Different subsets of circulating angiogenic cells do not predict bronchopulmonary dysplasia or other diseases of prematurity in preterm infants.

Bronchopulmonary dysplasia (BPD) is a chronic lung disease occurring in very and extremely preterm infants undergoing mechanical ventilation. Given the altered lung vascular growth characterizing BPD, circulating angiogenic cells could be useful biomarkers to predict the risk. The objective of the study was to determine whether the percentages of circulating angiogenic cells (CD34+VEGFR-2+, CD34+CD133+VEGFR-2+, and CD45-CD34+CD133+VEGFR-2+ cells), assessed in the peripheral blood at birth by flow cytometry, could be used as markers for the risk of BPD. In one-hundred and forty-two preterm neonates (gestational age less than 32 weeks and/or birth weight less than 1500 g) admitted to our tertiary care Neonatal Intensive Care Unit between 2006 and 2009, we evaluated the percentages of circulating angiogenic cells at birth, at 7 days, and, in a subset of infants (n=40), at 28 days of life. The main outcome was the correlation between cell counts at birth and the subsequent risk of developing BPD. In our study, all the three cell populations failed to predict the development of BPD or other diseases of prematurity. We suggest that these cells cannot be used as biomarkers in preterm infants, and that research is needed to find other early predictors of BPD.

Adjunctive effect of chlorhexidine antiseptics in mechanical periodontal treatment: first results of a preliminary case series.

OBJECTIVES: The aim of the present case series was to evaluate the clinical and microbiological effects of a single session of mechanical and manual scaling and root planing (SRP) combined with the use of two different chlorhexidine formulations in the treatment for generalized chronic periodontitis. METHODS: Ten patients affected by chronic periodontal disease with periodontal probing depth (PPD) ≥ 5 mm were treated with SRP plus local chlorhexidine. In each patient, similar teeth, treated with SRP with the adjunctive use of chlorhexidine digluconate and dihydrochloride or chlorhexidine gluconate, respectively, were selected and assigned to a test and a control group. In both groups, PPD, bleeding on probing (BOP) parameters, total bacterial counts (TBC) and quality of periodontal bacteria at time 0 and 6 weeks after treatment were measured. RESULTS: PPD significantly decreased over time both in the test and in the control group; however, no significant differences between the two groups were observed. BOP and TBC were significantly lower in the test than in the control group 6 weeks after treatment. In the post-treatment revaluation, a significant decrease both in the treatment and in the control group, for each of the single periodontal pathogens, was observed. CONCLUSION: In this study--a preliminary case series with small sample size and short follow-up--the adjunctive use of chlorhexidine (CHX) to SRP resulted in clinical and microbiological benefits in the treatment for generalized chronic periodontitis. A CHX gel formulation consisting of CHX digluconate and CHX dihydrochloride seems to lead some additional benefits over SRP plus CHX gluconate in the short term. Additional investigations are needed to evaluate the effectiveness of this antiseptic therapy.

Role of carbon monoxide and biliverdin in renal ischemia/reperfusion injury.

Heme oxygenase (HO) isoforms catalyze the conversion of heme to carbon monoxide (CO) and biliverdin/bilirubin with a concurrent release of iron. There is strong evidence that HO activity and products play a major role in renoprotection, however the exact molecular mechanisms underlying the beneficial effects exerted by this pathway are not fully understood. This review is aimed at illustrating the possible mechanism/s by which HO is renoprotective in the context of ischemia/reperfusion. We will first analyze the effects of exogenous administration of bilirubin/biliverdin and CO and then describe their biological activities once generated endogenously following stimulation of the HO pathway by either pharmacological means or gene targeting-mediated approaches.

Non protein bound iron concentrations in amniotic fluid.

OBJECTIVES: To investigate whether amniotic fluid concentrations of non protein bound iron (NPBI) vary with growth in healthy fetuses and also offer a reference curve in the second trimester of pregnancy. DESIGN AND METHODS: Amniotic fluid concentrations of NPBI were measured by HPLC in 118 women with physiological singleton pregnancies, who underwent amniocentesis for fetal karyotype between weeks 15 and 18 of gestation. RESULTS: NPBI increased progressively from weeks 14--15 to weeks 15--16, peaking at 17--18 weeks of gestation. NPBI values regressed positively with gestational age (GA). Multiple linear regression analysis between NPBI, as dependent variable, and various fetal parameters, as independent variables, showed a statistically significant regression coefficient with GA, bi-parietal diameter and transverse cerebellar diameter. CONCLUSIONS: The present data constitutes the first quantification of NPBI concentrations in amniotic fluid under physiological conditions. Correlations with GA and ultrasound fetal biometry suggest that NPBI may play a role in fetal growth.

