Effect of dexmedetomidine on perioperative hemodynamics and organ protection in children with congenital heart disease: A randomized controlled trial.

BACKGROUND: This study aimed to investigate the effects of dexmedetomidine (Dex) on hemodynamics and organ protection in congenital heart disease (CHD) children who underwent open-heart surgery under cryogenic cardiopulmonary bypass. METHODS: Ninety children were randomly allocated to group C (0.9% saline 0.2 µg/kg/hour), group D1 (Dex 0.2 µg/kg/hour), and group D2 (Dex 0.4 µg/kg/hour) (n = 30 per group). All participants received fentanyl, propofol and 1% sevoflurane for anesthesia induction. Hemodynamic data were measured from T0 (before the induction) to T7 (30 minutes after extubation). The difference of arterial internal jugular vein bulbar oxygen difference and cerebral oxygen extraction ratio were calculated according to Fick formula. Enzyme-linked immunosorbent assay was performed to detect the serum myocardial, brain and kidney injury markers. The incidence of acute kidney injury (AKI) was calculated by serum creatinine level. Tracheal extubation time, postoperative pain score and emergence agitation score were also recorded. RESULTS: Compared with group C, group D1, and D2 exhibited reduction in hemodynamic parameters, myocardial and brain injury indicators, and tracheal extubation time. There were no significant differences in blood urea nitrogen and neutrophil gelatinase-associated lipocalin or incidence of AKI among the 3 groups. Besides, the incidence of tachycardia, nausea, vomiting and moderate agitation, and the FLACC scale in group D1 and D2 were lower than those in group C. Moreover, Dex 0.4 g/kg/hour could further reduce the dosage of fentanyl and dopamine compared with Dex 0.2 g/kg/hour. CONCLUSIONS: Dex anesthesia can effectively maintain hemodynamic stability and diminish organ injuries in CHD children.

Down syndrome, severe psoriasis, and increased risk for cardiovascular events.

Down syndrome is a genetic disorder known to cause many complications with lifelong effects. Patients with Down syndrome are known to produce excess interferon gamma, a major culprit of psoriasis formation and severity. Both conditions increase patient risk for major cardiovascular events; however, a potential association between Down syndrome and severe psoriasis has not been well studied. This article discusses a patient with Down syndrome and worsening plaque psoriasis who died of an acute myocardial infarction.

Role of Overexpressed Transcription Factor FOXO1 in Fatal Cardiovascular Septal Defects in Patau Syndrome: Molecular and Therapeutic Strategies.

Patau Syndrome (PS), characterized as a lethal disease, allows less than 15% survival over the first year of life. Most deaths owe to brain and heart disorders, more so due to septal defects because of altered gene regulations. We ascertained the cytogenetic basis of PS first, followed by molecular analysis and docking studies. Thirty-seven PS cases were referred from the Department of Pediatrics, King Abdulaziz University Hospital to the Center of Excellence in Genomic Medicine Research, Jeddah during 2008 to 2018. Cytogenetic analyses were performed by standard G-band method and trisomy13 were found in all the PS cases. Studies have suggested that genes of chromosome 13 and other chromosomes are associated with PS. We, therefore, did molecular pathway analysis, gene interaction, and ontology studies to identify their associations. Genomic analysis revealed important chr13 genes such as FOXO1, Col4A1, HMGBB1, FLT1, EFNB2, EDNRB, GAS6, TNFSF1, STARD13, TRPC4, TUBA3C, and TUBA3D, and their regulatory partners on other chromosomes associated with cardiovascular disorders, atrial and ventricular septal defects. There is strong indication of involving FOXO1 (Forkhead Box O1) gene-a strong transcription factor present on chr13, interacting with many septal defects link genes. The study was extended using molecular docking to find a potential drug lead for overexpressed FOXO1 inhibition. The phenothiazine and trifluoperazine showed efficiency to inhibit overexpressed FOXO1 protein, and could be potential drugs for PS/trisomy13 after validation.

[Protective effect of aminophylline on cerebral injury during cardiopulmonary bypass in infants].

