Cerebral blood flow velocity in term newborn infants: changes associated with ductal flow

The effects of ductal closure on range-gated pulsed Doppler cerebral blood flow velocity (CBFV) patterns in the internal carotid, anterior cerebral, and middle cerebral arteries were studied in 10 normal term infants (mean birth weight 3302 +/- 294 g (SD) and mean gestational age 39.6 +/- 1.3 weeks). Pulsatility was calculated from flow velocities and used as an estimate of cerebral blood flow (CBF). Ductal closure was associated with a rise in mean blood pressure from 45.0 +/- 4.2 to 51.3 +/- 6.5 mm Hg (P less than 0.05) and a significant decrease in pulsatility in all three vessels (mean = 0.77 +/- 0.07 vs 0.70 +/- 0.05 (P less than 0.02]. Changes in pulsatility were correlated with changes in mean blood pressure (P less than 0.02), providing evidence that systemic blood pressure may influence postnatal cerebral arterial pulsatility indices. We also noted significant differences in the velocity and pulsatility of individual vessels that were independent of blood pressure, suggesting that Doppler flow studies may be useful in describing regional CBF patterns. The temporal association between ductal closure and decreased pulsatility suggests that CBFV patterns reflect ductal shunting in normal term newborn infants. Diastolic runoff and reduced systemic blood pressure in the presence of ductal shunting appear to reduce diastolic flow velocity and increase CBFV pulsatility in normal term infants during the first days of life. Normal mechanisms of cerebral autoregulation compensate for decreased flow with vasodilation; therefore the increased pulsatility associated with ductal shunting may be due to diastolic runoff rather than increased cerebrovascular resistance.     

Autoregulation of brain blood flow in the newborn piglet: regional differences in flow reduction during hypotension

The potential use of a piglet as a model for investigation of brain blood flow was evaluated by assessing the presence of autoregulation in 11 spontaneously breathing newborn piglets. Blood pressure was altered by phlebotomy. When the mean arterial blood pressure was greater than 50 mm Hg, no significant change in brain blood flow (microsphere technique) occurred (r = 0.04), indicating the presence of autoregulation. When the animals became hypotensive a pressure passive relationship exists between brain blood flow and mean arterial blood pressure. However, since the piglets breathed spontaneously and hyperventilated during hypotension, both the mean arterial blood pressure and PaCO2 fell and both correlated with brain blood flow. Thus, it cannot be determined which factor is responsible for the reduction in flow. The blood flow to the specific regions of the brain (cerebrum, cerebellum, brainstem) and mean arterial blood pressure also showed no correlation when the latter was greater than 50 mm Hg. During hypotension, each region demonstrates pressure passive relationships, but the reduction in blood flow is most pronounced in the cerebrum, less in the cerebellum, and least in the brainstem (mean +/- S.E., 64 +/- 8%, 41 +/- 13%, 32 +/- 13% reductions from control respectively, P less than 0.05). The study indicates that a newborn piglet may serve as an appropriate model for the study of brain hemodynamics particularly with regard to autoregulation. Furthermore, during hypotension, preferential protection of vital regions of the brain (cerebellum and brainstem) occur which may have important implications in interpreting the effect of hypotension on the newborn central nervous system.     

Intrauterine growth restriction ameliorates the effects of gradual hemorrhagic hypotension on regional cerebral blood flow and brain oxygen uptake in newborn piglets

Data are scant regarding the development of cerebrovascular autoregulation in intrauterine growth-restricted (IUGR) newborns. We tested the hypothesis that IUGR improves the ability of neonates to withstand critical periods of gradual hemorrhagic hypotension by optimizing cerebrovascular autoregulation. Studies were conducted on 1-d-old anesthetized piglets divided into groups of normal weight (NW, n = 14, body weight = 1518 +/- 122 g) and IUGR (n = 14, body weight = 829 +/- 50 g) animals. Physiologic parameters, including regional cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO(2)), were similar in NW and IUGR piglets under baseline conditions. Controlled arterial blood loss [hemorrhagic hypotension (HH)] induced a stepwise reduction of the mean arterial blood pressure of 49 +/- 3 mm Hg (mild HH), 39 +/- 3 mm Hg (moderate HH), and 30 +/- 3 mm Hg (severe HH) in seven NW and seven IUGR piglets (p < 0.05). In NW piglets, cortical CBF and CMRO(2) was reduced already at moderate HH (p < 0.05). A similar CMRO(2) reduction occurred during severe HH in NW and IUGR piglets (p < 0.05). In addition, during mild and moderate HH, primarily in IUGR piglets, an increase in regional CBF of brainstem, cerebellum, and thalamus was shown compared with baseline values (p < 0.05). Furthermore, under these conditions, cerebral cortex blood flow was maintained in newborn IUGR animals. In contrast, NW piglets exhibited a significant reduction in CBF (p < 0.05) during moderate HH. Thus, IUGR resulted in an improved ability to withstand critical periods of gradual oxygen deficit as shown by improved cerebrovascular autoregulation during hemorrhagic hypotension.     

