Minimally invasive repair of Morgagni hernia - A multicenter case series.

Children may benefit from minimally invasive surgery (MIS) in the correction of Morgagni hernia (MH). The present study aims to evaluate the outcome of MIS through a multicenter study. National institutions that use MIS in the treatment of MH were included. Demographic, clinical and operative data were analyzed. Thirteen patients with MH (6 males) were operated using similar MIS technique (percutaneous stitches) at a mean age of 22.2±18.3 months. Six patients had chromosomopathies (46%), five with Down syndrome (39%). Respiratory complaints were the most common presentation (54%). Surgery lasted 95±23min. In none of the patients was the hernia sac removed; prosthesis was never used. In the immediate post-operative period, 4 patients (36%) were admitted to intensive care unit (all with Down syndrome); all patients started enteral feeds within the first 24h. With a mean follow-up of 56±16.6 months, there were two recurrences (18%) at the same institution, one of which was repaired with an absorbable suture; both with Down syndrome. The application of MIS in the MH repair is effective even in the presence of comorbidities such as Down syndrome; the latter influences the immediate postoperative recovery and possibly the recurrence rate. Removal of hernia sac does not seem necessary. Non-absorbable sutures may be more appropriate.

Thoracoscopy in the management of pediatric empyemas.

INTRODUCTION: Thoracoscopy is increasingly being used in the treatment of empyema. This study assesses feasibility, efficacy and safety in children. MATERIAL AND METHODS: Clinical files of patients who underwent primary thoracoscopy for empyema between 2006 and 2014 were reviewed. Demographic, clinical and surgical data were analyzed and a comparison between the period before (period1) and after (period2) the learning curve was performed. RESULTS: Ninety-one patients (53 males, 58%) were submitted to thoracoscopy at a median age of 4 years. There were 19 conversions to thoracotomy with a steady decrease of conversion rate until 2009 (period1) and no conversions thereafter (period2). There was no difference in any of the analyzed parameters between patients submitted to thoracoscopy alone and those requiring conversion in period1. Six cases (6.6%) needed redo-operation (five in period2) and thoracotomy was the elected approach in four. Necrotizing pneumonia was present in 60% of the reoperated cases; in other words, in period2 3 out of 9 cases with necrotizing pneumonia required reintervention (p=0.07). Thoracotomy was avoided in sixty-eight (75%) patients (62% in period1 versus 92% in period2, p=0.001). DISCUSSION AND CONCLUSIONS: Thoracoscopic approach for empyema is feasible and safe avoiding a significant number of thoracotomies after a short learning curve. An increase of reintervention rate should be expected, but throracoscopy alone is effective in the great majority of the cases. Necrotizing pneumonia may be associated with a higher risk of reintervention, as it is a contra-indication to thoracoscopy and probably surgery.

Neonatal extracorporeal membrane oxygenation: Initial experience of Hospital de São João.

The purpose of this series is to report the initial ECMO experience of the Neonatal Intensive Care Unit of Hospital de São João. The first three clinical cases are reported. Case report 1: a 39 weeks gestational age girl with severe lung hypoplasia secondary to a bilateral congenital diaphragmatic hernia. Case report 2: a 39 weeks gestational age girl with a right congenital diaphragmatic hernia and a tracheal stenosis. Case report 3: a 34 weeks gestational age boy, with 61 days of life, with a Bordetella pertussis pneumonia, severe pulmonary hypertension, shock, hyperleukocytosis and seizures.

The developmental stage determines the distribution and duration of gene expression after early intra-amniotic gene transfer using lentiviral vectors.

Gene transfer after intra-amniotic injection has, in general, been of low efficiency and limited to epithelial cells in the skin, pulmonary and gastrointestinal system. We have recently shown that early gestational administration results in a more efficient gene transfer to developmentally accessible stem cell populations in the skin and eye. In this study we present a comprehensive analysis of patterns of tissue expression seen after early intra-amniotic gene transfer (IAGT) using lentiviral vectors. To assess the influence of developmental stage on tissue expression, injections were administered from the late head fold/early somite stage (E8) to E18. In early gestation (E8-10), green fluorescent protein (GFP) expression was observed in multiple organs, derived from all three germ layers. Remarkably, GFP expression was observed in tissues derived from mesoderm and neural ectoderm at E8, whereas expression was limited to only epithelial cells of ectoderm- and endoderm-derived organs after E11. The amount and duration of gene expression was much higher after IAGT at early gestational time points. The observed temporal patterns of gene expression correspond to the predicted developmental accessibility of organ-specific cell populations. This model may be useful for the analyses of mechanisms of genetic and/or developmental disease and for the development of prenatal gene therapy for specific disorders.

Effects of TNF-alpha blockade in monocrotaline-induced pulmonary hypertension.

