Biomedical subjects

F van Bel

Publications and source records attributed to F van Bel.

At least 19 recordsLinked to original sources

PubMed2001

Neonatal dexamethasone treatment induces long-lasting changes in T-cell receptor vbeta repertoire in rats.

Glucocorticoids are frequently administered for the prevention of chronic lung disease in infants with respiratory distress syndrome. However, neonatal treatment may have consequences for immune functioning in the long-term. Here we demonstrate that neonatal glucocorticoid treatment has long-lasting effects on mRNA expression of several Vbeta genes within the CD4 and CD8 T cell subset in rats. Changes in the peripheral T cell Vbeta repertoire may be a consequence of altered intrathymic selection events in which corticosterone plays an important role. Indeed, here we show that neonatal glucocorticoid treatment affects corticosterone production by thymic epithelial cells during neonatal life. In conclusion, changes in T cell Vbeta repertoire after neonatal glucocorticoid treatment may contribute to altered immune reactivity in later life.

Age Factors↗

PubMed2001

Neonatal glucocorticoids and the developing brain: short-term treatment with life-long consequences?

Although synthetic glucocorticoids are frequently used in hospital for the prevention of chronic lung disease in premature infants, major concern has arisen about the possible long-term consequences of these treatments. Animal research provides evidence for the idea that neonatal glucocorticoid treatment enhances susceptibility to autoimmune disease in adult life. Altered functioning of the hypothalamo-pituitary-adrenal axis, and/or changes at higher brain levels might underlie alterations in disease susceptibility.

Animals↗

PubMed2001

Inhibition of nitric oxide synthesis following severe hypoxia-ischemia restores autoregulation of cerebral blood flow in newborn lambs.

Birth asphyxia impairs the autoregulatory ability of the cerebral blood flow. Inappropriate synthesis of vasodilatory nitric oxide may be important in this respect. We investigated if nitric oxide synthesis inhibition by N(omega)-nitro-L-arginine (NLA) could restore cerebral autoregulation after severe hypoxia-ischemia (HI). HI was induced in 15 newborn lambs. Cerebral blood flow (carotid artery blood flow [ml/min]: Qcar) and mean aortic blood pressure [mmHg]: MABP) were measured over a 30 min period before HI (pre-HI), 0-30 min after completion of HI (0-30 post-HI) and from 60 to 120 min post-HI (60-120 post-HI). Immediately after completion of HI, 5 lambs received a placebo (PLAC), 5 low dose NLA (10 mg/kg/iv: NLA-10) and 5 high dose NLA (40 mg/kg/iv: NLA-40). Pre-HI, all groups showed cerebral autoregulation with an upper limit of regulatory ability between 75 and 90 mm Hg. At 0-30 post-HI, all groups lacked autoregulatory ability of the cerebral vascular bed and showed an aortic blood pressure-passive Q(car). At 60-120 post-HI autoregulation was restored in NLA-10 and NLA-40-treated lambs (upper limit of autoregulation was shifted to higher MABP in NLA40-treated lambs), but not in placebo-treated lambs. At 60-120 post-HI MABP was higher in both NLA-groups than in PLAC group (83+/-15 [NLA-10] and 78+/-14 [NLA-40] vs. 65+/-9 mmHg [PLAC], P<0.05). We conclude that severe HI in newborn lambs induces impairment of the autoregulatory ability of the cerebral vascular bed. Even low-dose nitric oxide-synthesis inhibition started upon reperfusion restored autoregulation, suggesting a role for nitric oxide-induced vasodilation in the impairment of autoregulation of the cerebral blood flow after birth asphyxia.

Animals↗

PubMed2001

Endothelin-1 plasma concentration increases in the early phase of pulmonary hypertension development during respiratory distress syndrome: a study in newborn lambs.