Cerebral Doppler and misrepresentation of flow changes

To determine whether cerebral blood flow velocity (CBFV) measurements were representative of cerebral blood flow (CBF) changes in pathological flow situations five newborn piglets were investigated. They underwent measurements of CBF by electromagnetic flowmetry on a modified common carotid artery where extracerebral branches were tied off simultaneously with Doppler recording either from the same precerebral or an intracerebral artery. The two methods agreed well within moderate carbon dioxide and blood pressure changes. During severe hypotension and hypertension Doppler overestimated CBF by 25-100%. During transfusion of infected or incompatible blood the two methods differed in opposite directions with Doppler reading from 30-200% of CBF. Transfusion of chilled blood caused CBFV to overestimate 15% and heated blood caused 20% underestimation. These results could be explained by diameter changes in response to variation in myogenic tone or vasoactive substances. CBFV measurements could be seriously misleading in severe clinical derangements where neonatal brain damage might occur.     

Cerebral Doppler and misrepresentation of flow changes

To determine whether cerebral blood flow velocity (CBFV) measurements were representative of cerebral blood flow (CBF) changes in pathological flow situations five newborn piglets were investigated. They underwent measurements of CBF by electromagnetic flowmetry on a modified common carotid artery where extracerbral branches were tied off simultaneously with Doppler recording either from the same precerebral or an intracerebral artery. The two methods agreed well within moderate carbon dioxide and blood pressure changes. During severe hypotension and hypertension Doppler overestimated CBF by 25-100%. During transfusion of infected or incompatible blood the two methods differed in opposite directions with Doppler reading from 30-200% of CBF. Transfusion of chilled blood caused CBFV to overestimate 15% and heated blood caused 20% underestimation. These results could be explained by diameter changes in response to variation in myogenic tone or vasoactive substances. CBFV measurements could be seriously misleading in severe clinical derangements where neonatal brain damage might occur.     

Effects of partial plasma exchange transfusion on cerebral blood flow velocity in polycythaemic preterm,term and small for date newborn infants

Isovolemic haemodilution with plasma was performed in 36 newborn infants with polycythaemia 3 h after birth. Continuous wave Doppler ultrasonography was used to study the short and longer term influence of partial plasma exchange transfusion on cerebral blood flow velocity in both the anterior cerebral and mid cerebral arterial system up to 24 h after haemodilution. The study group consisted of 11 preterm infants, 12 term infants, and 13 small for date infants. After exchange transfusion peripheral venous haemotocrit decreased from 72.5% to 59.4%. In all experimental groups cerebral blood flow velocity (CBFV) before exchange transfution was significantly lower (18%–44%) than matched controls, and increased to control levels after exchange transfusion. CBFV improved most in preterm infants. After the transfusion the values were no different from the age-, weight-, sex-and parity-matched control groups, and they remained at this level during the next 24 h. No differences could be found between the anterior and mid-cerebral arterial system. When clinical symptoms were present, they subsided in all infants. In conclusion, partial plasma exchange transfusion has a favourable effect for at least 24 h on cerebral blood flow velocity in newborn infants with polycythaemia.Abbreviations AUC area under the curve (mean flow velocity) - CBFV cerebral blood flow velocity - EDFV end diastolic flow velocity - Hct haematocrit - PI pulsatility index according to Pourcelot - PRET partial plasma exchange transfusion - PSFV peak systolic flow velocity     

Blood flow distribution and brain metabolism during tolazoline-induced hypotension in newborn dogs

