Knockdown of Long Noncoding RNA SNHG14 Protects H9c2 Cells Against Hypoxia-induced Injury by Modulating miR-25-3p/KLF4 Axis in Vitro.

ABSTRACT: Cyanotic congenital heart disease (CCHD) is the main cause of death in infants worldwide. Long noncoding RNAs (lncRNAs) have been pointed to exert crucial roles in development of CHD. The current research is designed to illuminate the impact and potential mechanism of lncRNA SNHG14 in CCHD in vitro. The embryonic rat ventricular myocardial cells (H9c2 cells) were exposed to hypoxia to establish the model of CCHD in vitro. Quantitative real-time polymerase chain reaction was conducted to examine relative expressions of SNHG14, miR-25-3p, and KLF4. Cell viability was determined by the MTT assay. Lactate dehydrogenase (LDH) was measured by an LDH assay kit. Apoptosis-related proteins (Bax and Bcl-2) and KLF4 were detected by Western Blot. The targets of SNHG14 and miR-25-3p were verified by the dual-luciferase reporter assay. SNHG14 and KLF4 were upregulated, whereas miR-25-3p was downregulated in hypoxia-induced H9c2 cells and cardiac tissues of patients with CCHD compared with their controls. Knockdown of SNHG14 or overexpression of miR-25-3p facilitated cell viability, while depressing cell apoptosis and release of LDH in hypoxia-induced H9c2 cells. MiR-25-3p was a target of SNHG14 and inversely modulated by SNHG14. MiR-25-3p could directly target KLF4 and negatively regulate expression of KLF4. Repression of miR-25-3p or overexpression of KLF4 reversed the suppression impacts of sh-SNHG14 on cell apoptosis and release of LDH as well as the promotion impact of sh-SNHG14 on cell viability in hypoxia-induced H9c2 cells. Sh-SNHG14 protected H9c2 cells against hypoxia-induced injury by modulating miR-25-3p/KLF4 axis in vitro.

Does the prophylactic and therapeutic use of beta-blockers in preoperative patients with tetralogy of Fallot significantly prevent and treat the occurrence of cyanotic spells?

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was 'Does the use of beta-blockers significantly prevent and treat the occurrence of cyanotic spells in preoperative infants with tetralogy of Fallot?' Altogether, 80 papers were found using the reported search, of which 6 represented the best evidence to answer the clinical question. The author, journal, date, country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. The participants in the papers reviewed were uncorrected (native or palliated) tetralogy of Fallot patients, all younger than 18 years of age, with some patients younger than 1 year. Each study reviewed included at least 10 patients, and all the studies were case series. Although even the most recent studies found were from 30 years ago, their data remain relevant. Several reviews reported either cases of overdosage or changes in efficacy of treatment after long-term usage. Four of the 6 case reviews demonstrated a decrease in the number of recurring cyanotic spells in at least 66% of the participants, following the introduction of beta-blockers. We can therefore conclude that the use of beta-blockers prevents the occurrence of cyanotic spells in preoperative patients with tetralogy of Fallot. There were insufficient data to establish optimum dosages or duration of treatment.

Persistent pulmonary hypertension of the newborn.

Failure of the normal circulatory adaptation to extrauterine life results in persistent pulmonary hypertension of the newborn (PPHN). Although this condition is most often secondary to parenchymal lung disease or lung hypoplasia, it may also be idiopathic. PPHN is characterized by elevated pulmonary vascular resistance with resultant right-to-left shunting of blood and hypoxemia. Although the preliminary diagnosis of PPHN is often based on differential cyanosis and labile hypoxemia, the diagnosis is confirmed by echocardiography. Management strategies include optimal lung recruitment and use of surfactant in patients with parenchymal lung disease, maintaining optimal oxygenation and stable blood pressures, avoidance of respiratory and metabolic acidosis and alkalosis, and pulmonary vasodilator therapy. Extracorporeal membrane oxygenation is considered when medical management fails. Although mortality associated with PPHN has decreased significantly with improvements in medical care, there remains the potential risk for neurodevelopmental disability which warrants close follow-up of affected infants after discharge.

Neurally adjusted ventilatory assist for infants under prolonged ventilation.

