Future directions in cardiocerebral resuscitation

Outcomes from pediatric cardiac arrest and cardiopulmonary resuscitation (CPR) seem to be incrementally improving. The past 2 decades have brought advances in the understanding of the pathophysiology of cardiac arrest and ventricular fibrillation, better treatment strategies, and a more robust standard for CPR epidemiology and research reporting. The evolution of practice based on an improved understanding of the pathophysiology and timing, intensity, duration, and variability of the hypoxic-ischemic insult should lead to goal-directed therapy gated to the phase of cardiac arrest and the postarrest period encountered. By strategically focusing therapies to specific phases of cardiac arrest and resuscitation and to the evolving pathophysiology and by implementing evidence-based practice, there is great promise that critical care interventions can lead the way to more successful cardiopulmonary and cerebral resuscitation in children.     

Basic and advanced paediatric cardiopulmonary resuscitation - guidelines of the Australian and New Zealand Resuscitation Councils 2010

Guidelines for basic and advanced paediatric cardiopulmonary resuscitation (CPR) have been revised by Australian and New Zealand Resuscitation Councils. Changes encourage CPR out-of-hospital and aim to improve the quality of CPR in-hospital. Features of basic CPR include: omission of abdominal thrusts for foreign body airway obstruction; commencement with chest compression followed by ventilation in a ratio of 30:2 or compression-only CPR if the rescuer is unwilling/unable to give expired-air breathing when the victim is 'unresponsive and not breathing normally'. Use of automated external defibrillators is encouraged. Features of advanced CPR include: prevention of cardiac arrest by rapid response systems; restriction of pulse palpation to 10 s to diagnosis cardiac arrest; affirmation of 15:2 compression-ventilation ratio for children and for infants other than newly born; initial bag-mask ventilation before tracheal intubation; a single direct current shock of 4 J/kg for ventricular fibrillation (VF) and pulseless ventricular tachycardia followed by immediate resumption of CPR for 2 min without analysis of cardiac rhythm and avoidance of unnecessary interruption of continuous external cardiac compressions. Monitoring of exhaled carbon dioxide is recommended to detect non-tracheal intubation, assess quality of CPR, and to help match ventilation to reduced cardiac output. The intraosseous route is recommended if immediate intravenous access is impossible. Amiodarone is strongly favoured over lignocaine for refractory VF and adrenaline over atropine for severe bradycardia, asystole and pulseless electrical activity. Family presence at resuscitation is encouraged. Therapeutic hypothermia is acceptable after resuscitation to improve neurological outcome. Extracorporeal circulatory support for in-hospital cardiac arrest may be used in equipped centres.     

Evaporative cooling as an adjunct to ice bag use after resuscitation from heat-induced arrest in a primate model

Heat stroke and other hyperthermia-related crises are serious clinical problems in childhood and adolescence. Rapid cooling is required to reduce morbidity and mortality. A variety of effective cooling methods exist, and some may interfere with monitoring and resuscitation or are not readily available. We studied in 12 pigtail monkeys the pathophysiology of immersion hyperthermia (42 degrees C) to cardiac arrest (1 min no flow) and CPR plus cooling to normothermia for restoration and stabilization of spontaneous normotension. This was followed by intractable shock and secondary arrest. These studies gave us the opportunity to compare two simple cooling methods applied during and after CPR: group I (n = 6) received application of ice bags to the groins, axillae, and neck. Group II (n = 6) received ice bags plus cold water wetting (sponging) over the entire anterior surface of trunk and extremities, plus fanning. CPR restored spontaneous circulation in four of six in each group, after CPR of 1.5-16 min (NS between groups). Speed of cooling correlated with speed of stabilization of spontaneous normotension. After cardiac arrest and during and after CPR, rectal temperature had declined from a lethal level of 42.2 degrees C to a safe level of 38.5 degrees C within 45 +/- 6 (38-53) min in group I, and within 28 +/- 4 (23-32) min in group II (p less than 0.05). Epidural and esophageal temperatures declined more rapidly than rectal temperature. For critical hyperthermia, we recommend immediate application of ice bags, cold water wetting (sponging), fanning, and head cooling combined when invasive blood cooling (the most effective method) is not immediately available.     