Predictors of Ominous Outcome in Infants Undergone to Cardiac Surgery and Cardiopulmonary by-Pass: S100B Protein.

S100B protein has been recently proposed as a consolidated marker of brain damage and death in adult, children and newborn patients. The present study evaluates whether the longitudinal measurement of S100B at different perioperative time-points may be a useful tool to identify the occurrence of perioperative early death in congenital heart disease (CHD) newborns. We conducted a case-control study in 88 CHD infants, without pre-existing neurological disorders or other co-morbidities, of whom 22 were complicated by perioperative death in the first week from surgery. Control group was composed by 66 uncomplicated CHD infants matched for age at surgical procedure. Blood samples were drawn at five predetermined time-points before during and after surgery. In all CHD children, S100B values showed a pattern characterized by a significant increase in protein's concentration from hospital admission up to 24-h after procedure reaching their maximum peak (P<0.01) during cardiopulmonary by-pass and at the end of the surgical procedure. Moreover, S100B concentrations in CHD death group were significantly higher (P<0.01) than controls at all monitoring time-points. The ROC curve analysis showed that S100B measured before surgical procedure was the best predictor of perioperative death, among a series of clinical and laboratory parameters, reaching at a cut-off of 0.1 µg/L a sensitivity of 100% and a specificity of 63.7%. The present data suggest that in CHD infants biochemical monitoring in the perioperative period is becoming possible and S100B can be include among a series of parameters for adverse outcome prediction.

Elevated S100 blood level as an early indicator of intraventricular hemorrhage in preterm infants. Correlation with cerebral Doppler velocimetry.

The aim of this study was to assess the use of S100 protein in blood as a means of identifying preterm infants at risk of intraventricular hemorrhage. In 25 preterm newborns, S100 blood concentrations were measured by an immunoradiometric assay during the first 48 h. Cerebral Doppler velocimetry waveform patterns were also tested at the time the blood sample was taken, when clinical and cerebral ultrasound scanning were still normal. Of the 25 newborns studied, 14 were controls and 11 developed intraventricular hemorrhage as revealed by ultrasound scanning more than 72 h after birth, and clinically confirmed by neurological examination on the seventh day of follow-up. S100 blood concentrations were significantly higher (P<0.002) in infants with intraventricular hemorrhage than in control infants and also correlated significantly (r=0.81, P<0.003) with the grade of hemorrhage. A significant correlation (r=0.70, P<0.05) between the S100 blood concentration and the middle cerebral artery pulsatility index was also observed. The present data show that S100 blood concentrations offer a measurable parameter of brain lesion in preterm infants before a radiological assessment of hemorrhage can be performed, when clinical symptoms may be silent and preventive/therapeutic action could be especially useful.

Pregnancy-induced hypertension, antihypertensive drugs and the development of fetal behavioural states.

In 21 pregnancies complicated by pregnancy-induced hypertension (PIH) which was treated by antihypertensive drugs (labetalol, nifedipine), fetal behavioural recordings (quiet state, C1F; active state, C2F; no coincidence, NOC) and Doppler measurements of blood flow velocity in the umbilical artery (UA) (resistance index, RI) were made on two occasions (27-32 and 33-36 weeks of gestation). Data were compared to those of a control group of normally grown fetuses (n = 96); in 15 cases we were able to match fetuses from the study group for age (+/- 1 week) and weight (+/- 150 g) at birth with fetales from a control group. It was the aim of this study to investigate if there are disturbances in the development of fetal behavioural states and if possible disturbances are due to poor fetal growth or to antihypertensive therapy. Our results show that in PIH treated by antihypertensive drugs, there are disturbances in the development of fetal behavioural states with higher percentages of NOC and C1F, lower percentages of C2F, and higher UA RI values. These disturbances are mainly due to coexisting placental impairment and poor fetal growth rather than to nifedipine or labetalol therapy, although these drugs may cause some redistribution of states.

Doppler velocimetry and behavioural state development in relation to perinatal outcome in pregnancies complicated by gestational diabetes.