Tolazoline is used in neonatal intensive care to treat hypoxia secondary to persistent pulmonary hypertension of the newborn. Its use is often complicated by systemic hypotension. We compared the effect of tolazoline-induced hypotension on organ blood flow, regional brain blood flow, and cerebral metabolism in hypoxic newborn dogs whose mean arterial pressure fell by more than 20% with a second group whose blood pressure fell by less than 20%. Blood flows were measured by the radioactive microsphere technique. We found no changes in organ blood flow, regional brain blood flow, and cerebral metabolism in hypoxic animals whose mean arterial blood pressure decreased less than 20% during tolazoline administration. However, in those animals whose mean arterial blood pressure decreased more than 20%, we found a decrease in cerebral blood flow. As a consequence of decreased cerebral blood flow, cerebral oxygen delivery decreased. However, oxygen extraction increased so that cerebral metabolic rate was preserved.     

近红外光谱仪监测脑血流及血管自主调节功能的实验研究

目的评价近红外光谱仪（NIRS）脑氧合指标与新生猪脑血流的相关性,以寻找能最好反映脑血流变化及脑血管自主调节功能的NIRS指标。方法10头出生前1～3d新生猪随机分为两组：正常对照组（6头）、低血压组（4头）。人为动脉放血造成血压及脑血流的改变。应用NIRS连续监测脑组织氧合血红蛋白（△HbO2）与还原血红蛋白（△HHb）的动态变化,计算二者之和tHb（△tHb=△HbO2＋△HHb）．及二者之差△HbD（△HbD=△HbO2-△HHb）。同时应用彩色微球技术定量测定脑血流的变化,并对测定结果进行线性回归分析。结果对NIRS测定的△tHb、△HbD和彩色微球定量测得的全脑（GCBF）以及大脑皮层脑血流（CBFc）之间的关系进行线性回归分析。正常生理条件下,△HbD和△tHb与GCBF存在显著相关,相关系数分别为r1a=0．409和r1b=0．440,P均〈0．05;△HbD和△tHb与CBFc也存在显著相关,相关系数分别为r2a=0．394和r2b=0．400,P均〈0．05。低血压条件下,新生猪仅在M△BP降至35mmHg（1mmHg=0．133kPa）时脑血流才显著降低（P〈0．05）,而随着血压的逐渐降低,△HHb逐渐增高（P〈0．01）,△HbO,和△tHb先有升高趋势（P〈0．05）,然后在M△BP降至35mmHg时才显著降低（P〈0．01）,△HbD与GCBF、CBFc采用线性回归分析所得的相关系数r3a=0．890、r3b=0．887差异有统计学意义,P均〈0．01;而△tHb与GCBF、CBFc采用线性回归分析所得的相关系数r4a=0．395、r4b=0．375差异均无统计学意义,P均〉0．05,△HbD与脑血流的变化趋势相同,二者密切相关;而△tHb与脑血流的变化未存在相关。新生猪M△BP〉35mmHg时脑血流与血压不相关,提示自主调节功能完整,将调节功能完整的新生猪脑血流、△HbD与相应的M△BP值行线性回归分析显示相关系数〈0．5;M△BP〈35mmHg时脑血流与血压相关,提示自主调节功能受损,将调节功能受损的新生猪脑血流、△HbD与相应的M△BP值行线性回归分析显示相关系数〉0．5。结论正常生理及低血压条件下,△HbD均能很好反映出脑血流的动态变化;△tHb仅在正常生理条件下能用来反映脑血流的动态变化。1～3d新生猪脑血管自主调节的下限为35mmHg,NIRS氧合指标△HbD与M△BP的相关性可以反映新生猪的脑血管自主调节状态。     

Newborn piglets with meconium aspiration resuscitated with room air or 100% oxygen