Blood flow during cardiopulmonary resuscitation with simultaneous compression and ventilation in infant pigs

We determined whether the simultaneous chest compression and ventilation (SCV) technique of cardiopulmonary resuscitation (CPR) enhances cerebral (CBF) and myocardial (MBF) blood flows and cerebral O2 uptake in an infant swine model of CPR as it does in most adult animal CPR models. We also tested whether SCV-CPR sustains CBF and MBF for prolonged periods of CPR when these flows ordinarily deteriorate. CPR was performed in two groups (n = 8) of pentobarbital anesthetized piglets (3.5-5.5 kg) with continuous epinephrine infusion (10 micrograms/kg/min). Conventional CPR was performed at 100 compressions/min, 60% duty cycle, 1:5 breath to compression ratio and 25-30 mm Hg peak airway pressure. SCV-CPR was performed at 60 compressions/min, 60% duty cycle and 60 mm Hg peak airway pressure applied during each chest compression. Peak right atrial and aortic pressures in excess of 80 mm Hg were generated during CPR in both groups. At 5 min of conventional and SCV-CPR, MBF was 38 +/- 7 and 46 +/- 7 mL.min-1.100 g-1 (+/- SE), respectively, and CBF was 15 +/- 3 and 13 +/- 2 mL.min1. 100 g-1, respectively. However, as CPR was prolonged to 50 min, the sternum progressively lost its recoil and the chest became more deformed. Lung inflation at high airway pressure with SCV-CPR did not prevent this chest deformation. Aortic pressure gradually declined, whereas right atrial and intracranial pressure remained constant in both groups. Consequently, MBF and CBF fell less than 10 mL.min-1.100 g-1 and cerebral O2 uptake was markedly impaired during prolonged conventional and SCV-CPR.(ABSTRACT TRUNCATED AT 250 WORDS)     

Influence of thromboxane A2 receptor antagonism on pulmonary vasoconstrictor responses

Thromboxane A2 (TxA2) is an arachidonic acid metabolite which causes severe pulmonary vasoconstriction (PV) and may mediate the PV produced by platelet-activating factor (PAF-acether) and leukotriene D4 (LTD4). To determine the role of TxA2 receptors on PAF-acether, LTD4, and hypoxia-induced PV, we administered PAF-acether 0.1 nmol/kg, the TxA2 analog U-46619 0.2 micrograms/kg/min, LTD4 3.0 micrograms/kg, or acute hypoxia (FiO2 = 0.12 for 3 min) before and during the infusion of the selective TxA2 receptor blocker SQ 29,548 50 micrograms/kg/min or vehicle into 27 open-chest, anesthetized newborn piglets, measuring pulmonary and systemic arterial pressures, cardiac index, and right and left ventricular pressures and dimensions. Mean pulmonary arterial pressure rose and cardiac index fell in response to PAF-acether (14 +/- 1 to 32 +/- 2 mm Hg and 91 +/- 5 to 15 +/- 5 mL/kg/min, both p less than 0.01), U-46619 (11 +/- 1 to 28 +/- 2 mm Hg and 93 +/- 10 to 36 +/- 9 mL/kg/min, both p less than 0.01), and LTD4 (13 +/- 3 to 22 +/- 2 mm Hg and 85 +/- 12 to 29 +/- 9 mL/kg/min, both p less than 0.05). Acute hypoxia increased PAP (12 +/- 1 to 26 +/- 2 mm Hg, p less than 0.01) but did not alter cardiac index. Infusion of SQ 29,548 prevented PAF-acether and U-46619-induced increases in pulmonary arterial pressure (13 +/- 1 to 14 +/- 1 mm Hg and 12 +/- 1 to 12 +/- 1 mm Hg) and decreases in cardiac index (70 +/- 4 to 70 +/- 3 mL/kg/min and 94 +/- 14 to 92 +/- 12 mL/kg/min) but failed to alter the response to LTD4 or hypoxia. Vehicle had no effect. We conclude that TxA2 receptors are not involved in LTD4 or hypoxia-induced PV but play an important role in the PV produced by PAF-acether and U-46619.     