Seventy-one pregnancies complicated by gestational diabetes and 100 healthy pregnancies were monitored on two occasions (between 27th-32nd and 33rd-36th week of gestation) by behavioural state analysis (1F coincidence; 2F coincidence) and umbilical artery Doppler velocimetry (UA) (Resistance Index, RI). The purpose of our study was to determine if the development of behavioural states and Doppler velocimetry: (1) differ between normal and gestational diabetic cases; (2) in gestational diabetic cases, are they related to the degree of abnormality of the maternal oral glucose tolerance test (OGTT)?; and (3) are they predictors of perinatal outcome? (i.e. emergency caesarean section; low Apgar scores; respiratory distress syndrome; neonatal hypoglycaemia and neurological abnormality in the neonate and/or at 4 months of age). Our findings suggest that: (1) results on behavioral state development and Doppler velocimetry were significantly different in gestational diabetic cases; (2) infants of women with gestational diabetes who are neurologically abnormal during the newborn period, had a poor development of coincidence 2F during fetal life and had neonatal hypoglycaemia more often than infants with a normal neurological outcome; (3) in cases with abnormal neurological outcome, the maternal diabetes was more severe than in those cases with normal outcome.

Behavioural development and Doppler velocimetry in relation to perinatal outcome in small for dates fetuses.

Twenty-two small for dates (SFD) fetuses and 96 fetuses from uncomplicated pregnancies were monitored on two occasions between 27 and 32 weeks and the second time between 33 and 36 weeks of gestation by studying the development of behavioural states (coincidence 1F and 2F; no coincidence) and umbilical artery Doppler waveform patterns (UA; Resistance Index, RI). Data were related to neurological outcome at 8 months after birth. The purpose of this study was to investigate if the development of behavioural state is disturbed in SFD fetuses and if SFD fetuses who needed to be delivered early and/or had abnormal neurological outcome showed different state development and RI than SFD fetuses delivered later in pregnancy or with normal neurological outcome. Finally, we studied if there was a relationship between state development and RI. At 27-32 weeks of gestation the percentage of coincidence 2F (C2F%) was lower and the percentage of coincidence 1F (C1F%) and no coincidence (NOC%) were higher in the SFD fetuses than in the control group. At 33-36 weeks C2F% was lower and NOC% was higher but not statistically different (P = 0.2 and P = 0.07, respectively). SFD fetuses who needed to be delivered early had poorer state development than SFD fetuses at lower risk and infants who were abnormal at 8 months of life showed a higher C1F% and lower C2F% at 27-32 weeks. There were significant correlations between RI on the one hand and NOC% (r = 0.62) and C2F% (r = -0.48) on the other hand at 27-32 weeks in the subgroup with abnormal neurological outcome. In conclusion, in SFD fetuses there are disturbances in the development of behavioural states as well in the distribution of the periods of coincidence (with a decrease in C2F% and an increase in C1F%). Poorest state development is present in SFD fetuses at highest risk and in this group there appears to be a significant relationship between the degree of utero-placental insufficiency (RI) and disturbances in behavioural development.

S100B protein cord blood levels and development of fetal behavioral states: a study in normal and small-for-dates fetuses.

OBJECTIVE: We aimed to determine whether S100B protein levels in cord blood and the development of fetal behavioral states were altered and interrelated in small-for-dates (SFD) fetuses. METHODS: Umbilical cord blood samples were collected from 12 SFD fetuses with normal umbilical artery (UA) Doppler findings, from six SFD fetuses with abnormal Doppler waveform patterns and from 36 controls matched for gestational age. S100B protein levels were measured by means of a specific radioimmunoassay. Fetal behavioral state recordings were made before delivery by Cesarean section and data were expressed as percentage of quiet sleep coincidence (C1F), of activity state coincidence (C2-4F) and of no coincidence (NOC). Flow velocimetry waveforms were recorded from the uterine artery, UA and fetal middle cerebral artery (MCA). RESULTS: Mean S100B protein levels in umbilical plasma were significantly higher in the six SFD infants with abnormal prenatal Doppler findings (3.31 +/- 0.65 microg/l) than in SFD infants with normal Doppler findings (1.56 +/- 0.35 microg/l) and in controls (1.23 +/- 0.43 microg/l). Similarly in these fetuses NOC was higher and C2F significantly lower (p < 0.05), but there was no significant difference in C1F. S100B concentrations were correlated with the UA pulsatility index (PI) (r = 0.78, p < 0.01), with the MCA PI (r = -0.78, p < 0.01) and with the UA PI/MCA PI ratio (r = 0.80, p < 0.01). Also, NOC and C2F percentages were correlated with the UA PI (r = 0.61, p < 0.01 and r = -0.61, p < 0.01, respectively), with the MCAPI (r = -0.72, p < 0.001 and r = 0.66, p < 0.01, respectively), and with the UA PI/MCA PI ratio (r = 0.60, p < 0.01 and r = -0.54, p < 0.05, respectively). NOC was also correlated with S100B protein (r = 0.48, p < 0.05); the correlation of S100B protein and C2F almost reached significance (r = -0.47, p < 0.05). CONCLUSIONS: This study provides evidence of a relationship between a biochemical marker of brain development and/or integrity and the development of fetal behavioral states, offering additional information on brain maturation in normal and high-risk pregnancies.