BACKGROUND: Severe bronchopulmonary dysplasia often leads to prolonged mechanical ventilation lasting several months. Cyanotic episodes frequently occur in these patients, necessitating long-term sedation and/or intermittent muscle paralysis. Neurally adjusted ventilatory assist (NAVA) might provide precisely the amount of support that these patients need without sedation. METHODS: We reviewed the medical records of preterm infants who underwent tracheostomy and required mechanical ventilation for >6 months during a period of 6 years. We compared two groups of patients: those supported with NAVA for ≥2 months versus those supported by pneumatically triggered assist methods. We also evaluated any change after NAVA use in the NAVA group. RESULTS: Among 14 prematurely born patients who received prolonged ventilation, nine were supported with NAVA and five were supported using other ventilator modes. Duration of continuous sedation was significantly shorter and the bolus use of sedatives was also significantly lower in the NAVA group than in the pneumatically triggered assist group. In addition, the NAVA group received a lower dose of dexamethasone than the pneumatically triggered assist group. Compared with before NAVA, the frequency of cyanotic episodes and of the bolus sedatives was significantly decreased after implementation of NAVA. CONCLUSIONS: For infants on prolonged mechanical ventilation, NAVA could reduce cyanotic episodes and the need for sedatives and dexamethasone. NAVA may be superior to pneumatically triggered modes in terms of the minimization of patient-ventilator dyssynchrony while delivering appropriate respiratory support in premature infants with tracheostomy.

A case of severe methemoglobinemia caused by hair dye poisoning.

CONTEXT: Hair dyes are widely used and very popular xenobiotics. Most of these products contain paraphenylenediamine (PPD) that can cause methemoglobinemia. We here report a case of severe methemoglobinemia that we treated using large amounts of methylene blue. CASE DETAILS: A 30-year-old man visited a regional hospital with cyanosis. He was congenitally blind and had autism. For several weeks, he had mistaken hair dye for toothpaste. When he arrived at a regional hospital, he was drowsy with cyanosis and his initial serum methemoglobin (MetHb) level was 59.5%. After being treated with 2 mg/kg methylene blue (1 mg/kg × 2 administrations), he was transferred to a tertiary university hospital. Upon presentation at the Emergency Department in the tertiary hospital, his MetHb level was found to be 49.4% and his oxygen saturation was 80%. He was then admitted to the intensive care unit. After treatment with 4 mg/kg methylene blue (1 mg/kg × 4 administrations), he successfully recovered. DISCUSSION: Because PPD can result in serious methemoglobinemia, clinicians should test it in cyanotic patients who have been exposed to hair dye for an extended period.

[General anesthesia for a patient with Eisenmenger syndrome: a case report].

Generally, anesthesiologists believe that patients with Eisenmenger syndrome (ES) undergoing noncardiac surgery have significant risks of perioperative morbidity and mortality. Because of the recent strides in medical care, these patients often require anesthesia. We describe a case of a 45-year-old woman with ES and Down syndrome who underwent intraocular lens implantation under general anesthesia. She was refused general anesthesia for the surgery in other hospitals for more than 2 years. She had no adverse perioperative events, and was discharged the next day. Patients with ES have increased risks with general anesthesia for noncardiac surgery, but the risk of morbidity and mortality seems to be less than previously thought.

Conal septal morphometrics can identify higher risk neonates with tetralogy of Fallot.

BACKGROUND: Some neonates with tetralogy of Fallot (TOF) have rapid progression of right ventricular outflow tract obstruction, requiring early repair irrespective of Doppler gradient as measured in the neonatal period. The aim of this study was to test the hypothesis that infundibular morphology in neonates with TOF is associated with the occurrence of hypercyanotic spells and need for neonatal surgery. METHODS: Fifty patients with TOF undergoing surgical repair from 2003 to 2009 were studied. Neonatal echocardiograms were retrospectively analyzed to measure conal septal angle (the angle between the conal septum and the horizontal plane passing through the center of the aortic valve in the parasternal short-axis view, with a larger angle denoting more anterocephalad deviation of conal septum), conal septal thickness and length, the degree of aortic dextroposition, and sizes and Z scores of the pulmonary annulus and the main and branch pulmonary arteries. Outcomes included the occurrence of hypercyanotic spells and the need for neonatal surgery. RESULTS: The median age at first echocardiogram was 2 days (range, 0-12 days). The median age at surgery was 94 days (range, 5-282 days); hypercyanotic spells occurred in 17 patients (34%), and nine (18%) underwent neonatal repair. The presence of a wider conal septal angle was significantly associated with the occurrence of hypercyanotic spells (59 ± 21° vs 48 ± 13°, P = .023) and the need for neonatal surgery (67 ± 13° vs 48 ± 16°, P = .004). The positive and negative predictive values of hypercyanotic spells for conal septal angles ≥60° were 64% and 78%, respectively. Importantly, Doppler right ventricular outflow tract gradient at initial echocardiography, degree of aortic dextroposition, and pulmonary or aortic valve size were not associated with these outcomes. CONCLUSIONS: A wider conal septal angle is associated with the occurrence of hypercyanotic spells and the need for neonatal surgery.