Acetylcholine-induced coronary vasoconstriction and negative inotropy in the neonatal pig heart.

We investigated the influence of exogenously administered acetylcholine, nitric oxide, ADP, ATP, bradykinin, and substance P on coronary vascular tone in isolated, neonatal pig hearts (less than or equal to 4 d). Paced (180 bpm), isovolumically beating hearts underwent retrograde aortic perfusion, with an erythrocyte-enriched solution (hematocrit 0.15-0.20) at constant coronary flow (approximately 2.5 mL/min/g) corresponding to a perfusion pressure of approximately 60 mm Hg. Agonists were injected into the aortic root, and the peak change in coronary perfusion pressure from baseline and left ventricular pressure development were assessed. Nitric oxide (3 microL), ADP (30 nmol), ATP (30 nmol), bradykinin (125 ng), and substance P (50 ng) decreased the perfusion pressure (vasodilation) by 16.9 +/- 1.2, 25.3 +/- 4.4, 18.3 +/- 1.2, 18.9 +/- 1.4, and 7.1 +/- 1.6 mm Hg, respectively. Acetylcholine (0.5 and 1.0 nmol) produced a modest decrease in perfusion pressure (vasodilatation) of 4.2 +/- 0.8 and 3.8 +/- 0.5 mm Hg, respectively, whereas acetylcholine (5, 20, and 100 nmol) increased the perfusion pressure (vasoconstriction) by 16.7 +/- 2.7, 48.2 +/- 8.2, and 85.3 +/- 15.1 mm Hg, respectively. Acetylcholine also decreased left ventricular peak systolic pressure from 108.7 +/- 5.0 to 69.2 +/- 4.6, 56.3 +/- 6.1, and 48.2 +/- 6.4 mm Hg, for the 5, 20, and 100 nmol doses, respectively. Responses to acetylcholine were abolished by atropine (50 nmol). In a separate group of hearts, indomethacin (10(-6) M) reduced the peak change in perfusion pressure for the 5, 20, and 100 nmol doses of acetylcholine by 87%, 66%, and 48%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Evaluation of insulin sensitivity in obese offspring of diabetic rats by hyperinsulinemic-euglycemic clamp technique

Young adult macrosomic offspring of streptozotocin-induced mildly hyperglycemic rats exhibit accelerated growth through the first 10 wk of age. At 10 wk, oral glucose loading resulted in elevated plasma insulin and glucose concentrations compared to controls. To assess the mechanism of the abnormal glucose tolerance in vivo, hyperinsulinemic-euglycemic clamp studies were performed. Ten-wk-old rats were fasted overnight, and porcine insulin was infused (2.4 mU.kg-1.min-1). Glucose was infused concurrently at varying rates to maintain euglycemia for 40-60 min. Insulin levels were raised from a baseline value of 163 +/- 57 pmol/L (23 +/- 8 microU/mL) (SD) to 476 +/- 57 pmol/L (67 +/- 8 microU/mL) at steady state for males and from 178 +/- 43 pmol/L (25 +/- 6 microU/mL) to 454 +/- 43 pmol/L (64 +/- 6 microU/mL) for females. The results showed that the macrosomic male and female animals were significantly less sensitive to the effects of insulin than were their respective controls; this was evident by a lower increment in glucose disposal rate per unit increase in insulin (0.04 +/- 0.01 versus 0.11 +/- 0.03 for males and 0.05 +/- 0.03 versus 0.18 +/- 0.07 mg.kg-1 per microU/mL for females). The endogenous glucose production by the liver in the basal (fasted) state in the macrosomic group compared to controls was higher, suggesting possible hepatic insulin resistance. However, endogenous glucose production was suppressed to the same degree between the experimental and control groups during the hyperinsulinemic period, suggesting that the hepatic insulin resistance can be overcome by high insulin levels.(ABSTRACT TRUNCATED AT 250 WORDS)     

Endotoxin and hypoxia-induced intestinal necrosis in rats: the role of platelet activating factor.