Acute and chronic immunomodulatory changes in rat liver after fetal and perinatal asphyxia.

Hypoxic-ischemic encephalopathy (HIE) caused by fetal and perinatal asphyxia is an important cause of mortality in the neonatal period. Not only will asphyxia affect the brain but also other organs such as the liver and kidneys. Interestingly, it has been shown that liver damage is proportional to the severity of the asphyctic insult, implying an association between liver impairment and HIE. Accordingly, we investigated in an established rat model the acute and chronic hepatic response to both fetal (FA) and perinatal asphyxia (PA). In addition, we assessed whether fetal asphyctic preconditioning (PC) would have any beneficial effect on the liver. Inflammation, ceramide signaling and hepatocellular damage were analyzed in the livers of newborn and adult rats at several short- and long-term time points after both FA and PA. We found that although FA induced an acute inflammatory response, apoptotic mRNA levels and oxidative DNA damage were decreased at 96 h post FA. Whereas increased IL-6 and IL-10 mRNA levels were observed after PA, the combination of FA and PA (PC) attenuated the inflammatory response. Moreover, 6 h after PA anti-apoptotic genes were downregulated and associated with less lipid peroxidation, while preconditioned animals were comparable to controls. In summary, asphyctic PC seems to have an acute protective effect on the liver by modulating the inflammatory, apoptotic and anti-oxidative response. More insight into the hepatic response to asphyxia is necessary, as disturbed hepatic function is associated with metabolic diseases in later life.

Selective serotonin reuptake inhibitors in pregnancy.

The use of antidepressant drugs, such as selective serotonin reuptake inhibitors (SSRIs), during pregnancy is rapidly increasing. To date, the effects of SSRI on pregnant women and fetuses are controversial and still a matter of debate. Although a number of studies have shown that these antidepressants are not teratogenic, some of them have reported an increase of congenital malformations after antenatal exposure to SSRIs. Moreover, fetal behavior is affected by these drugs, 30% of infants suffer from neonatal withdrawal symptoms and long term sequelae have not yet been excluded. Since there are no clear guidelines for SSRI treatment in pregnancy, potential risks must be balanced against the effects of untreated maternal depression. Treatment with SSRIs before and during pregnancy should only be considered in case of real necessity. Milder forms of depression should be treated with alternative methods. In this paper we have reviewed the literature on effects of SSRIs on embryonic, fetal and infant development.

[Markers of brain injury in non-invasive biological fluids]. / Markers of brain injury in non-invasive biological fluids.

Hypoxia-ischemia (H-I) constitutes the main phenomenon responsible for brain-blood barrier permeability modifications leading to cerebral vascular autoregulation loss in newborns. Hypotension, cerebral ischemia, and reperfusion are the main events involved in vascular auto-regulation loss leading to cell death and tissue damage. Reperfusion could be critical since organ damage, particularly of the brain, may be amplified during this period. An exaggerated activation of vasoactive agents, of calcium mediated effects could be responsible for reperfusion injury (R-I), which, in turns, leads to cerebral hemorrhage and damage. These phenomena represent a common repertoire in newborns complicated by perinatal acute or chronic hypoxia treated by risky procedures such as mechanical ventilation, nitric oxide supplementation, brain cooling, and extracorporeal membrane oxygenation (ECMO). Despite accurate monitoring, the post-insult period is crucial, as clinical symptoms and standard monitoring parameters may be silent at a time when brain damage is already occurring and the therapeutic window for pharmacological intervention is limited. Therefore, the measurement of circulating biochemical markers of brain damage, such as vasoactive agents and nervous tissue peptides is eagerly awaited in clinical practice to detect high risk newborns. The present article is aimed at investigating the role of dosage biochemical markers in non-invasive biological fluids such as S100B, a calcium binding protein, activin A, a protein expressed in Central nervous System (CNS).

