Clara Kurishima

Resuscitation of Preterm Infants with Reduced Oxygen Results in Less Oxidative Stress than Resuscitation with 100% Oxygen

The objective of this study was to determine the effects of the level of inhaled oxygen during resuscitation on the levels of free radicals and anti-oxidative capacity in the heparinized venous blood of preterm infants. Forty four preterm infants <35 weeks of gestation with mild to moderate neonatal asphyxia were randomized into two groups. The first group of infants were resuscitated with 100% oxygen (100% O2 group), while in the other group (reduced O2 group), the oxygen concentration was titrated according to pulse oximeter readings. We measured total hydroperoxide (TH) and redox potential (RP) in the plasma within 60 min of birth. The integrated excessive oxygen (∑(FiO2-0.21) × Time(min)) was higher in the 100% O2 group than in the reduced O2 group (p<0.0001). TH was higher in the 100% O2 group than in the reduced O2 group (p<0.0001). RP was not different between the 100% O2 and reduced O2 groups (p = 0.399). RP/TH ratio was lower in the 100% O2 group than in the reduced O2 group (p<0.01). We conclude that in the resuscitation of preterm infants with mild to moderate asphyxia, oxidative stress can be reduced by lowering the inspired oxygen concentration using a pulse oximeter.

Aortic stiffness and aortic dilation in infants and children with tetralogy of Fallot before corrective surgery: evidence for intrinsically abnormal aortic mechanical property

OBJECTIVE The present study tested the hypothesis that there is an intrinsic abnormality of aortic elasticity in infants/children with tetralogy of Fallot (TOF) before corrective surgery. The study also determined the independent and quantitative effects of aortic volume load on aortic dilation in this group of TOF patients. METHODS Aortic stiffness (pulse wave velocity; PWV) and aortic volume load (aortic volume flow) were measured during catheterization in 37 infants and children with TOF before corrective surgery and in 55 control subjects. RESULTS PWV was significantly higher in TOF patients than in controls, irrespective of age, sex, hemodynamic burden on the aortic wall, and existence of aorto-pulmonary shunt. Aortic diameter was also significantly greater in TOF patients than in controls. Multivariate regression analysis identified aortic volume load as an independent determinant of aortic dilation (aortic diameter = 0.72 aortic flow + 26.1 body surface area + 2.79, r(2) = 0.58, p < 0.001). Increased aortic-wall stiffness correlated with the increase in aortic diameter in patients with dominant left-to-right shunt (without aortic volume load); aortic diameter = 0.007 PWV + 13.5 body surface area (BSA) + 6.3 (r(2) = 0.73, p < 0.05). CONCLUSIONS The present study highlighted the intrinsic abnormality of the mechanical property of the aortic wall as a feature of aortopathy in TOF. The study also indicated that aortic volume overload and, to a lesser extent, intrinsically high aortic stiffness correlated significantly with aortic dilation in TOF.

Hemodynamic performance of the Fontan circulation compared with a normal biventricular circulation: a computational model study

The physiological limitations of the Fontan circulation have been extensively addressed in the literature. Many studies emphasized the importance of pulmonary vascular resistance in determining cardiac output (CO) but gave little attention to other cardiovascular properties that may play considerable roles as well. The present study was aimed to systemically investigate the effects of various cardiovascular properties on clinically relevant hemodynamic variables (e.g., CO and central venous pressure). To this aim, a computational modeling method was employed. The constructed models provided a useful tool for quantifying the hemodynamic effects of any cardiovascular property of interest by varying the corresponding model parameters in model-based simulations. Herein, the Fontan circulation was studied compared with a normal biventricular circulation so as to highlight the unique characteristics of the Fontan circulation. Based on a series of numerical experiments, it was found that 1) pulmonary vascular resistance, ventricular diastolic function, and systemic vascular compliance play a major role, while heart rate, ventricular contractility, and systemic vascular resistance play a secondary role in the regulation of CO in the Fontan circulation; 2) CO is nonlinearly related to any single cardiovascular property, with their relationship being simultaneously influenced by other cardiovascular properties; and 3) the stability of central venous pressure is significantly reduced in the Fontan circulation. The findings suggest that the hemodynamic performance of the Fontan circulation is codetermined by various cardiovascular properties and hence a full understanding of patient-specific cardiovascular conditions is necessary to optimize the treatment of Fontan patients.

Cerebral Circulation in Patients With Fontan Circulation: Assessment by Carotid Arterial Wave Intensity and Stiffness