We investigated whether newborn piglets exposed to hypoxemia and severe meconium aspiration could be reoxygenated with room air as efficiently as with 100% O(2). Twenty-one 2- to 5-d-old piglets were randomly divided into three groups: 1) the room air group: hypoxemia, meconium aspiration, and reoxygenation with room air (n = 8); 2) the O(2) group: hypoxemia, meconium aspiration, and reoxygenation with 100% O(2) (n = 8); and 3) the control group: meconium aspiration, and reoxygenation with room air (n = 5). Hypoxemia was induced by ventilation with 8% O(2) until the mean blood pressure reached <20 mm Hg or the base excess reached <-20 mM. At this point, reoxygenation was started with either room air or 100% O(2). Three milliliters per kilogram of meconium 110 mg/mL was instilled into the trachea immediately before the start of reoxygenation. The O(2) tension in arterial blood was significantly lower in the room air group; at 5 min of reoxygenation it was 9.1 +/- 0.5 kPa versus 43.5 +/- 6 kPa in the O(2) group (p < 0.05). At 5 min of reoxygenation the tidal volume per kilogram was 12.1 +/- 0.7 mL/kg in the room air group and 13.1 +/- 0.9 mL/kg in the O(2) group (NS). There were no significant differences between the room air and the O(2) groups during 120 min of reoxygenation in mean arterial blood pressure, pulmonary arterial pressure, cardiac index, base excess, or plasma hypoxanthine. In conclusion, hypoxic newborn piglets with meconium aspiration were found to be reoxygenated as efficiently with room air as with 100% O(2).     

Reoxygenation with 100 or 21% oxygen after cerebral hypoxemia-ischemia-hypercapnia in newborn piglets

We tested if reoxygenation with 100% O(2) was superior to 21% O(2) after combined cerebral hypoxemia-ischemia-hypercapnia (HIH) in newborn piglets. Twenty-eight piglets were randomized to reoxygenation with 100 or 21% O(2) following asphyxia. Asphyxia was induced by ventilation with 8% O(2), adding CO(2), and temporary occlusion of both common carotid arteries. After 20 min, reoxygenation-reperfusion was started with 21% O(2) (HIH 21% group, n = 13) or 100% O(2) (HIH 100% group, n = 11) for 30 min followed by 21% O(2). All piglets were observed for 2 h. We measured mean arterial blood pressure (MABP), changes in microcirculation in the cerebral cortex (laser Doppler), and extracellular concentrations of hypoxanthine in the cortex and amino acids in the striatum (microdialysis). We found significantly higher MABP and better restoration of microcirculation after reoxygenation with 100% compared with 21% O(2), but no differences in biochemical markers were found between the groups. This indicates that the brain tolerated reoxygenation with 21% as well as with 100% O(2) in the present model of experimental asphyxia in spite of the differences in MABP and cerebral microcirculation.     

Regional cerebral blood flow after hemorrhagic hypotension in the preterm, near-term, and newborn lamb

Developmental changes in regional cerebral blood flow (CBF) responses to hemorrhagic hypotension during normoxia and normocapnia were determined using radioactively labeled microspheres to measure flow to the cortex, brainstem, cerebellum, white matter, caudate nucleus, and choroid plexus in three groups of chronically catheterized lambs: 90- to 100-d preterm fetal lambs (n = 9); 125- to 136-d near-term fetal lambs (n = 9); and newborn lambs 5- to 35-d-old (n = 8). Heart rate, central venous pressure, and arterial blood pressure were monitored continuously and arterial blood gas tensions, pH, Hb, and oxygen saturation together with regional CBF were measured periodically. Hemorrhagic hypotension produced a mean decrease in arterial blood pressure of 27 +/- 4, 23 +/- 2, and 41 +/- 4% in the three groups, respectively, whereas reinfusion of the lamb's blood resulted in a return to control blood pressure within 3% in all three groups. In the pre-term fetal lamb, CBF decreased significantly in all regions during hypotension. In the near-term fetal lamb, only blood flow to the cortex decreased significantly during hypotension. In the newborn lamb, only the choroid plexus demonstrated a significant decrease in blood flow during hypotension. The lower limit of regional CBF autoregulation was identical to the resting mean arterial pressure in fetal life but significantly lower in newborn lambs. These experiments demonstrate for the first time that vulnerability to hypotension decreases with increasing maturity and that the brainstem, the phylogenetically oldest region of the brain, is the least vulnerable to the effects of hypotension at any age in the lamb model.     

Effect of indomethacin on cerebral blood flow velocity of premature newborns

Using the Doppler technique, the effect of therapeutic doses of indomethacin on the cerebral blood flow velocity (CBFV) of anterior cerebral arteries was studied in 13 preterm infants with patent ductus arteriosus. The first intravenous injection of indomethacin (0.2 mg/kg, group 1, n = 10) induced a significant decrease in the area under the velocity curve at 15 min (-22%), which was sustained until 120 min (-28%, p less than 0.005). In contrast, no significant change in CBFV occurred after the third dose (group 2, n = 7). In both groups, capillary blood gases, mean arterial blood pressure, and heart rate remained stable throughout the study. In 5 mechanically ventilated infants, the increase in CBFV secondary to suctioning was significantly attenuated after the first dose of indomethacin (p less than 0.02) but not after the third (p = 0.56). Thus, an initial dose of indomethacin may attenuate CBFV increases secondary to clinical manipulations in the preterm newborn.     