OBJECTIVE: To investigate the protective effect of aminophylline on cerebral injury induced by cardiopulmonary bypass (CPB) in infants. METHODS: Forty patients who underwent ventricular septal defect within 3 years old were randomly divided into 2 groups(20 cases in each group).Aminophylline group:aminophylline (5 mg/kg) was injected slowly via the vein after anesthesia and maintained at a dose of 0.5 mg/(kg.h) until the end of CPB. CONTROL GROUP: aminophylline was replaced by Ringer's lactated solution. Samples were obtained at the beginning of CPB (T(1)),the end of CPB (T(2)),6 h (T(3)) and 24 h (T(4)) after the operation to measure S-100 beta protein, NSE, tumor necrosis factor-alpha (TNF-alpha), interleukin-8 (IL-8), and interleukin-10 (IL-10) concentration by ELISA in the 2 groups. RESULTS: Compared with the time point immediately before CPB, the S-100beta protein,NSE, TNF-alpha, and IL-8 concentration in the 2 groups began to increase with the start of CPB, reached a climax at the end of CPB (T(2)),decreased gradually 6 h after the termination of CPB(T(3)) and could not restore to the level before CPB at T(4)(24 h after the termination of CPB).IL-10 in the 2 groups both increased after the CPB. At T(2) and T(3), S-100beta protein,NSE, TNF-alpha, and IL-8 concentrations were significantly lower than those in the aminophylline group (P<0.05 or P<0.01), while IL-10 was just the opposite. CONCLUSION: There is cerebral damage induced by CPB. Aminophylline may play a protective role in cerebral injury by modulating the balance between the pro-inflammatory factor and anti-inflammatory factor to reduce the level of S-100beta protein and NSE during CPB and open cardiac surgeries.

Prenatal diagnosis of complete atrioventricular canal associated with tetralogy of Fallot.

A complete atrioventricular canal defect occurs when an embryonic common atrioventricular valve fails to divide completely into 2 common atrioventricular valves. Tetralogy of Fallot is an abnormal embryologic development in which an unequal conotruncal division results in a small pulmonary artery and a large aortic artery. We report a case of prenatal diagnosis of a complete atrioventricular canal defect associated with tetralogy of Fallot.

Long-term hemodynamic effects of nifedipine on congenital heart disease with Eisenmenger's mechanism in children.

The hemodynamic effect of long-term nifedipine medication was studied in 10 children, 3-12 years of age, five with ventricular septal defect and five with complete atrioventricular septal defect; all had Eisenmenger's reaction, seven also had Down's syndrome. They underwent heart catheterization prior to and during 1-4 years of nifedipine therapy. Fick's principle was used to calculate the ratio of pulmonary arterial pressure to aortic pressure (PAP/PAO), the ratio of pulmonary flow to aortic flow (QP/QS), as well as the ratio of pulmonary vascular resistance to aortic vascular resistance (RP/RS). In the seven children under 8.8 years, nifedipine caused a significant drop in PAP/PAO (p less than 0.004), a slight increase in arterial O2 saturation, a significant increase in QP/QS (p less than 0.02), and a decrease in RP/RS (p less than 0.02). The nifedipine effect was age related. On nifedipine, breathing oxygen resulted in, independent of age, a significant increase in QP/QS (p less than 0.003) and a significant decrease in PAP/PAO (p less than 0.04) and in RP/RS (p less than 0.003). Direct O2 consumption measurements before and during oxygen breathing in six patients demonstrated no significant change in RP, RS, QP, or QS indices. Nifedipine had a relaxing effect on the pulmonary vascular bed, especially in the younger child with Eisenmenger's mechanism. On nifedipine therapy, O2 produced a more complex hemodynamic reaction that was not restricted to the pulmonary circulation alone.

