high-dose NLA (40 mg/kg i.v., NLA-40 group). Histological damage to cerebellar Purkinje cells was assessed after termination of the experiment. Only the control group showed a distinct initial post-HI cerebral hyperperfusion. From 60 min after HI onward Qcar was decreased to about 75% of pre-HI Qcar in all 3 groups, although none of these changes in Qcar reached statistical significance. Despite the decreased Qcar in all 3 groups, only the control group showed a significantly decreased CMRO2. ECBA and its bandwidth decreased in all groups, but only recovered in the NLA-10 group 180 min after HI. The brain to body mass ratio (%) and percentage necrotic Purkinje cells were, respectively: 15.3 +/- 0.8 and 56 +/- 10 (control group); 12.5 +/- 1.2 and 36 +/- 9 (NLA-10 group), and 11.3 +/- 1.0 (p < 0.05 vs. the control group) and 35 +/- 14 (NLA-40 group). Since post-HI reperfusion injury of the brain has been characterized by a decreased CMRO2 and electrical brain activity, we conclude that preservation of CMRO2 in both NLA groups, but a recovery of ECBA and its bandwidth only in the NLA-10 group, suggests that NLA, and especially low-dose NLA, may reduce post-HI brain injury.

[Hyperbilirubinemia in full-term neonates: sequelae for long-term development better than expected. Ad-hoc Commission Hyperbilirubinemia and Phototherapy of the Section Neonatology of the Netherlands Society for Pediatrics]. / Hyperbilirubinemie bij voldragen pasgeborenen: gevolgen voor de ontwikkeling op lange termijn vallen mee. Ad-hoccommissie Hyperbilirubinemie en Fototherapie van de sectie Neonatologie van de Nederlandse Vereniging voor Kindergeneeskunde.

OBJECTIVE: Critical evaluation of guidelines for treatment of hyperbilirubinaemia in healthy full-term newborns, based on literature data concerning effects of hyperbilirubinaemia on later development. DESIGN: Structured literature survey. SETTING: Groningen, the Netherlands. METHODS: By electronic and hand searching of literature according to published guidelines data were collected on the relation between the peak total serum bilirubin concentration (TSB) in the first week of life and later development. RESULTS: One large study, the Collaborative Perinatal Project (CPP), showed statistically significant negative associations of TSB in the first week of life with Bayley development score at age 8 months, intelligence quotient (IQ) at age 4 years, and unspecified neurological abnormalities at age 7-8 years. In other studies, with considerable less power than the CPP, no such findings were made. In the original analyses of the CPP no correction was made for confounders and effect modifiers; after correction for such variables, a relation between TSB in the first week of life and later development was no longer found. At the age of 6 years, no statistically significant differences in IQ, hearing, and neurological abnormalities were found between children who, as newborns, had or had not been treated with phototherapy because of hyperbilirubinaemia. CONCLUSION: Treatment for jaundice in healthy full-term newborns is only indicated at considerably higher serum bilirubin levels than those recommended previously.

[Hyperbilirubinemia in healthy full-term neonates: guidelines for diagnosis and treatment. Ad-hoc Commission Hyperbilirubinemia and Phototherapy of the Section Neonatology of the Netherlands Society for Pediatrics]. / Hyperbilirubinemie bij gezonde voldragen pasgeborenen: richtlijnen voor diagnostiek en behandeling. Ad-hoccommissie Hyperbilirubinemie en Fototherapie van de sectie Neonatologie van de Nederlandse Vereniging voor Kindergeneeskunde.

In healthy full-term neonates without haemolytic disease, hyperbilirubinaemia is not associated with neurological, auditory or cognitive disorders later in life. Therefore, the new threshold levels of hyperbilirubinaemia at which further diagnosis and treatment are indicated, are higher than the former ones.

Nonprotein-bound iron in postasphyxial reperfusion injury of the newborn.