We have previously shown that intravascular platelet activating factor (PAF) causes ischemic bowel necrosis in rats morphologically similar to neonatal necrotizing enterocolitis (NEC). Because endotoxin (LPS) and hypoxia are risk factors for NEC, we studied their effect on PAF metabolism and the development of intestinal injury. Young male Sprague-Dawley rats were anesthetized with pentobarbital and divided into six experimental groups: 1) control, 2) LPS alone (2 mg/kg), 3) hypoxia alone (5% O2), 4) LPS+hypoxia, 5) WEB 2086 (PAF antagonist)+LPS+hypoxia, and 6) SRI 63-441 (PAF antagonist)+LPS+hypoxia. Evaluations included blood pressure recording, superior mesenteric artery blood flow, arterial blood gas, white blood cell count, hematocrit, plasma PAF, plasma acetylhydrolase, plasma tumor necrosis factor, intestinal perfusion, and intestinal injury at 3 h. We found that LPS+hypoxia synergistically contributed to hypotension (mean blood pressure 27 +/- 5.6% baseline versus 101 +/- 3.9% control), metabolic acidosis (pH 7.05, base deficit 24 mEq/L), hemoconcentration, decreased superior mesenteric artery blood flow (2.2 +/- 0.3 mL/min versus 5.8 +/- 0.2 mL/min control), and intestinal injury. The morbidities resulting from LPS+hypoxia were partially or completely prevented by PAF antagonists. In addition, animals treated with LPS+hypoxia had neutropenia, elevated plasma acetylhydrolase, and elevated plasma TNF. These results suggest that endogenous PAF may contribute to LPS+hypoxia-induced intestinal hypoperfusion and necrosis.     

The effect of Escherichia coli endotoxin infusion on the ventilatory response to hypoxia in unanesthetized newborn piglets

To determine the effects of endotoxemia on the neonatal ventilatory response to hypoxia, 17 chronically instrumented and unanesthetized newborn piglets (相似文献   

Pediatric Cardiopulmonary Resuscitation and Stabilization

Cardiopulmonary arrest refers to cessation of clinically detectable cardiac activity. In children, it usually results from progression of shock, respiratory failure or cardiac dysrhythmia. Early recognition and timely interventions in above group of patients is the key to prevent progression to cardiac arrest. The goal of resuscitation is to urgently re-establish oxygenation of vital organs by attention to Airway, Breathing and Circulation. Measures to restore airway patency include positioning, suctioning, continuous positive airway pressure, relieving a foreign-body airway obstruction and, endotracheal intubation, tracheotomy or laryngeal mask airway. Breathing is supported with O₂ and if needed, bag-mask ventilation, or endotracheal intubation and ventilation. Patients with absent or feeble central pulse are given cardiac compressions (CPR) at a rate of 100/ min synchronized with ventilation. In sudden witnessed collapse, immediate defibrillation is warranted, followed by CPR and administration of drugs. In unwitnessed collapse, CPR is performed for five cycles or 2 min before defibrillation. In patients with shock, a venous or an intraosseous access is rapidly established to administer 20 ml/kg saline bolus. Supraventricular tachycardia is treated with vagal maneuvers and adenosine, if the patient is stable and with synchronized cardioversion, if unstable. Ventricular tachycardia is treated with amiodarone or lidocaine, if stable, and cardioversion if unstable or if drugs fail. Ventricular fibrillation needs defibrillation. Aggressive supportive care is needed during the post-resuscitation phase. There is no definite marker to determine futility of CPR. Short duration of arrest, early initiation of CPR, hypothermia as the cause of arrest, and in-hospital arrest have better prognosis.     

Cardiac hypertrophy and altered hemodynamic adaptation in growth-restricted preterm infants