Canine brachycephalic airway syndrome: pathophysiology, diagnosis, and nonsurgical management.

Canine brachycephalic airway syndrome is a progressive disease that affects many brachycephalic dogs. This article describes the components of this syndrome and focuses on acute emergency management and long-term conservative management of these patients. Surgical management is described in a companion article.

Resultados de la utilización de antirreflujo laparoscópico para la prevención de los episodios de apnea, bradicardia y desaturación / Results of the use of laparoscopic anti-reflux procedure for the prevention of episodes of apnea, bradycardia and desaturation

En 1986, el Instituto Americano de la Salud definió los ApparentLife-Threatenig Events (ALTEs) como “aquellos episodios escalofriantes para el observador que se caracterizan por una combinación de apneas (centrales u obstructivas), cambios en la coloración (cianosis, palidez, congestiva) y cambios marcados en el tono muscular (hipotonía), asfixia o atragantamiento”. A pesar de que su exacta etiología sigue siendo un misterio, son muchos los centros que relacionan los ALTE con la enfermedad por reflujo gastroesofágico (ERGE), recomendándose, casi sistemáticamente, tratamiento médico de la ERGE a los pacientes con ALTE. Sin embargo hay muy pocos trabajos en la literatura que muestren la eficacia del tratamiento quirúrgico de los pacientes con ALTE y ERGE. Se realizó una revisión retrospectiva entre2000 y 2008 de aquellos pacientes con ALTE a los que se les realizó técnica antirreflujo gastroesofágico. El estudio incluyó la realización de estudio baritado con técnica de sifonaje, pH metría y endoscopia laríngea, digestiva y (..) (AU)

In 1986 the National Institutes of Health Consensus Development Conference on Infantile Apnea and Home Monitoring defined the Apparent Life Threatening Events (ALTEs) as those frightening episodes for the observer which are determined by a combination of apnea (centralor obstructive), changes in colour (cianosis, congestive pallor) and marked changes in muscular tone, asphyxia. Despite the fact that its cause still remains unknown, many centres relate ALTE with gastroesophageal reflux disease (GERD) and therefore recommend medical treatment of GERD to those patients with ALTE. However there are very few articles that proof the efficacy of surgical treatment in patients with ALTE and GERD. We carried out a retrospective review between2000 and 2008 of those patients with ALTE who underwent a laparoscopic antirreflux procedure. The study included the realization of contrast x-ray, pHmetry and laryngeal, digestive and bronchial endoscopy. During this period antirreflux (with either Nissen or D’Or technique) procedure was carried out (.. ) (AU)

Therapeutic methods used in patients with Eisenmenger syndrome.

Patients with Eisenmenger syndrome form a small percentage of congenital heart disease patients. The rarity of this syndrome, combined with its complex pathophysiology, account for the insufficient understanding of the principles underlying its proper treatment. The main clinical symptoms are: cyanosis due to secondary erythrocytosis, resulting in increased blood viscosity, iron deficiency anemia (enhanced by unnecessary phlebotomies), blood clotting disturbances, heart failure and serious supraventricular and ventricular arrhythmias. Recent decades have seen developments in pulmonary hypertension pathophysiology which have led to the introduction of new groups of drugs: prostacycline analogs (Epoprostenol, Treprostinil, Beraprost, Illoprost), phosphodiesterase inhibitors (Sildenafil, Tadalafil), endothelin receptor antagonists (Bosentan, Sitaxantan, Ambrisentan) and nitric oxide. These drugs should be administered to patients in III-IV NYHA class. Despite successful early results, the therapeutic effect on patients with Eisenmenger syndrome has not been conclusively established. Our therapeutic efforts should be directed mainly towards preventing complications. As a rule, we should avoid agents with no established therapeutic efficacy and try to alleviate symptoms without any additional risk, so as not to disrupt the existing clinical balance.

Sedation of hypercyanotic spells in a neonate with tetralogy of Fallot using dexmedetomidine.