Uso de prostaglandina oral PGE2 en cardiopatías ductus dependientes (CDD)

Se presentan los resultados de un estudio prospectivo del uso de Prostaglandinas PGE2 vía oral en 30 pacientes con Cardiopatías Ductus Dependientes muy variables. Se encontró una dosis terapéutica entre 20 y 35 microgramos Kg/hr, debiendo iniciarse con 30-35 microgramos Kg/hr. A las pocas horas de iniciado el tratamiento (más o menos dos horas), se encontró marcada mejoría con estabilización de los pacientes. En los pacientes con obstrucción severa a la salida del Ventrículo Derecho se encontró un aumento de la PO2 de 10,5 Torr en promedio. Las prostaglandinas orales se pueden administrar por largos períodos de tiempo con pocos riesgos de complicación a las dosis señaladas y la tolerancia encontrada es muy buena. Todo lo anterior hace que las prostaglandinas PGE2 vía oral sean una útil posibilidad de tratamiento para los pacientes con Cardiopatías Ductus Dependientes

Short-term hemodynamic effects of hydralazine in infants with complete atrioventricular canal defects.

We evaluated the acute hemodynamic responses to hydralazine during cardiac catheterization in eight infants (ages 1.0 to 5.5 months) with congestive heart failure due to complete atrioventricular canal defect. Hydralazine administered intravenously (0.5 to 1.0 mg/kg body weight) increased heart rate and systemic blood flow and decreased mean right atrial pressure, systemic and pulmonic arterial pressures, systemic arteriolar resistance, and the ratio of pulmonary to systemic blood flow (p less than .05). The percentage of pulmonary flow contributed by shunted blood (percent left-to-right shunt; measured by indicator dilution) was decreased by hydralazine in six (mean = 85% before to 64% after hydralazine; p less than .01), but remained unchanged (79%) in two infants. The two infants with no change in percent left-to-right shunt had higher pulmonary arteriolar resistances (Rp) before hydralazine (mean = 12.8 vs 3.2 U/m2) and had greater declines in Rp (mean change = -5.1 vs + 0.3 U/m2) in response to hydralazine. Thus, if Rp does not fall, hydralazine reduces the percentage of left-to-right shunt over the short term and therefore might be useful for managing congestive heart failure in these infants. However, because the response varies, an evaluation of the short-term hemodynamic effects of hydralazine may be warranted in an attempt to select those infants who might respond favorably to long-term hydralazine therapy.

Acute effects of vasodilators on left-to-right shunts in infants and children.

Based on the favorable experience with vasodilator therapy in adult heart disease and the results of acute dogs experiments, we undertook the hemodynamic evaluation of hydralazine and phentolamine during diagnostic cardiac catheterization. We studied seven infants and children with left-to-right (leads to R) shunts at atrial, ventricular, or ductal levels to determine whether vasodilator therapy might be useful in the treatment of infants with congestive heart failure (CHF) due to large L leads to R shunts. Shunts, flows, and resistances were measured by the indicator dilution and Fick techniques before and after administration of the drug. At a dose sufficient to produce an effect, the shunt flow increased after each drug. There is no evidence from studies at cardiac catheterization of therapeutic efficacy for vasodilators in the treatment of CHF due to cardiac L leads to R shunts.

Prostaglandins: a possible regulator of muscle tone in the ductus arteriosus.

We have shown that E-type prostaglandins are potent relaxant of the lamb ductus arteriosus at low, but not high, oxygen tensions, and that their effect is possibly controlled by the rate of endogenous PG synthesis. These findings, together with the demonstration of the contractile effect of PG synthesis blockers on the hypoxic ductus in vitro and in vivo and of the relaxant effect of GSH in vitro, strongly suggest that E-type prostaglandins are responsible for maintaining ductus patency during fetal life. The endoperoxide intermediates may act in concert with PGEs. While our findings argue against the idea that PGF2alpha mediates the oxygen-induced constriction, they suggest that suppression of PGE activity in a high oxygen environment might be important to the initiation of ductus closure at birth. An extension of this concept is that continued patency of the ductus after birth results from either the excessive formation of PGEs or from the persistence of a "fetal-like" response of ductal muscle to endogenous or bloodborne PGEs, or both. The present scheme of PGE action is amenable to practical applications. Our work and that of Elliott et al. (15) prove that PGEs can be used to reopen a constricted ductus in children with cyanotic congenital heart disease, thus improving their change of survival during subsequent corrective surgery. Conversely, treatment with blockers of PG synthesis is envisaged as an alternative to surgery for closing a persistent ductus.