Haemodynamic responses and population pharmacokinetics of midazolam following administration to ventilated, preterm neonates

Objective: To evaluate the effects of intravenous midazolam on haemodynamic variables and cerebral blood flow velocity (CBFV) and to determine the pharmacokinetics using a population approach in very low birthweight (VLBW) ventilated infants.
Methodology: Physiological variables were measured at predetermined times in 10 infants with birthweight ≤1500 g following a bolus dose of intravenous midazolam (0.1 mg/kg). Heart rate, mean arterial blood pressure (MAP) and transcutaneous CO₂ (TcPCO₂) were recorded and CBFV was assessed by Doppler ultrasound. Midazolam concentrations were also measured and pharmacokinetic parameters determined using a population modelling package.
Results: No change in heart rate occurred during the study period, while the MAP decreased by 3 mmHg 5 min after midazolam administration compared to baseline values. A non-significant fall in TcPCO₂ was seen at 20 min. Mean CBFV decreased from the baseline by 12% at 5 min, then returning to predose values. Midazolam concentrations were in the range shown to be effective in sedation of paediatric intensive care infants with the elimination being delayed in comparison to older children.
Conclusions: As only minor cerebral and haemodynamic effects were found with the use of midazolam in stable ventilated preterm infants, it appears to be a safe, short-term sedative agent.     

Impaired early neurologic outcome in newborn piglets reoxygenated with 100% oxygen compared with room air after pneumothorax-induced asphyxia

Birth asphyxia is a serious problem worldwide, resulting in 1 million deaths and an equal number of neurologic sequelae annually. It is therefore important to develop new and better ways to treat asphyxia. In the present study we tested the effects of reoxygenation with room air or with 100% oxygen (O2) after experimental pneumothorax-induced asphyxia on the blood oxidative stress indicators, early neurologic outcome, and cerebral histopathology of newborn piglets. Twenty-six animals were studied in three experimental groups: 1) sham-operated animals (SHAM, n = 6), 2) animals reoxygenated with room air after pneumothorax (R21, n = 10), and 3) animals reoxygenated with 100% O2 after pneumothorax (R100, n = 10). In groups R21 and R100, asphyxia was induced under anesthesia with bilateral intrapleural room air insufflation. Gasping, bradyarrhythmia, arterial hypotension, hypoxemia, hypercarbia, and combined acidosis occurred 62 +/- 6 min (R21) or 65 +/- 7 min (R100; mean +/- SD) after the start of the experiments; then pneumothorax was relieved, and a 10-min reoxygenation period was started with mechanical ventilation with room air (R21) or with 100% O2 (R100). The newborn piglets then breathed room air spontaneously during the next 3 h. Blood oxidative stress indicators (oxidized and reduced glutathione, plasma Hb, and malondialdehyde concentrations) were measured at different stages of the experiments. Early neurologic outcome examinations (neurologic score of 20 indicates normal, 5 indicates brain-dead) were performed at the end of the study. The brains were next fixed, and various regions were stained for cerebral histopathology. In the SHAM group, the blood gas and acid-base status differed significantly from those measured in groups R21 and R100. In group R100, arterial PO2 was significantly higher after 5 (13.8 +/- 5.6 kPa) and 10 min (13.2 +/- 6.3 kPa) of reoxygenation than in group R21 (8.7 +/- 2.8 kPa and 9.2 +/- 3.1 kPa). The levels of all oxidative stress indicators remained unchanged in the study groups (SHAM, R21, and R100). The neurologic examination score in the SHAM group was 18 +/- 0, in group R21 it was 13.5 +/- 3.1, and in group R100 it was 9.5 +/- 4.1 (significant differences between SHAM and R21 or R100, and between R21 and R100). Cerebral histopathology revealed marked damage of similar severity in both asphyxiated groups. We conclude that the blood oxidative stress indicators and cerebral histopathology did not differ significantly after a 10-min period of reoxygenation with room air or with 100% O2 after pneumothorax-induced asphyxia, but reoxygenation with 100% O2 might impair the early neurologic outcome of newborn piglets.     