OBJECTIVE: Sedation is an important step in the management of patients with hypercyanotic spells associated with tetralogy of Fallot (TOF) to ameliorate and prevent recurrence of cyanosis. This case report illustrates the effectiveness of dexmedetomidine-induced sedation in the management of hypercyanotic spells in a neonate with TOF. DESCRIPTION: An 8-day-old term newborn patient with TOF showed hypercyanotic spells, as indicated by an abrupt decrease in arterial saturation (SpO2) level measured by a pulse oximeter from 80% to as low as 50%, when the patient became irritable and agitated. We started continuous infusion of dexmedetomidine at a dose of 0.2 microg/kg/min without a loading bolus injection. About half an hour after commencement of dexmedetomidine infusion, the patient reached an acceptable level of sedation, together with a drop in heart rate by approximately 20 beats/min. There was no apparent respiratory depression or marked change in blood pressure. SpO2 was also stable during dexmedetomidine infusion. The patient underwent a successful Blalock-Taussig shunt operation on the next day of admission. COMMENTS: Dexmedetomidine may be useful for the management of hypercyanotic spells in pediatric patients with TOF.

O uso de dexmedetomidina na sedação de crises hipercianóticas em um recém-nascido com tetralogia de Fallot / Sedation of hypercyanotic spells in a neonate with tetralogy of Fallot using dexmedetomidine

OBJETIVO: A sedação é um passo importante para aliviar e prevenir a recorrência de cianose no manejo de pacientes com crises hipercianóticas associadas à tetralogia de Fallot (T4F). Este relato de caso ilustra a eficácia da sedação induzida por dexmedetomidina no manejo de crises hipercianóticas em um recém-nascido com T4F. DESCRIÇÃO: Um paciente recém-nascido a termo de 8 dias de idade com T4F apresentava crises hipercianóticas, indicadas por quedas abruptas no nível de saturação arterial (SpO2), medido por um oxímetro de pulso, de 80 por cento até 50 por cento, quando o paciente ficava agitado ou irritável. Nós começamos a infusão contínua de dexmedetomidina em uma dosagem de 0,2 µg/kg/min sem injeção de ataque em bolus. Cerca de meia hora depois do início da infusão de dexmedetomidina, o paciente atingiu um nível aceitável de sedação, e sua freqüência cardíaca diminuiu aproximadamente 20 batidas por minuto. Não houve nenhuma depressão respiratória aparente ou mudança acentuada em sua pressão arterial. A SpO2 também continuou estável durante a infusão de dexmedetomidina. No dia seguinte à sua hospitalização, o paciente passou com sucesso por uma operação de anastomose de Blalock-Taussig. COMENTÁRIOS: A dexmedetomidina pode ser útil no manejo de crises hipercianóticas em pacientes pediátricos com T4F.

OBJECTIVE:Sedation is an important step in the management of patients with hypercyanotic spells associated with tetralogy of Fallot (TOF) to ameliorate and prevent recurrence of cyanosis. This case report illustrates the effectiveness of dexmedetomidine-induced sedation in the management of hypercyanotic spells in a neonate with TOF. DESCRIPTION: An 8-day-old term newborn patient with TOF showed hypercyanotic spells, as indicated by an abrupt decrease in arterial saturation (SpO2) level measured by a pulse oximeter from 80 percent to as low as 50 percent, when the patient became irritable and agitated. We started continuous infusion of dexmedetomidine at a dose of 0.2 µg/kg/min without a loading bolus injection. About half an hour after commencement of dexmedetomidine infusion, the patient reached an acceptable level of sedation, together with a drop in heart rate by approximately 20 beats/min. There was no apparent respiratory depression or marked change in blood pressure. SpO2 was also stable during dexmedetomidine infusion. The patient underwent a successful Blalock-Taussig shunt operation on the next day of admission. COMMENTS: Dexmedetomidine may be useful for the management of hypercyanotic spells in pediatric patients with TOF.

Placement of a continuous-flow ventricular assist device in the failing ventricle of an adult patient with complex cyanotic congenital heart disease.

For patients with end-stage heart failure and contraindications to transplantation, insertion of a continuous-flow left ventricular assist device (LVAD) is an effective treatment strategy. We present a case of LVAD insertion in a 46-year-old man with cyanotic complex congenital heart disease and an extensive surgical history who presented with failure of his systemic ventricle. The insertion of an LVAD in our patient restored cardiac output and improved cyanosis and native ventricular function. As the number of patients with congenital heart defects surviving to adulthood increases, destination LVAD therapy may be increasingly considered as an alternative.

Conversion from total cavopulmonary shunt to Fontan circulation: improved cyanosis with an 11-year interval.

We experienced a conversion case from total cavopulmonary shunt (TCPS) to the Fontan circulation with an 11-year interval in the left isomerism and an interruption of the inferior caval vein. Marked cyanosis (pulse oximetry measuring 74%) progressed 8 years after TCPS because of the prominent development of bilateral pulmonary arteriovenous fistula (PAVF), which was diminished after the Fontan conversion, and recent pulse oximetry measured 95% 22 months after the conversion. We believe that this report is a case with the longest interval from TCPS to Fontan in which PAVF was diminished and marked cyanosis was improved.