The objective was to elucidate hemodynamic adaptation in very low birth weight (<1500 g) infants after intrauterine growth retardation. 31 growth-retarded (SGA, birth weight <-2 SD) and 32 appropriate for gestational age (AGA, birth weight within +/- 1 SD range) infants were enrolled. In SGA infants, the diastolic diameters of the interventricular septum and the left ventricle were increased, and serum brain natriuretic peptide (BNP) was elevated. Left ventricular output (LVO) of the AGA infants increased from 150 +/- 28 to 283 +/- 82 mL/kg/min during the study (p < 0.01). The SGA infants had a higher initial LVO than the AGA infants (243 +/- 47 versus 150 +/- 28 mL/kg/min, p < 0.05), but did not show further LVO increase during the study period. Red cell (RCV) and blood (BV) volume were assessed by Hb subtype analysis, when packed donor red cells were transfused. RCV and BV did not differ between the groups initially, but RCV increased by 18% and BV by 29% in the AGA group during the first 3 d. On day 3, AGA infants had larger BV than the SGA infants (88 +/- 5 versus 73 +/- 12 mL/kg, p < 0.05). In conclusion, cardiac hypertrophy, elevated initial LVO and BNP of the SGA infants suggest increased cardiac workload after intrauterine growth retardation. Based on the BV and RCV data, blood volume regulation may also be impaired. The data suggest that SGA preterm infants may be exposed to an increased risk of circulatory failure during early adaptation.     

Effects of pentoxifylline on the cardiovascular manifestations of group B streptococcal sepsis in the piglet.

Pentoxifylline (PTXF) is a methylxanthine that modifies leukocyte function and inhibits cytokine release. To evaluate its effects on the cardiovascular manifestations of sepsis secondary to group B streptococci, 14 anesthetized, mechanically ventilated piglets were studied over a 240-min period. Animals were randomly assigned to a treatment group that received a PTXF bolus (20 mg/kg) followed by a continuous infusion of 5 mg/kg/h before and during group B streptococci (1 x 10(8) colony forming units/kg/min) administration and a control group that received saline as a placebo. Comparison of the hemodynamic measurements and arterial blood gases during the first 90 min of PTXF treatment with those of the control group resulted in the following 90 min values: systemic arterial blood pressure was significantly higher in the PTXF group (89 +/- 10 versus 56 +/- 30 mm Hg; p less than 0.005) as was cardiac output (0.18 +/- 0.04 versus 0.10 +/- 0.07 L/kg/min; p less than 0.005). Pulmonary vascular resistance remained lower in the PTXF-treated animals (135 +/- 117 versus 248 +/- 119 mm Hg/L/min/kg; p less than 0.001), and these animals were less acidotic as measured by pH (7.07 +/- 0.2 versus 7.31 +/- 0.1; p less than 0.05) and base deficit (-15 +/- 9 versus -5 +/- 2 mmol/L; p less than 0.05). Median survival time was significantly longer in the PTXF group (210 versus 90 min; p less than 0.002). These data demonstrate that PTXF can ameliorate some of the deleterious hemodynamic manifestations of group B streptococci sepsis and result in improved survival in a young animal model.     

Increased cardiomyocyte intracellular calcium during endotoxin-induced cardiac dysfunction in guinea pigs

Septic shock is a complex pathophysiologic state characterized by circulatory insufficiency, multiple system organ dysfunction, and frequent mortality. Although profound cardiac dysfunction occurs during sepsis, the pathogenesis of this dysfunction remains poorly understood. To determine whether abnormalities in intramyocyte calcium accumulation might contribute to the development of cardiac dysfunction, we measured myocyte intracellular calcium during peak cardiac dysfunction after an endotoxin challenge. Intraperitoneal administration of Escherichia coli lipopolysaccharide 4 mg/kg to adult guinea pigs resulted in significantly impaired cardiac performance (Langendorff preparation) 18 h after challenge compared with control. This included diminished left ventricular pressure development (56 +/- 7 versus 95 +/- 4 mm Hg, p < 0.05), maximal rate of left ventricular pressure rise (998 +/- 171 versus 1784 +/- 94 mm Hg/s, p < 0.05) and left ventricular pressure fall (1014 +/- 189 versus 1621 +/- 138 mm Hg/s, p < 0.05). Assay of intracellular calcium in fura-2AM-loaded cardiac myocytes demonstrated increased intracellular calcium concentration in myocytes obtained from lipopolysaccharide-challenged animals compared with controls (234 +/- 18 versus 151 +/- 6 nM, p < 0.05). Inhibition of calcium-release channel (ryanodine receptor) opening by administration of dantrolene prevented the increase in intracytoplasmic calcium (159 +/- 8 versus 234 +/- 18 nM, p < 0.05) and partially ameliorated systolic and diastolic ventricular dysfunction. These data indicate that abnormalities of intracellular calcium contribute to the development of endotoxin-induced myocardial dysfunction.     