Dynamic cerebral autoregulation in sick newborn infants

The sick newborn infant is vulnerable to brain injury and impaired cerebral autoregulation is thought to contribute to this. Coherent averaging is a method of measuring the dynamic cerebral autoregulatory response that is particularly suitable for neonates. We used this method in combination with a measure of the gradient of the cerebral blood flow velocity (CBFV) response following transient blood pressure (BP) peaks to study dynamic autoregulation in infants undergoing intensive care. Term and preterm infants at high risk of neurologic injury were compared with a control group of infants, also undergoing intensive care. Simultaneous video-EEG, CBFV (using transcranial Doppler), and arterial blood pressure measurements were obtained intermittently during a study period of at least 2 h. Cerebral autoregulatory response curves were constructed for high risk and control groups. Intact cerebral autoregulation produces a characteristic response consisting of a brief period when CBFV follows arterial blood pressure but quickly returns to baseline value. An impaired autoregulatory response shows CBFV mirroring the arterial blood pressure curve closely. Thirteen high-risk infants, who also had seizures (10 term and 3 preterm) and 12 control infants (6 term and 6 preterm) were studied. Autoregulation was absent in high-risk term and preterm infants. It was also absent in preterm control infants. Term, neurologically healthy infants undergoing intensive care have an intact autoregulatory response. The constant passive response seen in high-risk infants may reflect the severity of the underlying neurologic disease.     

The effect of an increase in systemic arterial pressure in the newborn with right ventricular hypertension

To evaluate the effect of an elevation in systemic arterial pressure upon pulmonary blood flow and arterial oxygenation during right ventricular hypertension (RVH), we acutely studied 13 1-d-old piglets. Catheters were positioned in the pulmonary artery, both atria, and the aorta for hemodynamic measurements. An electromagnetic probe was positioned in the main pulmonary artery for pulmonary blood flow measurement. Systemic and regional blood flow were measured with the radiolabeled microsphere technique. A balloon-mounted catheter was advanced in the aorta and maintained at the lower thoracic level. After induction of RVH (pulmonary artery banding), a significant decrease in arterial O2 pressure from 54.4 +/- 1.6 to 10.6 +/- 0.4 kPa (p less than 0.01), a 30% reduction in systemic arterial pressure, and a 44% decrease in pulmonary blood flow were observed. During RVH, partial inflation of the aortic balloon to restore the systemic arterial pressure to its initial value led to an increase in arterial O2 pressure to 23.5 +/- 3.1 kPa (p less than 0.01). Full inflation of the balloon further increased the arterial O2 pressure to 32.6 +/- 2.9 kPa (p less than 0.01). Aortic balloon inflation increased pulmonary blood flow in 11 and systemic O2 delivery in nine of the 13 animals. RVH was associated with a significant increase in cerebral and right ventricular myocardial free-wall blood flow and a decrease in renal and bowel blood flow and O2 delivery (p less than 0.01). Aortic balloon inflation during RVH did not change either the cerebral or myocardial free-wall blood flow, but further significantly decreased renal and bowel blood flow and O2 delivery.(ABSTRACT TRUNCATED AT 250 WORDS)     