BACKGROUND Information about the cerebral circulation in the Fontan physiology is scarce. We tested our hypothesis that cerebral perfusion is impaired in the Fontan circulation by analyzing wavefront behavior (wave intensity) and assessing arterial stiffness at the carotid artery. METHODS The carotid arterial wave intensity and stiffness were computed in 34 consecutive Fontan patients (11.5±8.6 years) and 20 control subjects (13.4±6.0 years) using an echocardiographic vascular tracking system, which enabled simultaneous measurements of instantaneous carotid arterial pressure and flow velocity. RESULTS The carotid arterial blood flow was significantly lower in the Fontan patients than in the controls (p<0.05). Wave intensity analysis demonstrated a significant decrease in the compression and acceleration wave, an important forward traveling wave for cerebral circulation, in the Fontan patients compared with the control subjects (31.0±2.6 versus 48.1±4.4 mm Hg⋅m⋅s3⋅10(3); p=0.001). In addition, the negative wave intensity normalized to the first positive wave, representing a wave reflection from peripheral cerebral vessels, was significantly increased in the Fontan patients compared with that in control subjects. Carotid arterial stiffness and central venous pressure were also significantly increased in the Fontan patients and were independent determinants of the decreased first positive wave, suggesting the pathophysiologic importance of carotid arterial stiffness and central venous pressure as inflow and outflow resistance to the cerebral circulation, respectively, in the Fontan physiology. CONCLUSIONS These results suggest impaired cerebral perfusion caused by vascular stiffening and high central venous pressure in patients with Fontan circulation. Longitudinal studies examining the association between cerebral circulation and neurodevelopmental outcome after Fontan operation are warranted.

Changes in skin and subcutaneous perfusion in very-low-birth-weight infants during the transitional period.

Background: Conventional parameters of circulation that are routinely used in neonatal intensive care units, including blood pressure, have been reported to be inadequate in improving prognosis of very-low-birth-weight (VLBW) infants. Recently, the importance of evaluating the blood flow to each organ, including both vital and nonvital organs, has been increasingly recognized. Objectives: To study the changes in peripheral perfusion occurring in VLBW infants of less than 32 weeks’ gestation during the extrauterine transitional period. Methods: In 32 VLBW infants of less than 32 weeks’ gestation, forehead blood flow (FBF) and lower-limb blood flow (LBF) were measured for 48 h after birth using a novel laser Doppler flowmeter, and the indices of vascular resistance were estimated. Superior vena cava (SVC) blood flow was measured by echocardiography. Changes in these variables of circulation as well as the correlations were evaluated. Results: Both FBF and LBF significantly increased at 24 h, while the SVC flow remained unchanged over the same period. Both forehead and lower-limb vascular resistance indices significantly decreased at 24 h. LBF was negatively and positively correlated with estimated upper body vascular resistance and SVC flow, respectively. Conclusions: The increase in the peripheral blood flow along with the decrease in the peripheral vascular resistance indices, without an increase in the systemic blood flow at 24 h of age, indicated vasodilation in skin and subcutaneous tissue during the transitional period in VLBW infants. FBF and LBF can be useful parameters as indicators of both peripheral and systemic circulation.

Impaired Cerebral Perfusion After Bilateral Pulmonary Arterial Banding in Patients With Hypoplastic Left Heart Syndrome

BACKGROUND Recent studies have shown that bilateral pulmonary artery banding (bil-PAB) for hypoplastic left heart syndrome (HLHS) is not superior to the neonatal Norwood procedure in terms of overall mortality and neurodevelopmental outcome. We tested our hypothesis that bil-PAB is associated with negative hemodynamic effects on cerebral circulation. METHODS The acute effects of bil-PAB on cerebral circulation were assessed by serial measurements of cerebral Doppler flow velocities in 9 patients immediately after bil-PAB. To evaluate the chronic effects of bil-PAB on cerebral perfusion, the oxygen demand-supply balance between the lower and upper body, designated as oxygenation balance index (OBI), was calculated in another set of 13 patients using oxymetric data before stage II palliation. Data were compared with those of 13 patients who underwent the Norwood operation. RESULTS The preoperative cerebral blood flow velocities of the patients were at the lowest levels reported in healthy neonates. Bil-PAB did not increase cerebral blood flow in the first week after the procedure. OBI was significantly lower in patients treated with bil-PAB (p < 0.005) than in those treated with the Norwood procedure, indicating impaired cerebral perfusion after bil-PAB. Importantly, the OBI in the bil-PAB group, but not in the Norwood group, significantly decreased with time after the procedure. In addition, cerebral perfusion was more vulnerable to the changes in pulmonary and systemic blood flow in the bil-PAB group than in the Norwood group. CONCLUSIONS A hybrid approach followed by comprehensive stage II palliation may not be an optimal strategy for HLHS and should be evaluated further.

Cardiac biomarkers in children with congenital heart disease.

BackgroundMost congenital heart diseases (CHDs) have specific hemodynamics, including volume and pressure overload, as well as cyanosis and pulmonary hypertension, associated with anatomical abnormalities. Such hemodynamic abnormalities can cause activation of neurohormones, inflammatory cytokines, fibroblasts, and vascular endothelial cells, which in turn contribute to the development of pathologic conditions such as cardiac hypertrophy, fibrosis, and cardiac cell damages and death. Measuring biomarker levels facilitates the prediction of these pathological changes, and provides information about the stress placed on the myocardial cells, the severity of the damage, the responses of neurohumoral factors, and the remodeling of the ventricle. Compared to the ample information on cardiac biomarkers in adult heart diseases, data from children with CHD are still limited.Data sourcesWe reviewed cardiac biomarkers-specifically focusing on troponin as a biomarker of myocardial damage, amino-terminal procollagen type III peptide (PIIIP) as a biomarker of myocardial fibrosis and stromal remodeling, and B-type natriuretic peptide (BNP)/N-terminal proBNP as biomarkers of cardiac load and heart failure, by introducing relevant publications, including our own, on pediatric CHD patients as well as adults.ResultsLevels of highly sensitive troponin I are elevated in patients with atrial septal defects (ASDs) and ventricular septal defects (VSDs). PIIIP levels are also elevated in patients with ASD, VSD, pulmonary stenosis, and Tetralogy of Fallot. Measurement of BNP and N-terminal proBNP levels shows good correlation with heart failure score in children.ConclusionsIn the treatment of children with CHD requiring delicate care, it is vital to know the specific degree of myocardial damage and severity of heart failure. Cardiac biomarkers are useful tools for ascertaining the condition of CHDs with ease and are likely to be useful in determining the appropriate care of pediatric cardiology patients.

