Virtual Reality Head-Mounted Display (HMD) and Preoperative Patient-Specific Simulation: Impact on Decision-Making in Pediatric Urology: Preliminary Data.

AIM OF THE STUDY: To assess how virtual reality (VR) patient-specific simulations can support decision-making processes and improve care in pediatric urology, ultimately improving patient outcomes. PATIENTS AND METHODS: Children diagnosed with urological conditions necessitating complex procedures were retrospectively reviewed and enrolled in the study. Patient-specific VR simulations were developed with medical imaging specialists and VR technology experts. Routine CT images were utilized to create a VR environment using advanced software platforms. The accuracy and fidelity of the VR simulations was validated through a multi-step process. This involved comparing the virtual anatomical models to the original medical imaging data and conducting feedback sessions with pediatric urology experts to assess VR simulations' realism and clinical relevance. RESULTS: A total of six pediatric patients were reviewed. The median age of the participants was 5.5 years (IQR: 3.5-8.5 years), with an equal distribution of males and females across both groups. A minimally invasive laparoscopic approach was performed for adrenal lesions (n = 3), Wilms' tumor (n = 1), bilateral nephroblastomatosis (n = 1), and abdominal trauma in complex vascular and renal malformation (ptotic and hypoplastic kidney) (n = 1). Key benefits included enhanced visualization of the segmental arteries and the deep vascularization of the kidney and adrenal glands in all cases. The high depth perception and precision in the orientation of the arteries and veins to the parenchyma changed the intraoperative decision-making process in five patients. Preoperative VR patient-specific simulation did not offer accuracy in studying the pelvic and calyceal anatomy. CONCLUSIONS: VR patient-specific simulations represent an empowering tool in pediatric urology. By leveraging the immersive capabilities of VR technology, preoperative planning and intraoperative navigation can greatly impact surgical decision-making. As we continue to advance in medical simulation, VR holds promise in educational programs to include even surgical treatment of more complex urogenital malformations.

Efficacy of Three Different Injection Techniques for the Endoscopic Treatment of Vesicoureteral Reflux (VUR) in Children: A Review of 10 Years of Experience.

Aim: To review our 10 years of experience with the endoscopic treatment of vesicoureteral reflux (VUR) in children, emphasizing the long-term efficacy of the "combined STING-HIT" technique. Materials and Methods: A retrospective study was performed including all children with symptomatic VUR undergoing the cystoscopic injection of bulking agents from January 2013 to December 2022 in our pediatric tertiary referral center. Three different endoscopic techniques were adopted: the "combined STING-HIT" technique, the STING technique, and the HIT technique. Treatment success was defined as symptom remission and VUR resolution on the voiding cystourethrogram (VCUG) performed at the 3-month follow-up. Results: In the study period, 140 (F:M = 64:76) patients and 228 ureters were treated at a median patient age of 3 (2.0-6.0) years. After a single endoscopic treatment, VUR resolved in 203 (88%) ureters. The VUR resolution rate after a single endoscopic treatment was 95% (n=70/74) in case of I-II VUR, 88% (n=87/99) in case of III VUR; 83% (n=38/46) in case of IV VUR; 89% (n=8/9) in case of V VUR (p-value: 0.174). Overall, one or two endoscopic treatments succeeded in 219 (96%) ureters. The overall VUR resolution rate following one or two endoscopic treatments was 100% (74/74) in case of I-II VUR, 93% (n=92/99) in case of III VUR; 96% (n=44/46) in case of IV VUR; 100% (n=9/9) in case of V VUR (p-value: 0.083). Despite not being statistically significant, the VUR resolution rate was higher for the "combined STING-HIT" technique, both after one (92%: n=110/119; versus 85%; n=62/73 versus 86%; n=31/36; p-value: 0.225) or two (98%: n=116/119; versus 95%; n=69/73 versus 94%; n=34/36; p-value: 0.469) endoscopic treatments. Conclusion: The endoscopic approaches were highly successful for the treatment of VUR in children. The "combined STING-HIT" technique was a safe and effective procedure, being associated with the higher resolution rate.

Case Report: Chronic pancreatitis in children as the cumulative effect of bilio-pancreatic abnormalities and genetic mutations.