OBJECTIVE: To investigate if the availability of nonprotein-bound iron after birth asphyxia is related to the severity of the postasphyxial injury and neurodevelopmental outcome. METHODS: Nonprotein-bound iron (bleomycin assay) and thiobarbituric-acid-reactive species, an index of oxidative lipid damage, were measured in plasma of 50 newborn infants (gestational age > 34 weeks) between 0 to 8 hours, 8 to 16 hours, and 16 to 24 hours after birth. Three groups were compared: healthy infants (n = 20), moderately asphyxiated infants (n = 15), who were neurologically normal during the first 24 hours after birth and severely asphyxiated infants (n = 15), who developed abnormal neurological signs in the first 24 hours after birth. RESULTS: In the severely asphyxiated infants, liver enzymes, creatinine, urea, and uric acid concentrations were significantly elevated. Eleven severely asphyxiated infants were brain-damaged, 9 of them died during the neonatal period. Nonprotein-bound iron was detectable in 30% of the control, 60% of the moderately asphyxiated, and 80% of the severely asphyxiated infants. During the whole study period nonprotein-bound iron concentration was significantly elevated in severely asphyxiated infants as compared with controls. Three of the four severely asphyxiated infants who had a normal outcome at 1 year of age, had no detectable nonprotein-bound iron during the study period. Stepwise logistic regression analysis with neurodevelopmental outcome at 1 year of age (normal versus adverse/death) as dependent variable and all the measured parameters for organ damage as independent variables revealed that the nonprotein-bound iron concentration at 0 to 8 hours after birth was the most significant variable and at the same time the only variable that entered the model, in relation to neurodevelopmental outcome. Thiobarbituric-acid-reactive species tended to be higher in severely asphyxiated infants, suggesting oxidative lipid damage. CONCLUSION: Nonprotein-bound iron may play an important role in oxidative damage-mediated postasphyxial brain injury and subsequent neurodevelopmental outcome.

Changes in cerebral hemodynamics and oxygenation during hypothermic cardiopulmonary bypass in neonates and infants.

Delay in development after open-heart surgery in infants has frequently been reported. Inadequate brain perfusion and oxygenation during deep hypothermic cardiopulmonary bypass (CPB) may play an important role. We investigated the effect of CPB on cerebral perfusion and oxygenation in 12 neonates and infants (age 0-11 months) undergoing open-heart surgery. Changes in cerebral blood volume (delta CBV; in ml/100 g brain tissue) and oxidation level of the intracerebral mitochondrial enzyme cytochrome aa3 (delta Cytaa3; in mumol/l) were measured with near infrared spectroscopy. Nasopharyngeal temperature (Tnas) for assessment of changes in brain temperature, and mean arterial blood pressure (MAP) were monitored continuously. CBV lowered during cooling and increased during rewarming. These changes were only related with changes in Tnas (p < 0.001; 0.07 ml.100 g-1/ degrees C). No relation was found with changes in MAP or pump flow rate of the heart-lung machine. During steady-state hypothermic CPB, changes in CBV were only related to changes in MAP (p < 0.001). The individual regression lines between delta CBV and MAP became steeper at lower absolute Tnas. Cytaa3 showed an increase shortly after the initiation of CPB in 9 patients, with a sustained decrease to baseline values in 8 patients towards the end of the CPB period. Two patients who had a circulatory arrest during CPB had a sharp decrease in delta cytaa3 after cessation of the heart-lung pump and showed no complete recovery of delta Cytaa3 to baseline at the end of the CPB period. We conclude that changes in CBV during CPB are related to changes in Tnas. During deep hypothermic steady-state CPB, changes in CBV and MAP were related to each other, suggesting lack of cerebral autoregulation. The large decrease in Cytaa3 in 2 patients with circulatory arrest suggests that this procedure compromises energy metabolism of the brain cell.

Inhalation of nitric oxide: effect on cerebral hemodynamics and activity, and antioxidant status in the newborn lamb.

Ventilation with nitric oxide (NO) is increasingly being used to treat pulmonary hypertension in the newborn. In the brain, NO has vasoactive properties and is involved in neurotransmission. However, the effect of inhaled NO on the cerebral blood flow (CBF) and on the cerebral activity is not known. Furthermore, there is little information on the influence of this free radical gas on the redox status in pulmonary vessels. We therefore investigated the effect of inhaled NO (2-60 ppm) on CBF, cerebral activity and redox status in blood effluent from the pulmonary circulation in 6 ventilated newborn lambs before and during group B streptococci (GBS)-induced pulmonary hypertension. Blood pressure in the pulmonary artery (P(ap)) and aorta (Pao), carotid artery blood flow (Qcar) to assess changes in CBF, and electrocortical activity were measured. Blood gases, indices of free radical status and methemoglobin were determined in blood samples obtained from the left ventricle. Inhalation of NO, before and during GBS-induced pulmonary hypertension, decreased P(ap) and PCO2 and increased PO2. Multiple linear regression revealed that Qcar was positively related to PCO2, but not to inhaled NO or PO2 before or during GBS conditions. Electrocortical activity and indices of antioxidative capacity and lipid peroxidation did not change significantly. Methemoglobin was not detected. In conclusion, inhalation of NO (up to 60 ppm) lowered P(ap) without directly affecting CBF, electrocortical activity, and redox status in the pulmonary vessels. CBF, however, can indirectly be influenced by NO-mediated changes in PCO2.