OBJECTIVE: Elevated plasma concentrations of endothelin-1 (ET-1) have been reported with pulmonary hypertension during respiratory distress syndrome (RDS). However, the exact role of ET-1 in the development of pulmonary hypertension during RDS is unclear. The relative time-course of changes in ET-1 concentrations and pulmonary artery pressure (P(ap)) during RDS may give insight in the role of ET-1. METHODS: ET-1 and P(ap) changes were studied in an experimental model of RDS, induced by lung lavages in seven newborn lambs. Five other lambs served as controls. RESULTS: Lung lavages induced a twofold increase of mean P(ap) (from 15 to 34 mm Hg) that remained present throughout the 4-h study period. Along with the increased P(ap), ET-1 plasma concentration showed a significant increase 15 min after induction of RDS at all three sample locations (pulmonary artery 198%, aorta 181% and right atrium 195% compared to baseline). This increased concentration remained high at 1 and 4 h of RDS. In control animals, no significant changes in ET-1 concentrations were observed. Plotting ET-1 concentration values against mean P(ap), in RDS and control animals at all time points, a correlation was found between the severity of the pulmonary hypertension and ET-1 concentration. CONCLUSION: This experimental model of RDS shows that ET-1 concentration increases concomitant with the development of pulmonary hypertension, from an early time point onward. More severe pulmonary hypertension is associated with higher ET-1 concentrations, but whether ET-1 is a marker or a mediator of pulmonary hypertension remains as yet unsettled.

Animals↗

PubMed2001

Pharmacotherapeutical reduction of post-hypoxic-ischemic brain injury in the newborn.

Perinatal hypoxia-ischemia (PHI) is a major cause of morbidity and mortality. A substantial part of PHI-related brain damage occurs upon reperfusion and reoxygenation by the excess production of excitatory amino acids, free (pro)radicals and the release of cytokines, triggering programmed cell death. In this respect, several neuroprotective agents have been investigated in neonatal animal models, providing evidence for their usefulness in PHI. Several agents have been shown to be neuroprotective in neonatal animal hypoxia-ischemia models, but only a few agents have been used in clinical studies on term newborns. Although some general information will be provided with respect to focal hypoxia-ischemia and neuroprotective agents, this paper focuses on the investigated neuroprotective agents for global PHI and reperfusion brain injury in the newborn, categorized by their mode of action. Future experimental and clinical trials with promising neuroprotective agents need to be performed, including long-term follow-up to monitor long-term consequences. Moreover, well-designed combinations of neuroprotective agents with or without other neuroprotective strategies such as brain hypothermia should be given consideration for producing the most promising results in reducing post-hypoxic-ischemic reperfusion injury of the newborn brain.

Apoptosis↗

PubMed2001

Nitric oxide production during the early neonatal period in small-for-gestational-age infants.

UNLABELLED: In a study of endogenous nitric oxide production in growth-retarded, very preterm newborns (<32 wk GA), urinary NOx/creatinine ratio and plasma guanosine 3',5'-cyclic monophosphate levels were determined during the early neonatal period. Newborns were divided into three groups: appropriate-for-gestational-age (AGA, n = 19), moderately small-for-gestational-age (SGA, n = 13) and severely SGA (n = 6) infants. Severely SGA infants showed significant higher values of nitric oxide derivatives during the first 24 h of life compared with the other groups. CONCLUSION: An increased NO production is found in SGA infants during the first 24 h after birth. This may reflect an increased intrauterine nitric oxide production in the feto-placental circulation found in cases with intrauterine growth retardation,

Analysis of Variance↗

PubMed2000

Neonatal dexamethasone treatment increases susceptibility to experimental autoimmune disease in adult rats.

Major concern has emerged about the possible long term adverse effects of glucocorticoid treatment, which is frequently used for the prevention of chronic lung disease in preterm infants. Here we show that neonatal glucocorticoid treatment of rats increases the severity (p< or = 0.01) and incidence (p< or =0.01) of the inflammatory autoimmune disease experimental autoimmune encephalomyelitis in adult life. In search of possible mechanisms responsible for the increased susceptibility to experimental autoimmune encephalomyelitis, we investigated the reactivity of the hypothalamo-pituitary-adrenal axis and of immune cells in adult rats after neonatal glucocorticoid treatment. We observed that neonatal glucocorticoid treatment reduces the corticosterone response after an LPS challenge in adult rats (p< or =0.001). Interestingly, LPS-stimulated macrophages of glucocorticoid-treated rats produce less TNF-alpha and IL-1beta in adult life than control rats (p<0.05). In addition, splenocytes obtained from adult rats express increased mRNA levels of the proinflammatory cytokines IFN-gamma (p<0.01) and TNF-beta (p<0.05) after neonatal glucocorticoid treatment. Apparently, neonatal glucocorticoid treatment has permanent programming effects on endocrine as well as immune functioning in adult life. In view of the frequent clinical application of glucocorticoids to preterm infants, our data demonstrate that neonatal glucocorticoid treatment may be a risk factor for the development of (auto)immune disease in man.