The contractility and performance of the preterm left ventricle before and after early patent ductus arteriosus occlusion in surfactant-treated lambs

The influence of left-right ductal shunting on early hemodynamic responses, namely left ventricular performance, contractility, and systemic perfusion was evaluated in nine preterm lambs (120 days gestational age) treated with surfactant. Blood gases were maintained in the physiological range using mechanical ventilation; hemodynamic and blood flow measurements (radionuclide labeled microspheres) were obtained before and after occlusion of the patent ductus arteriosus with a catheter balloon. The mean left-right ductal shunt before occlusion (1.2 h postnatal age) was 59 +/- 11% SD. Left ventricular output was increased in all lambs with PDA (pre: 306 +/- 106 versus post: 155 +/- 31 ml/min/kg; p less than 0.001); effective systemic blood flow and organ blood flows did not change. The left ventricle end-diastolic volume was increased in all and decreased following ductal occlusion (pre: 2.0 +/- 0.4 versus post: 1.5 +/- 0.2 ml/kg; p less than 0.01). Cardiac rate, ejection fraction, and contractility (peak dP/dt) did not change. Right-left ductal shunting was not detected in six similarly treated lambs. Thus, during the 1st h of life the hemodynamic profile of preterm lambs with patent ductus arteriosus was characterized by large magnitude left-right shunt and a "high" cardiac output state sufficient to maintain unchanged systemic perfusion. The increased left ventricle output was accomplished by increasing end-diastolic volume (Frank-Starling mechanism), but left ventricle contractility remained unchanged. We speculate that the preterm left ventricle may be unable to sustain the high level of pump performance and contractility required to compensate for the ductal "steal" of systemic blood flow.     

Circulatory failure in children with left-to-right shunt in the framework of congenital heart defects: pathophysiology and therapeutic results

In children with large left-to-right shunts secondary to congenital heart defects the imbalance between the pulmonary and systemic perfusion may lead to circulatory congestion with clinical signs similar to those of heart failure. The circulatory function in this state was evaluated by using the invasive measurements performed during cardiac catheterisations in n = 64 young patients with ventricular septal defect (n = 56) or complete atrioventricular septal defect (n = 8) aging 0.1-23.7 years (median 1.1 years). The mean shunt ratio was Qp/Qs = 2.4 (range 1-8). With increasing shunt ratio the pulmonary perfusion raised (r = 0.84), but the systemic output dropped significantly (r = -0.77) while the total cardiac output (Qp + Qs) increased slightly not exceeding 141/min/m2. In infants, the systemic hypoperfusion affects the hemoglobin content: Hb = 14.9-1.01 x Qs, r = 0.63, p < 0.01. This may be due to the diminished oxygen extraction reserve of 46%. With dropping systemic output, the vascular resistance increases and the mean aortic pressure (MAP) remains normal. The actual pressure values layed near to the curve of the normal aortic pressure calculated as MAP = Qs x Rs. This pressure-flow-resistance diagram was used to interpret the effects of vasodilators established by 7 studies: ACE-Inhibitors, Hydralazine, and Na-Nitroprusside reduce the vascular resistance effectively but induce hypotension, because the systemic output fails to increase. In the chronic circulatory congestion secondary to a large intracardiac left-to-right shunt the pulmonary perfusion increases with the shunt ratio but the systemic output decreases and the total cardiac output is limited to a maximum of 141/min/m2. In this state vasodilators cause systemic hypotension thus offering no acceptable therapeutic option.     