INTRODUCTION: TNF-alpha blockade in ischemic heart failure is still the subject of debate since clinical trials show conflicting results. However, its benefit in heart failure secondary to pulmonary hypertension has yet to be determined. It has been reported that transgenic rats overexpressing TNF-alpha develop pulmonary hypertension. The aim of this study was to assess the morphologic and hemodynamic effects of administration of an anti-TNF-alpha monoclonal antibody (etanercept) in rats with monocrotaline (MCT)-induced pulmonary hypertension. METHODS: Adult Wistar rats were injected with MCT (60 mg/Kg sc), or vehicle only (day 0). Beginning one day later, the animals were randomly treated with etanercept (ETC, 0.03 mg/Kg sc, three times a week) or with a similar volume of vehicle. The study thus had four groups: Ctrl (n = 6), Ctrl + ETC (n = 6), MCT (n = 6) and MCT + ETC (n = 6). On days 22-23, the rats were instrumented to record right ventricular systolic and end-diastolic pressures, dP/dtmax and tau. At the end of each experiment the heart and lungs were weighed. RESULTS AND CONCLUSIONS: Chronic administration of etanercept induced only a slight increase in relaxation velocity, with no effect on other hemodynamic parameters, including pulmonary hypertension, and no reduction in right ventricular hypertrophy. These results suggest that etanercept does not lead to a significant improvement in heart failure secondary to pulmonary hypertension.

Cardiac remodeling and dysfunction in nephrotic syndrome.

There is an increased incidence of heart disease in patients with chronic nephrotic syndrome (NS), which may be attributable to the malnutrition and activated inflammatory state accompanying the sustained proteinuria. In this study, we evaluated renal function, cardiac morphometry, contractile function, and myocardial gene expression in the established puromycin aminonucleoside nephrosis rat model of NS. Two weeks after aminonucleoside injection, there was massive proteinuria, decreased creatinine clearance, and a negative sodium balance. Skeletal and cardiac muscle atrophy was present and was accompanied by impaired left ventricular (LV) hemodynamic function along with decreased contractile properties of isolated LV muscle strips. The expression of selected cytokines and proteins involved in calcium handling in myocardial tissue was evaluated by real time polymerase chain reaction. This revealed that the expression of interleukin-1beta, tumor necrosis factor-alpha, and phospholamban were elevated, whereas that of cardiac sarco(endo)plasmic reticulum calcium pump protein was decreased. We suggest that protein wasting and systemic inflammatory activation during NS contribute to cardiac remodeling and dysfunction.

Morphologic, molecular and hemodynamic cardiac alterations in a model of nephropathy induced by puromycin aminonucleoside.

INTRODUCTION: Proteinuria and decreased glomerular filtration rate are assuming increased importance in defining cardiovascular risk in chronic renal insufficiency. The aim of this work was to study morphologic, molecular and hemodynamic cardiac alterations in an animal model of proteinuria and renal insufficiency induced by puromycin aminonucleoside (PAN). METHODS: Normotensive rats (n = 14) were injected with PAN (150 mg/kg, i.p.) or with vehicle. Blood pressure was measured daily and the animals were placed in metabolic cages for evaluation of urinary excretion of sodium, protein and creatinine. Fourteen days after PAN administration left ventricular hemodynamics were evaluated through a pressure tip micromanometer and heart morphology was examined. Transmural samples of left ventricle were then taken for mRNA quantification of SERCA2a, phospholamban (PLB), insulin-like growth factor 1 (IGF-1) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH). RESULTS: The animals treated with PAN presented a decrease in creatinine clearance (14th day: 2.24 +/- 0.32 vs. 4.51 +/- 1.08 ml/min) and an increase in proteinuria (14th day: 51.0 +/- 9.0 vs. 3.8 +/- 0.7 mg/mg creatinine), without changes in systolic (14th day: 151 +/- 7 vs. 141 +/- 6 mmHg) or diastolic blood pressure (14th day: 85 +/- 7 vs. 86 +/- 3 mmHg), These alterations were accompanied by cardiac atrophy with decreased left ventricular contractility. A reduction in the SERCA2a/PLB mRNA ratio was observed without significant alteration in the expression of IGF-1 in the left ventricle. CONCLUSIONS: PAN-induced nephropathy is accompanied by cardiac atrophy, left ventricular dysfunction and alterations in the expression of genes involved in myocardial calcium kinetics. These findings were not accompanied by increases in blood pressure and may contribute to our understanding of the increased cardiovascular risk in chronic renal insufficiency.

Ghrelin as a novel locally produced relaxing peptide of the iris sphincter and dilator muscles.