Aging↗

PubMed2000

Cerebral blood flow velocity wave form as an indicator of neonatal left ventricular heart function.

OBJECTIVE: To investigate the relationship between cerebral blood flow velocity wave form (CBFV-WF) parameters and myocardial contractility indices in healthy and sick preterm and term newborns. METHODS: Total group of 82 babies was divided into four subgroups: prematures with gestational age <34 weeks with (n=20) and without (n=14) respiratory distress syndrome (RDS) and infants with gestational age of >33 weeks with (n=18) and without (n=30) asphyxia. On day 1, 2, 3, 6 and 14, the acceleration time, Q(ECG)-peak(flow) time and preejection period of CBFV-WF (internal carotid artery) were measured through the anterior fontanel by Doppler ultrasonography. Simultaneously cardiac output, fractional shortening, systolic time intervals and their ratio were determined echocardiographically. RESULTS: RDS-babies had higher cardiac output and better myocardial performance then non-RDS-babies. Asphyxiated babies had lower cardiac output as compared to healthy babies, improving over time. Correlations were found between CBFV-WF parameters and several myocardial function indicators, but preejection period of cerebral blood flow velocity correlated closest with the same period measured echocardiographically (r=0.67, P<0.0001). Multiple linear regression revealed no influence of gestational age or clinical condition on this relationship. Assessment of agreement indicated that only substantial changes in myocardial performance could be monitored using preejection period of CBFV. CONCLUSION: Although a relationship was detected between the preejection period of CBFV and left ventricular systolic time interval (used as indicator of changes in left ventricular function), only rather large changes in left ventricular performance can be reliably detected using the preejection period of CBFV.

Aorta, Thoracic↗

PubMed2000

Improved contractile performance of right ventricle in response to increased RV afterload in newborn lamb.

Pulmonary hypertension results in an increased afterload for the right ventricle (RV). To determine the effects of this increased afterload on RV contractile performance, we examined RV performance before and during 4 h of partial balloon occlusion of the pulmonary artery and again after releasing the occlusion in nine newborn lambs. RV contractile performance was quantified by indexes derived from systolic RV pressure-volume relations obtained by a combined pressure-conductance catheter during inflow reduction. An almost twofold increase of end-systolic RV pressure (from 22 to 38 mmHg) was maintained during 4 h. Cardiac output (CO) (0.74 +/- 0.08 l/min) and stroke volume (4.3 +/- 0.4 ml) were maintained, whereas end-diastolic volume (7.9 +/- 1.3 ml) did not change significantly during this period. RV systolic function improved substantially; the end-systolic pressure-volume relation shifted leftward indicated by a significantly decreased volume intercept (up to 70%), together with a slightly increased slope. In this newborn lamb model, maintenance of CO during increased RV afterload is not obtained by an increased end-diastolic volume (Frank-Starling mechanism). Instead, the RV maintains its output by improving contractile performance through homeometric autoregulation.

Animals↗

PubMed2000

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.

Blood Pressure↗

PubMed2000

Influence of inhibition of nitric oxide synthesis on cardiac function in the newborn lamb after hypoxic-ischemic injury.

The aim of the present study was to investigate the effect of immediate post-hypoxic-ischemic (HI) inhibition of nitric oxide synthesis by N(omega)-nitro-L-arginine (NLA) on cardiac function and reactive oxygen species production. Fifteen newborn lambs were subjected to severe HI. Upon resuscitation 5 received 10 mg NLA/kg, 4 40 mg NLA/kg and 6 a placebo. Left ventricular (LV) contractility, cardiac output (CO), non-protein-bound iron (NPBI), ratio of reduced/oxidized ascorbic acid, alpha-tocopherol, sulfhydryl groups and malondialdehyde were measured before and 15, 60 and 120 min after resuscitation. There was a significant decrease in CO in all 3 groups at 60 min post-HI (p < 0.05). Reactive oxygen species production was also highest at 60 min post-HI (significantly increased NPBI and decrease in sulfhydryl groups in control lambs; p < 0.05). These results suggest neither a positive nor a negative effect of nitric oxide synthesis inhibition on post-HI myocardial performance but may suggest a positive effect of NLA on reactive oxygen species-mediated post-HI damage.

Animals↗

PubMed2000

Effects of deferoxamine, a chelator of free iron, on NA(+), K(+)-ATPase activity of cortical brain cell membrane during early reperfusion after hypoxia-ischemia in newborn lambs.