Assessment of antioxidant reserves and oxidative stress in cerebrospinal fluid after severe traumatic brain injury in infants and children

Studies in experimental traumatic brain injury (TBI) support a key role for oxidative stress. The degree of oxidative injury in clinical TBI, however, remains to be defined. We assessed antioxidant defenses and oxidative stress in pediatric TBI by applying a comprehensive battery of assays to cerebrospinal fluid samples. Using a protocol approved by our institutional review board, 87 cerebrospinal fluid samples from 11 infants and children with severe TBI (Glasgow Coma Scale score < or = 8) and 8 controls were studied. Cerebrospinal fluid was drained as standard care after TBI. CSF was assessed on d 1, 2, and 5-7 after ventricular drain placement. Biochemical markers of oxidative stress included F(2)-isoprostane and protein sulfhydryl (detected by ELISA and fluorescence assay, respectively). Antioxidant defenses were measured by determination of total antioxidant reserve (via chemiluminescence assay), and ascorbate (via HPLC) and glutathione (via fluorescence assay) concentrations. Free radical production (ascorbate radical) was assessed by electron paramagnetic resonance spectroscopy. F(2)-isoprostane was markedly increased versus control, maximal on d 1 (93.8 +/- 30.8 pg/mL versus 7.6 +/- 5.1 pg/mL, p < 0.05). Total antioxidant reserve was reduced versus control. Reduction was maximal on d 5-7 (81.8 +/- 3.7 microM versus 178.9 +/- 2.2 microM, p < 0.05). Ascorbate was remarkably reduced (53.8 +/- 8 microM versus 163.8 +/- 21 microM on d 1, p < 0.05). Ascorbate depletion was likely associated with its free radical oxidation, as evidenced by electron paramagnetic resonance spectroscopy. Glutathione levels increased on d 1, then decreased versus control (0.19 +/- 0.05 microM versus 1.2 +/- 0.16 microM, p < 0.05). This is the first comprehensive study of antioxidant reserve and oxidative injury in clinical TBI. Progressive compromise of antioxidant defenses and evidence of free radical-mediated lipid peroxidation are noted. These markers could be used to monitor antioxidant strategies in clinical trials.     

Management of symptomatic Wolff–Parkinson–White syndrome in childhood

The term “ventricular preexcitation” or “preexcitation” refers to the presence of a delta wave and short PR interval on electrocardiogram (ECG) during normal sinus rhythm. The Wolff–Parkinson–White (WPW) syndrome refers to preexcitation during sinus rhythm, in association with episodes of supraventricular tachycardia (SVT). The delta wave represents extra-nodal conduction via an accessory connection located along the atrioventricular groove or the septal region, and this substrate can support atrioventricular reentrant tachycardia. Patients with Wolff–Parkinson–White syndrome may experience symptoms of palpitations, dizziness, syncope, or sudden cardiac arrest related to supraventricular tachycardia; infants may present with congestive heart failure. Catastrophic symptoms such as cardiac arrest or sudden death may be triggered from atrial fibrillation with rapid antegrade conduction to the ventricle via the accessory connection, resulting in ventricular fibrillation [1], [2], [3], [4]; this risk is likely higher in patients in the first three decades of life [4], [5]. Sudden cardiac arrest as the initial symptom may be more common in younger patients [2], [4], [6]; for this reason, appropriate evaluation and management of the young patient with preexcitation is essential.     

Transfer and metabolism of retinol by the perfused human placenta.

The transfer and metabolism of retinol by human placenta was investigated using an in vitro perfusion system with independent maternal and fetal circulations. 3H-retinol bound to albumin added to the maternal perfusate was rapidly taken up and concentrated by the placenta to levels 16.5 +/- 5.28 times the maternal perfusate. Approximately 8% of the retinol retained in the placenta was esterified. No metabolites were detected in the perfusates. Perfusion of placenta with retinol bound to retinol-binding protein (RBP) reduced the placental concentration to 4.4 +/- 1.72 times the maternal concentration and eliminated evidence of metabolism. The transfer rate of RBP:3H-retinol was less than that of albumin:14C-retinol when measured concurrently in three experiments (clearances 0.11 versus 0.75 mL/min, 0.21 versus 1.7 mL/min, and 0.29 versus 0.48 mL/min, respectively). Transfer of the radioactive retinol was more rapid than 125I-RBP or albumin, indicating that retinol was transferred independently of the proteins. The transfer index of retinol (clearance retinol:clearance L-glucose) was 0.73 +/- 0.085 compared to 2.1 +/- 0.36 for thiamin and 3.4 +/- 0.95 for riboflavin, both water-soluble vitamins with active transport systems. The retinol transferred to the fetal perfusate is not bound to RBP, as demonstrated by gel filtration chromatography and chromatography on a transthyretin affinity column, despite the availability of RBP in the cord serum added to the perfusate. The endogenous retinol in the cord serum is bound to RBP.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cardiovascular impact of dobutamine in neonates with myocardial dysfunction