Safe reduction in administration of naloxone to newborn infants: an observational study.

BACKGROUND: Naloxone, a specific opiate antagonist, is widely used during neonatal resuscitation to reverse possible opiate-induced respiratory depression. AIM: To determine the frequency with which naloxone is administered when resuscitation guidelines are conscientiously followed and to document any effect on respiratory morbidity. METHODS: Perinatal data including naloxone administration and respiratory morbidity were collected retrospectively, and compared with prospectively collected data following the introduction of "Good Practice" guidelines. RESULTS: There were 500 deliveries in the retrospective arm of the study and 1000 deliveries in the prospective arm. Although a similar proportion of women received opiates in labour in the two periods of study, there was a marked reduction in the use of naloxone when the guidelines were introduced (11% of opiate-exposed deliveries compared to 0.2%). There was no significant effect on respiratory morbidity with the change in practice. CONCLUSION: Naloxone is rarely needed to reverse the effects of opiates in newborn infants, and its use can be curtailed by following current resuscitation guidelines without increasing respiratory morbidity.

Cyanotic breath-holding spell: a life-threatening complication after radical resection of a cervicomedullary ganglioglioma.

Cyanotic breath-holding spell is a benign and self-limiting disease of young children but occasionally associated with sudden, unexpected death. The authors report a rare case in a 2-year-old girl with a severe form that started after radical resection of a cervicomedullary ganglioglioma. She was admitted to our hospital because of delayed and unstable gait. Since magnetic resonance imaging showed a cervicomedullary tumor, she underwent a radical resection and histology showed the tumor to be a ganglioglioma. Postoperatively, the function of the lower cranial nerves and cerebellum deteriorated and hemiparesis on the left became apparent, but she returned to the preoperative state in a few months. In addition, mild sleep apnea (Ondine curse) and severe cyanotic breath-holding spells occurred. The former responded to medication but the latter failed and continued several times per day with a rapid onset and progression of hypoxemia, loss of consciousness, sweating and opisthotonos. Five months after the operation, the patient returned home with a portable oxygen saturation monitor equipped with an alarm. This case indicates that cyanotic breath-holding spell, as well as sleep apnea, is critical during the early postoperative period. This is the first report observing that such spells may occur as a complication of radical resection of a cervicomedullary tumor.

Does the site of insertion of a systemic-pulmonary shunt influence growth of the pulmonary arteries?

BACKGROUND: The modified Blalock-Taussig shunt is a common palliative procedure for children with cyanotic congenital heart disease. The distal shunt anastomosis can be done to a branch pulmonary artery or to the main pulmonary artery. The purpose of this study was to determine if the site of shunt connection influences pulmonary artery growth. METHODS: The records of 101 patients with a modified Blalock-Taussig shunt undergoing a subsequent cardiac catheterization between January 2000 and April 2002 were retrospectively reviewed. From the cineangiograms, the diameters of the right and left pulmonary arteries at their first branching and the diameter of the descending aorta at the diaphragm were measured. RESULTS: If the distal shunt anastomosis was to the right pulmonary artery and there was no antegrade pulmonary flow then the left pulmonary artery was significantly smaller than if the distal connection was to the main pulmonary artery (p = 0.009). Absence of antegrade pulmonary blood flow resulted in significantly smaller right and left pulmonary artery size in general (p < 0.001). No significant differences in pulmonary artery growth were found with respect to gender, anatomic subtype, proximal shunt site, use of cardiopulmonary bypass or size of shunt. By multiple regression analysis absence of antegrade flow and the presence of right-sided shunts were statistically significant predictors of smaller left pulmonary artery and size discrepancy between right and left pulmonary artery. CONCLUSIONS: These data suggest that in the absence of antegrade pulmonary blood flow, a modified Blalock-Taussig shunt to the main pulmonary artery may promote more uniform branch pulmonary artery growth.

Partial hepatic vein diversion in pulmonary arteriovenous malformations in congenital heart disease.

The late appearance of pulmonary arteriovenous malformations after operations for complex congenital cardiac conditions may be explained in many ways. The necessity of hepatic blood flow to the lungs is now generally accepted for carrying some labile substance that is secreted by the liver and that has not yet been identified. Rerouting of hepatic blood to the lungs in cardiac patients can be accomplished with different methods, most of which are predisposed to thrombosis because of the slow flow in the tunnel. My colleagues and I describe a case of partial diversion of hepatic blood into the pulmonary circulation and suggest a strategy to decrease the likelihood of conduit thrombosis and to treat pulmonary arteriovenous malformations.