Free iron chelation after hypoxia-ischemia can reduce free radical-induced damage to brain cell membranes and preserve electrical brain activity. We investigated whether chelation of free iron with deferoxamine (DFO) preserved cortical cell membrane activity of Na(+),K(+)-ATPase and electrocortical brain activity (ECBA) of newborn lambs during early reperfusion after severe hypoxia-ischemia. Hypoxia was induced in 16 lambs by decreasing the fraction of inspired oxygen to 0.07 for 30 min, followed by a 5-min period of hypotension (mean arterial blood pressure <35 mm Hg). ECBA (in microvolts) was measured using a cerebral function monitor. Immediately after hypoxia and additional ischemia, eight lambs received DFO (2.5 mg/kg, i.v.), and seven lambs received a placebo (PLAC). Two lambs underwent sham operation. One hundred eighty minutes after completion of hypoxia and ischemia, the brains were obtained and frozen. Na(+),K(+)-ATPase activity was measured in the P(2) fraction of cortical tissue. Na(+),K(+)-ATPase activity was 35.1 +/- 7.4, 42.0 +/- 7.6, and 40.7 +/- 1.4 micromol inorganic phosphate/mg protein per hour in PLAC-treated, DFO-treated, and sham-operated lambs, respectively (p < 0.05: DFO versus PLAC). ECBA was 11.2 +/- 6.1, 14.8 +/- 4.8, and 17.5+/-.0.5 microV in PLAC-treated, DFO-treated, and sham-operated lambs, respectively (p = 0.06: DFO versus PLAC). Na(+),K(+)-ATPase activity correlated with ECBA at 180 min of reperfusion (r = 0.85, p < 0.001). We conclude that Na(+),K(+)-ATPase activity of cortical brain tissue was higher in DFO-treated lambs compared with PLAC-treated animals during the early reperfusion phase after severe hypoxia-ischemia, suggesting a reduction of free radical formation by DFO. Furthermore, a positive relationship was found between Na(+),K(+)-ATPase activity and ECBA.

Animals↗

PubMed1999

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.

Blood Flow Velocity↗

PubMed1999

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.

Anesthesia↗

PubMed1999

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.

Carotid Artery, Internal↗

PubMed1999

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.

Animals↗

PubMed1998

Effect of deferoxamine and allopurinol on non-protein-bound iron concentrations in plasma and cortical brain tissue of newborn lambs following hypoxia-ischemia.

Reduction of non-protein-bound iron (NPBI) using iron chelators may attenuate hypoxia-ischemia-induced reperfusion injury of the brain. This study investigated whether administration of low-dose deferoxamine and allopurinol, both having NPBI-chelating properties, reduced hypoxia-ischemia-induced NPBI formation in plasma effluent from the brain and in cerebral cortical tissue. Twenty-one newborn lambs underwent severe hypoxia-ischemia. Upon reperfusion and reoxygenation the lambs received either a placebo (n = 7), or deferoxamine 2.5 mg/kg (n = 7) or allopurinol 20 mg/kg (n = 7). The post-hypoxic-ischemic NPBI levels in plasma were significantly lower after deferoxamine but not after allopurinol as compared to placebo-treated lambs. Cortical NPBI levels in both deferoxamine and allopurinol-treated lambs were significantly lower than NPBI levels in placebo-treated lambs. We conclude that deferoxamine effectively lowers NPBI in plasma effluent from the brain, and that both, deferoxamine and allopurinol, lower NPBI in cortical brain tissue.

Allopurinol↗

PubMed1998

[Nitric oxide inhalation in newborn infants with pulmonary hypertension].

Nitric oxide (NO) is an important endogenous vasodilator. NO, produced in the endothelial cell, causes vasodilation by relaxation of the vascular smooth muscle cell. Inhalation of NO plays a role in the treatment of persistent pulmonary hypertension of the newborn, a syndrome with considerable morbidity and mortality. NO inhalation specifically leads to pulmonary vasodilation without systemic hypotension, since NO binds avidly to haemoglobin. Neonates with pulmonary hypertension associated with lung hypoplasia, meconium aspiration syndrome, infantile inspiratory distress syndrome due to surfactant deficiency, and sepsis have been treated with inhaled NO. Literature data on NO inhalation and experience in our units with NO inhalation show an improvement in arterial oxygen tension and a decreased need for extracorporeal membrane oxygenation, but no reduction in mortality. NO toxicity as a result of NO inhalation in the newborn has not been reported yet.

Administration, Inhalation↗