OBJECTIVE: To study effects of dobutamine on cardiac functional parameters, cerebral, mesenteric and renal blood flow in preterm neonates with myocardial dysfunction. STUDY DESIGN: Prospective evaluation of Doppler sonographically measured left ventricular systolic time intervals, stroke volume (SV), cardiac output (CO), and blood flow parameters of anterior cerebral artery (ACA), superior mesenteric artery (SMA) and renal arteries (RA), before, after 20 min and 8-10 h of dobutamine treatment in 20 neonates (gestational age 29.6+/-4.4 weeks, birth weight 1450+/-609 g and postnatal age 2+/-2.1 days). Dobutamine was given in a mean dosage of 9.1+/-1.1 microg/kg. RESULTS: After 20 min SV increased from 1.71+/-0.5 ml to 2.12+0.57 ml/kg, CO from 223+/-76 to 290 ml/kg/min. A shortening of left ventricular pre ejection period from 86+/-12 to 66+/-13 ms and of the ratio of pre-ejection period/ejection time from 0.52+/-0.12 to 0.40+/-0.11 were observed. Blood flow velocities of ACA increased after 8-10 h: peak systolic flow velocity (PSV) from 19.0+/-6 to 29.6+/-7.1 ms, end diastolic velocity (EDV) from 2.9+/-2.6 to 12.7+/-11.3 ms. PSV of SMA increased from 32.5+/-4.7 to 49.7+/-7.8 ms after 8-10 h, EDV from 8.9+/-8 ms to 20.6+/-6.1 ms. PSV of RA increased from 18.2+/-6.1 ms to 39.9+/-4.8 ms, EDV from 2.2+/-1.2 to 8.2+/-2.1 ms after 8-10 h. The pulsatility indices decreased significantly after 8-10 h: ACA from 2.3+/-0.6 to 1.4+/-0.5, SMA from 1.7 to 1.2 and RA from 2.57 to 1.57. CONCLUSION: Dobutamine improves the cardiac functional parameters already after 20 min and has an influence on the blood flow parameters of ACA, SMA and RA 8-10 h after administration in neonates with myocardial dysfunction.     

雌二醇对幼兔未成熟心肌缺血-再灌注损伤的保护作用

目的　探讨雌二醇对幼兔心肌缺血一再灌注损伤的保护作用。方法　采用离体心脏Langendorff灌注模型。根据停搏液的不同 ,将 32只 3～ 4周龄雌性日本大耳白兔随机分为 4组 (n =8) :①对照组 (C组 ) ,单用StThomasII停搏液 ;②雌二醇组 (E2 组 ) ,StThomasII停搏液中加入 10 -6mol/L 17 β雌二醇 ;③雌二醇受体阻断剂组 (B组 ) ,StThomasII停搏液中加入 10 -6mol/L 17 β 雌二醇受体阻断剂 4 Hydroxy Tamoxifen ;④EB组 ,StThomasII停搏液中加入 10 -6mol/L 17 β 雌二醇和 4 Hydroxy Tamoxifen。心脏停跳 6 0min ,复灌后的不同时间点观察每组心功能各项指标的恢复率、心肌酶等生化指标及心肌超微结构的改变。结果　E2 组冠脉流出量的恢复率从复灌后 6 0min起、左室发展压和左室压最大变化速率的恢复率从复灌后 4 0min起均高于其他 3组 (P <0 .0 1或 0 .0 5 ) ,心肌超微结构改变则较其他 3组轻 ,心肌含水量、MDA含量及冠脉流出液心肌酶含量均低于其他 3组(P <0 .0 5 ) ,E2 组心肌组织ATP含量高于C组和B组 (P <0 .0 5 )。结论　雌二醇对幼兔缺血一再灌注损伤心肌有较好的保护作用 ,其保护作用为心肌细胞雌二醇受体介导。