Autonomic adjustments to severe hypotension in fetal and neonatal sheep

In fetal sheep, severe hypotension causes heart rate (HR) slowing. Studies during development have also shown that a reflex bradycardia and hypotension can be elicited after chemostimulation with veratridine and is dependent on the age of the animal. In adults, a vagally mediated depressor reflex characterized by bradycardia, hypotension, and withdrawal of efferent sympathetic activity can be observed after stimulation of chemosensitive or mechanosensitive cardiac receptors with veratridine or in circumstances of reduced cardiac filling. This reflex, known as the Bezold-Jarisch reflex, plays a role in disease states such as myocardial ischemia and hemorrhage. The objectives of our study were to determine whether a sympathoinhibitor depressor reflex, along with the bradycardia, is observed during pharmacologically induced hypotension in fetal and newborn lambs. In both fetal and newborn lambs, HR and renal sympathetic nerve activity (RSNA) initially increased (p < 0.05) in response to nitroprusside infusion to reach a maximum value. The range (or "plateau") of mean arterial blood pressure over which maximum RSNA was maintained constant before withdrawal of sympathetic tone started to be observed was significantly (p < 0.05) smaller in fetuses (0.3 +/- 0.3 mm Hg) than newborn (6 +/- 1 mm Hg) lambs. Similarly, the plateau over which maximum HR was maintained before onset of bradycardia was significantly smaller in fetuses (4 +/- 1 versus 11 +/- 2 mm Hg). The mean arterial blood pressure level ("threshold") at which a depressor reflex was triggered was significantly (p < 0.05) lower in fetal than newborn sheep (35 +/- 2 versus 53 +/- 3 mm Hg for HR and 35 +/- 2 versus 57 +/- 2 mm Hg for RSNA). The rates of fall (slopes) for both HR and RSNA were also significantly (p < 0.05) more pronounced in fetuses (1.85 +/- 0.27 and 6.08 +/- 2.45%/mm Hg) than in newborns (1.21 +/- 0.16 and 1.97 +/- 0.32%/mm Hg). Bilateral vagotomy significantly increased the plateau of mean arterial blood pressure over which maximum RSNA and HR were maintained constant. Vagotomy also decreased the threshold for both RSNA and HR and the slope of the RSNA response to the nitroprusside infusion in newborn lambs. Results from this study show that activation of the arterial baroreflex during nitroprusside-induced hypotension is followed by withdrawal of sympathetic tone and bradycardia and that this depressor reflex is more pronounced in late-gestation fetuses than newborn lambs and is significantly attenuated after bilateral vagotomy in newborn lambs.     

Instillation rate effects of Exosurf on cerebral and cardiovascular haemodynamics in preterm neonates.

The acute effects of surfactant instillation rate on the cerebral and cardiovascular haemodynamics were studied in a randomised trial of 27 preterm neonates with respiratory distress syndrome (RDS). Cerebral blood flow velocity (CBFV), mean arterial blood pressure (MABP), blood gases and electroencephalogram (EEG) were continuously recorded before, during, and for at least 10 minutes after the administration of surfactant. The measurements were repeated one, three, and six hours later. Left ventricular output (LVO) and ductal patency were assessed 10 minutes before and then one, three, and six hours after surfactant administration. Surfactant (Exosurf) was instilled rapidly over five minutes in 13 infants and slowly over 15 minutes in 14 infants. The rapid group showed a significant but transient increase (mean 38%) in CBFV, a rise strongly related to an increase in carbon dioxide tension. No significant change in CBFV was observed in the slow group. There were no significant changes in EEG, MABP, LVO, or ductal shunting in either group. The findings suggest that rapid instillation of Exosurf leads to an increase in CBFV and partial carbon dioxide pressure (PCO2) and requires a close monitoring of blood gases to maintain adequate ventilation. Furthermore, the findings should alert clinicians to the need for slow infusion of Exosurf.     

Nebulization of sodium nitroprusside in lung-lavaged newborn piglets

The aim of the present study was to test the hypothesis that nebulization of the nitric oxide donor sodium nitroprusside may selectively reduce pulmonary vascular resistance and improve oxygenation in lung-lavaged newborn piglets. Thirteen anesthetized piglets (1-3 d old) were subjected to repeated lung lavages and then randomly assigned to one of the following two groups: 1) an SNP group, which received SNP nebulization, and 2) a saline group, which received saline nebulization. Pulmonary arterial pressure and pulmonary vascular resistance increased significantly after lung lavage, whereas cardiac output decreased significantly in both groups. After SNP nebulization, pulmonary arterial pressure decreased from 32+/-1 to 17+/-1 mm Hg (p < 0.01) and PVR decreased from 255+/-20 to 172+/-15 mm Hg L(-1) min(-1) kg(-1) (p < 0.01). The arterial tension of oxygen concomitantly increased from 9.4+/-4.0 to 17.0+/-3.0 kPa (p < 0.01), and the arterial/alveolar ratio of oxygen tension increased from 0.11+/-0.01 to 0.22+/-0.03 (p < 0.01). Systemic hemodynamics were not modified significantly during nebulization of SNP. On the other hand, all variables were stable during nebulization of saline. These data suggest that SNP nebulization produces a selective pulmonary vasodilatation and improves oxygenation in lung-lavaged newborn piglets.     

The effect of arterial PCO2-variations on ocular and cerebral blood flow in the newborn piglet

The response of ocular and cerebral blood flow to different arterial PCO2 levels was studied in ventilated paralyzed newborn piglets with the radionuclide-labeled 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.