Antioxidant properties of anesthetics: the biochemist, the surgeon and the anesthetist.

General anesthesia can impair immunological defense mechanisms while inducing an inflammatory reaction. Generalized inflammatory reactions involve leucocytes which in turn release inflammatory mediators and free oxygen radicals. General anesthetics include a series of gaseous and intravenous sedative-hypnotic agents indicated for induction and maintenance of general anesthesia as well as for sedation of intubated, mechanically ventilated adults in intensive care units (ICU). Some anesthetics, such as propofol, are characterized by a phenolic structure similar to that of alpha-tocopherol, and exhibit antioxidant properties that have been demonstrated both in vitro and in vivo. Similarly, other anesthetics show antioxidant and protective roles but this mechanism is to be related to their ability to induce antioxidant enzyme (i.e., heme oxygenase-1). The aim of the present review is to evaluate the antioxidant properties of anesthetics in various experimental models and if they may be considered efficient therapeutic tools in counteracting oxidative stress during general anesthesia and sedation in ICU.

Nitric oxide test during cardiac catheterization decreases the serum concentrations of S100B protein in adult patients with idiopathic pulmonary hypertension.

OBJECTIVE: Cardiac catheterization (CC) is a life-threatening procedure in adult patients. Complicated by idiopathic arterial pulmonary hypertension (IPAH), there is a potential risk of central nervous system (CNS) damage. We measured serum levels of a well-established brain damage marker, namely S100B, collected before, during and after CC in adult patients in whom the nitric oxide (NO) test had been performed. MATERIAL AND METHODS: In 12 adult patients who had undergone CC for IPAH diagnosis, we recorded clinical and standard monitoring procedures (laboratory variables and echocardiographic patterns) and serum concentrations of S100B before (time 0), during (time 1) and after the NO test (time 2) and at 24 h after (time 3) the procedure in samples obtained from the systemic and pulmonary circulation. Patients were subdivided into NO test responders (n=6) and non-responders (n=6). Neurological evaluation was performed at admission and at discharge from hospital. RESULTS: Adult patients subjected to CC showed no overt neurological injury at discharge from hospital. No significant differences (p > 0.05 for all) in S100B serum levels between groups at times 0, 1 and 3 have been shown independently from the sampling site. It was noteworthy that the concentration of protein in the responders group at time 2 was significantly decreased (p < 0.05, for all) compared to the responder group and to baseline values. A significant correlation was found between arterial oxygen partial pressure and individual S100B concentration in the pulmonary and systemic bloodstream in the entire study group (R = -0.66 and R = 0.71, respectively; p < 0.05, for both). CONCLUSIONS: The data suggest that S100B protein assessment, as well as the NO test, may be useful when monitoring possible CNS damage during CC in patients with IPAH, and may also be valuable in relation to brain functions, especially when performed as an emergency procedure in severely hypoxic patients.

Kangaroo care improves post-extubation cardiorespiratory parameters in infants after open heart surgery.

UNLABELLED: The aim of this investigation was to study whether kangaroo care could be helpful in full-term infants subjected to cardiac postoperative intensive care during the early post-extubation hours. Kangaroo care was performed at 2-h intervals in the first 12 h after extubation in 5 male infants and assessed by cardiorespiratory parameters. Results showed that, during kangaroo care, heart rate (123 +/- 4 vs 128 +/- 5 bpm), respiratory frequency (43 +/- 3 vs 51 +/- 5 breath pm), transcutaneous carbon dioxide (46 +/- 2 vs 50 +/- 4 mmHg) and central venous pressure (11 +/- 0.8 vs 12 +/- 1.2 mmHg) significantly decreased (p <0.05 for all), while oxygen saturation (78 +/- 6 vs 74 5 mmHg) and transcutaneous oxygen pressure increased (42 +/- 2 vs 38 +/- 3 mmHg) (p < 0.05 for all). CONCLUSION: We conclude that kangaroo care might be a useful technique contributing to stabilization of the cardiorespiratory status in postoperative paediatric cardiac intensive care.

Adrenomedullin is increased in the fetoplacental circulation in intrauterine growth restriction with abnormal umbilical artery waveforms.