Arterial stiffness in patients after Kawasaki disease without coronary artery involvement: Assessment by performing brachial ankle pulse wave velocity and cardio-ankle vascular index

BACKGROUND It remains unclear whether systemic arterial beds other than the coronary arteries are truly healthy in patients without coronary artery lesions (CAL) after Kawasaki disease (KD). We tested the hypothesis that patients with KD without echocardiographic evidence of CAL during the acute phase of the disease have abnormal mechanical properties in systemic arteries later. METHODS AND RESULTS We studied 201 consecutive patients with KD (age 2-23 years, mean 10±4 years; 109 male, 92 female) without CAL during the acute phase. Data were compared with those in 129 control subjects (age 2-25 years, mean 10±4 years; 73 male, 56 female; control group). We examined arterial stiffness by using the brachial-ankle pulse wave velocity (baPWV) and the cardio-ankle vascular index (CAVI). The baPWV in the KD group was significantly higher than that in the control group (913±121cm/s vs. 886±135cm/s, p=0.04). In contrast, there was no significant difference in CAVI (4.0±1.0 vs. 4.2±1.0, p=0.9) between the two groups. Multivariate analysis indicated a highly significant difference in baPWV (higher baPWV in patients with KD than in controls, p=0.004), after controlling for age, gender, body height and weight, and systolic and diastolic blood pressure, but no difference in CAVI between the groups. CONCLUSION Years after KD occurs in patients without apparent CAL during the acute phase, there is a small but significant change in systemic arterial properties, characterized by increased wall stiffness. The clinical importance of these findings must be clarified by performing long-term follow-up studies.

Rare case of disseminated neonatal zygomycosis mimicking necrotizing enterocolitis with necrotizing fasciitis.

A set of monochorionic male twins presented with intestinal perforation. The smaller twin was diagnosed with necrotizing enterocolitis followed by sepsis, disseminated intravascular coagulation, and necrotizing fasciitis of the abdominal wall. The infant died on the fourth day after surgery, 16 days after birth. Surgical specimens and autopsy revealed a disseminated zygomycotic infection. Gastrointestinal zygomycosis followed by necrotizing fasciitis in premature infants is a rare condition and mimics necrotizing enterocolitis clinically. Necrotizing fasciitis after gastrointestinal zygomycosis in premature infants is considered a poor prognostic sign. Gastrointestinal zygomycosis should be considered in the differential diagnosis of necrotizing enterocolitis.

Levels of Catecholamines, Arginine Vasopressin and Atrial Natriuretic Peptide in Hypotensive Extremely Low Birth Weight Infants in the First 24 Hours after Birth

Background: Extremely low birth weight infants (ELBWI) often suffer from severe hypotension in the early neonatal period. However, few previous studies have ever revealed plasma levels of vasoactive substances which regulate the cardiovascular system in ELBWI. Objective: To study plasma levels of vasoactive substances in ELBWI with hypotension during the first 24 h of life. Methods: 22 ELBWI with hypotension (gestational age 26.4 ± 1.9 weeks; birth weight 751 ± 135 g) were involved in the study. After initial volume therapy, the infants were arbitrarily divided into two groups depending on requirement of dopamine dosage: severe hypotension group (SH; dopamine >10 μg/kg/min, n = 9) and mild hypotension group (MH; dopamine ≤10 μg/kg/min, n = 13). Plasma levels of dopamine, norepinephrine, epinephrine, arginine vasopressin, and atrial natriuretic peptide were measured at admission and at 24 h after birth. Results: Infants in the SH group had higher plasma dopamine than infants in the MH group both at admission (median; range: 14,410; 224–46,770 vs. 7,900; 32–21,220 pg/ml, p < 0.05) and at 24 h (80,920; 494–146,100 vs. 25,680; 10,130–63,180 pg/ml; p < 0.05). The norepinephrine/dopamine ratio (median; range) was lower in the SH group than in the MH group at admission (0.3; 0.0–1.0 vs. 1.1; 0.1–25.1; p < 0.01). Plasma levels of atrial natriuretic peptide or arginine vasopressin were not different between the two groups. Conclusions: ELBWI with SH may have decreased conversion of dopamine to norepinephrine. We speculate that this mechanism may contribute to development of SH in ELBWI.