Ghrelin is a recently described acylated peptide, which works as a somatosecretagogue and has described effects on the smooth, skeletal and cardiac muscle. We examined the production and effects of ghrelin on relaxation of the iris muscles. Contractile effects of 1-5 human ghrelin (frGhr, 10(-9)-6 x 10(-5)M) and 1-5 human des-octanoyl-ghrelin (d-frGhr; 10(-9)-6 x 10(-5)M) were tested on iris rabbit sphincter (n=11 frGhr; n=7 d-frGhr), dilator (n=6 frGhr; n=6 d-frGhr) and rat sphincter (n=6 frGhr; n=8 d-frGhr) precontracted muscles. On rabbit sphincter the effect of frGhr was also tested in presence of: i) L-NA (10(-5)M; n=7); ii) indomethacin (10(-5)M; n=7); iii) DLys(3)GHRP6 (10(-4)M; n=6); and iv) apamin+carybdotoxin (10(-6)M; n=6). Furthermore, on rabbit dilator the effect of frGhr was tested in presence of DLys(3)GHRP6 (10(-4)M; n=7). Finally, ghrelin mRNA production was assessed by "in situ" hybridization in Wistar rat eyes (n=8). In all muscles, frGhr promoted a concentration-dependent relaxation, maximal at 6 x 10(-5)M, 1.5-3 min after its addition, decreasing tension by 34.1+/-12.1%, 25.8+/-4.8% and 52.1+/-10.3% in the rabbit sphincter, dilator and rat sphincter, respectively. In the rabbit sphincter the relaxing effects of frGhr were: (i) enhanced in presence of DLys(3)GHRP6 (118.1+/-21.1%); (ii) blunted by indomethacin; and (iii) not altered by apamin+carybdotoxin (36.4+/-14.4%) or L-NA (52.4+/-11.4%). Relaxing effects of d-frGhr in rabbit (43.3+/-5.2%) and rat (77.1+/-15.3%) sphincter muscles were similar to those of frGhr. In rabbit dilator muscle, d-frGhr did not significantly alter active tension and the relaxing effect of frGhr was blunted by GHSR-1a blockage. Ghrelin mRNA was identified in iris posterior epithelium. In conclusion, ghrelin is a novel, locally produced, relaxing agent of iris dilator and sphincter muscles, an effect that is mediated by GHSR-1a in the former, but not in the latter. Furthermore, in the sphincter it seems to be mediated by prostaglandins, but not by NO or K(Ca) channels.

Differential right and left ventricular diastolic tolerance to acute afterload and NCX gene expression in Wistar rats.

This study evaluated right ventricular (RV) and left ventricular (LV) diastolic tolerance to afterload and SERCA2a, phospholamban and sodium-calcium exchanger (NCX) gene expression in Wistar rats. Time constant tau and end diastolic pressure-dimension relation (EDPDR) were analyzed in response to progressive RV or LV afterload elevations, induced by beat-to-beat pulmonary trunk or aortic root constrictions, respectively. Afterload elevations decreased LV- tau, but increased RV-tau. Whereas LV- tau analyzed the major course of pressure fall, RV- tau only assessed the last fourth. Furthermore, RV afterload elevations progressively upward shifted RV EDPDR, whilst LV afterload elevations did not change LV-EDPDR. SERCA2a and phospholamban mRNA were similar in both ventricles. NCX-mRNA was almost 50 % lower in RV than in LV. Left ventricular afterload elevations, therefore, accelerated the pressure fall and did not induce diastolic dysfunction, indicating high LV diastolic tolerance to afterload. On the contrary, RV afterload elevations decelerated the late RV pressure fall and induced diastolic dysfunction, indicating small RV diastolic tolerance to afterload. These results support previous findings relating NCX with late Ca(2+) reuptake, late relaxation and diastolic dysfunction.

Pattern of right ventricular pressure fall and its modulation by afterload.

Pattern of right ventricular pressure (RVP) fall and its afterload dependence were examined by analyzing ventricular pressure curves and corresponding pressure dP/dt phase planes obtained in both ventricles in the rat heart in situ. Time and value of dP/dt(min), and the time constant tau were measured at baseline and during variable RV afterload elevations, induced by beat-to-beat pulmonary trunk constrictions. RVP and left ventricular pressure (LVP) decays were divided into initial accelerative and subsequent decelerative phases separated by corresponding dP/dt(min). At baseline, LVP fall was decelerative during 4/5 of its course, whereas only 1/3 of RVP decay occurred in a decelerative fashion. During RV afterload elevations, the absolute value of RV-dP/dt(min) and RV-tau increased, whilst time to RV dP/dt(min) decreased. Concomitantly, the proportion of RVP decay following a decelerative course increased, so that in highly RV afterloaded heartbeats RVP fall became more similar to LVP fall. In conclusion, RVP and LVP decline have distinct patterns, their major portion being decelerative in the LV and accelerative in the RV. In the RV, dP/dt(min), tau and the proportional contribution of accelerative and decelerative phases for ventricular pressure fall are afterload-dependent. Consequently, tau evaluates a relatively much shorter segment of RVP than LVP fall.