OBJECTIVE: To examine whether adrenomedullin, a novel vasoactive peptide produced by the placenta, participates in the uteroplacental hemodynamic alterations in intrauterine growth restriction, we studied the correlation between adrenomedullin levels and fetoplacental blood flow. STUDY DESIGN: Maternal and umbilical blood samples were collected in pregnancies complicated by intrauterine growth restriction with abnormal umbilical artery Doppler findings and in control pregnancies. Adrenomedullin levels were measured by means of a specific radioimmunoassay, and flow velocimetry waveforms were recorded from uterine, umbilical, and fetal middle cerebral arteries. RESULTS: Mean adrenomedullin values in umbilical plasma were higher (P <.05) in patients with intrauterine growth restriction (63.7 +/- 34.2 pg/mL; n = 16) than in control subjects (38.1 +/- 14.8 pg/mL; n = 16). A significant correlation was found between maternal adrenomedullin levels and umbilical artery pulsatility index. Moreover, fetal adrenomedullin concentrations correlated negatively with middle cerebral artery pulsatility index and positively with umbilical artery pulsatility index/middle cerebral artery pulsatility index ratio. CONCLUSION: This study provides evidence that adrenomedullin is increased in fetuses with intrauterine growth restriction in response to reduced uteroplacental blood flow and suggests that it may participate in the fetal hemodynamic modifications.

Circulating adrenomedullin is increased in preterm newborns developing intraventricular hemorrhage.

Adrenomedullin is a novel vasoactive peptide that participates in cerebral blood flow regulation and circulates in human plasma. To verify whether plasma adrenomedullin is able to identify preterm newborns at risk of intraventricular hemorrhage (IVH), we performed a case-control study. Plasma samples collected within 6 h after birth in 24 preterm newborns who developed IVH, as diagnosed at 72 h, were assessed for adrenomedullin and compared with those obtained from 48 preterm newborns, matched for gestational age, who did not develop IVH. Cerebral ultrasound and Doppler velocimetry waveform patterns in the middle cerebral artery were also recorded at the time of blood sampling. Adrenomedullin blood concentrations and middle cerebral artery pulsatility index values were significantly higher in infants developing IVH (20.1 +/- 4.5 fmol/mL and 1.71 +/- 0.21 fmol/mL, respectively) than in controls (7.5 +/- 3.0 fmol/mL and 1.49 +/- 0.19 fmol/mL, respectively). Adrenomedullin blood concentrations correlated with middle cerebral artery pulsatility index (r = -0.77, p < 0.01) and with the grade of IVH extension (r = 0.83, p < 0.01). This study suggests that adrenomedullin blood concentration might be a promising tool for identifying preterm infants at risk of IVH immediately after birth, when imaging assessment and clinical symptoms of hemorrhage are still silent.

Phentolamine administration increases blood S100B protein levels in pediatric open-heart surgery patients.

AIM: Phentolamine administration during open-heart surgery shortens the cooling and rewarming phases of cardiopulmonary bypass (CPB) and hastens weaning from mechanical ventilation and extubation. Data on the effects of phentolamine on cerebral circulation and function in this setting are lacking. This study reports the cerebral effects of phentolamine using blood S100B protein levels and the middle cerebral artery pulsatility index (MCA PI). METHODS: Sixty pediatric patients undergoing congenital heart disease repair were randomly assigned to receive either phentolamine 0.2 mg kg(-1) i.v. (n = 30) or placebo (n = 30) before the cooling and rewarming phases of CPB. Samples for S100B measurement were collected at seven predetermined time-points before, during and after surgery. MCA PI values were recorded at the same times as sampling. RESULTS: S100B blood levels were higher in the phentolamine-treated group than in controls after rewarming (3.53 +/- 1.88 vs 1.58 +/- 0.53 microg l(-1); p < 0.001), remained persistently higher at the end of surgery (2.95 +/- 0.91 vs 0.79 +/- 0.21 microg l(-1); p < 0.001) and returned to normal ranges 12 h later than in the placebo group (p > 0.05). MCA PI values were also significantly higher at the end of surgery in the phentolamine-treated group (1.83 +/- 0.50 vs 1.22 +/- 0.34; p < 0.01). Cooling and rewarming times were shorter in the phentolamine-treated group (p < 0.01, for all). CONCLUSION: Despite improved peripheral vasodilatation and perfusion, phentolamine administration in pediatric open-heart surgery is correlated with increased cerebrovascular resistance and brain damage.