Distinct load dependence of relaxation rate and diastolic function in Oryctolagus cuniculus and Ratus norvegicus.

This study investigated potential differences on load dependence of relaxation rate and diastolic function between Oryctolagus cuniculus and Ratus norvegicus, which have constitutive differences in the mechanisms involved in myocardial inactivation. Load dependence of relaxation rate and diastolic function were evaluated with the response of left ventricular time constant tau and diastolic pressure-dimension relation to beat-to-beat aortic constrictions in open-chest rabbits and rats. Afterload levels were normalized, being expressed as a percentage of peak isovolumetric pressure (relative load). In control heartbeats, relaxation rate and diastolic function were similar in the two animal species. They presented, however, distinct responses to afterload elevations. In rabbits, time constant decreased approximately 7% and diastolic pressure-dimension relation remained unchanged when afterload was elevated to a relative load of 73-76%. Above this afterload level, a significant deceleration of relaxation rate (increase of time constant) and an upward shift of diastolic pressure-dimension relation were observed. In rats, afterload elevations accelerated pressure fall up to a relative load of 97-100% and no afterload-induced shift of the diastolic pressure-dimension relation was observed. This study provides, therefore, evidence that Oryctolagus cuniculus has lower afterload reserve of myocardial relaxation and diastolic function than Ratus norvegicus.

[Interaction between load and beta-adrenergic stimulation in the modulation of diastolic function]. / Interacção da carga com a estimulação beta-adrenérgica na modulação da função diastólica.

INTRODUCTION AND OBJECTIVES: Excessive afterload induces an upward shift of the diastolic pressure-volume relation. This diastolic dysfunction was attributed to the concomitant slowing of relaxation. The present study investigated to what extent beta-adrenergic stimulation could influence this effect. METHODS: Beat-to-beat afterload elevations were induced in anaesthetised open-chest rabbits (n = 7) by narrowing the ascending aorta, to increase peak left ventricular pressure (LVPmax) from control up to isovolumetric. Afterload elevations were performed at baseline and during infusion of isoproterenol (0.15 mg/kg/min). RESULTS: At baseline, LVPmax increased from 84 +/- 7 in the control beat to 154 +/- 10 mmHg in the isovolumetric beat, while during isoproterenol it increased from 88 +/- 4 to 184 +/- 11 mmHg (p < 0.01). After an isovolumetric beat, diastolic dysfunction was 7.9 +/- 1.5 mmHg at baseline and 2.6 +/- 0.5 mmHg during isoproterenol (p < 0.01). At all afterload levels, isoproterenol accelerated LVP fall (decreased the time constant tau), decreased the predicted time to completion of relaxation but did not influence the time available for the ventricle to relax. CONCLUSIONS AND IMPLICATIONS: Afterload induced diastolic dysfunction was attenuated by beta-adrenergic stimulation. These results, along with the inotropic and lusitropic effects of isoproterenol, may contribute to the acute improvement of cardiac function induced by beta-adrenergic stimulation. It may also help to explain the response to physical exercise and the pathophysiology of diastolic dysfunction in heart failure.

[The effects of endothelin-1 on myocardial function]. / Efeitos da endotelina-1 sobre a função miocárdica.

INTRODUCTION: Endothelin-1 (ET-1) has potent vasoconstrictor, growth promoting and positive inotropic properties, with increased plasma levels in heart failure (HF). With regard to the cardiac effects of ET-1, most studies have not been able to differentiate its effects on the intrinsic properties of the myocardium from the secondary effects resulting from load changes and coronary vasoconstriction. This study investigated the myocardial effects of ET-1. METHODS: The study was performed on isolated rabbit papillary muscles (n = 9), before and after the addition of ET-1 (10 nM) to the superfusing solution (Krebs-Ringer; 1.25 nM Ca2+; 35 degrees C). One isotonic, one isometric and two afterloaded-isotonic twitches were recorded and analyzed. Only significant results (mean +/- SE, p < 0.05) are given, expressed as delta % baseline. RESULTS: ET-1 induced an increase of AT (147 +/- 33%), dT/dtmax (154 +/- 39%) and dT/dtmin (145 +/- 38%), while the duration of the twitch did not vary significantly. In addition, after ET-1, RT at the end of the isometric twitch decreased by 19 +/- 3%, when compared with the control and to its value at the beginning of the twitch. CONCLUSIONS: This study showed that, in addition to the well-known positive inotropic effect, ET-1 improves diastolic function by accelerating relaxation rate (dT/dtmin) and decreasing RT. These results may have important implications in the pathophysiology of HF.