Pancreatitis, in general, is a high-morbidity condition. Genetic conditions and anatomic variants are sometimes seen, especially in children, where biliary etiologies and alcohol are less common than in adults. The decision to intervene, the combined operative-endoscopic strategy, and the timing pose unique challenges. We report the case of a 10-year-old boy with PRSS1 mutation and pancreatic duct duplication, discussing the management and reviewing the recent reports in the Literature.

Minimal Access in Pediatric Surgery: An Overview on Progress towards Dedicated Instrument Developments and Anesthesiologic Advances to Enhance Safe Completion of Procedures.

Surgical techniques are evolving in Pediatric Surgery, especially in the area of minimal access surgery (MAS) where indications for applications are expanding. Miniaturization of instruments, using natural orifices, single incisions, or remotely controlled robot-assisted procedures, promises to increase the benefits of MAS procedures in pediatrics. Many pediatric pathologies are rare, and specialized surgical and anesthesiologic instruments are necessary to manage them, defined as "orphan devices", for which development and dissemination on the market are slowed down or sometimes hindered by regulatory standards and limiting financial conflicts of interest. In pediatric surgery, it is of utmost importance to work in a multidisciplinary way to offer a surgical path that is safe and supported by technological advances. For this reason, optimizing pediatric anesthesia is also a crucial factor where technological advances have made monitoring more precise, thereby enhancing safety in the operative room. The development of customized instruments and technologies should be supported by pediatric research and should be adapted to the individualities of the small patient. This overview outlines the importance of dedicated instruments developed for the safe completion of MAS procedures in pediatrics.

Leveraging User-Friendly Mobile Medical Devices to Facilitate Early Hospital Discharges in a Pediatric Setting: A Randomized Trial Study Protocol.

BACKGROUND: Mobile technology is increasingly prevalent in healthcare, serving various purposes, including remote health monitoring and patient self-management, which could prove beneficial to early hospital discharges. AIMS: This study investigates the transitional care program experience facilitating early discharges in a pediatric setting through the use of an easy-to-use mobile medical device (TytoCare™, TytoCare Ltd., Natanya, Israel). OUTCOMES: This study aims to assess the effectiveness of telehomecare in achieving complete resolution of diseases without readmission, compare the length of stay between intervention and standard care groups, and gather user and professional experiences. METHODS: A randomized open-label, controlled pilot study enrolled 102 children, randomly assigned to the telehomecare (TELE) group (n = 51, adopting early hospital discharge with continued home monitoring) or the standard-of-care (STAND) group (n = 51). Primary outcomes include complete disease resolution without readmission. Secondary objectives include recording a shorter length of stay in the intervention group. Surveys on user and professional experiences were conducted. A group of 51 children declining telemedicine services (NO-TELE) was also included. RESULTS: In the TELE group, 100% of children achieved complete disease resolution without readmission, with a median duration of stay of 4 days, significantly shorter than the 7 days in the STAND group (p = 0.01). The telemedicine system demonstrated efficient performance and high satisfaction levels. The NO-TELE group showed no significant differences in demographics or digital technology competence. Perceived benefits of telemedicine included time and cost savings, reduced hospital stays, and technology utility and usability. CONCLUSIONS: This study demonstrates that user-friendly mobile medical devices effectively facilitate early hospital discharges in a pediatric setting. These devices serve as a bridge between home and hospital, optimizing care pathways.

Duodenal stenosis, an unusual presentation of eosinophilic gastroenteritis: a case report.

Eosinophilic gastrointestinal diseases (EGIDs) are rare, chronic inflammatory disorders characterized by eosinophilic infiltration of the gastrointestinal tract. Symptoms and clinical presentations vary depending on the site and layer of the gastrointestinal wall infiltrated by eosinophils. Gastrointestinal obstruction is a serious, though uncommon, presentation. Management can be extremely challenging because of the rarity of the condition and the lack of robust scientific evidence. Current treatment approaches for EGIDs mainly focus on elimination diets, proton pump inhibitors and corticosteroids, which present high refractoriness rates. Novel targeted therapies are being investigated but not routinely used. Surgery should be avoided as far as possible; however, it may be the only option in gastrointestinal obstruction when long-term remission cannot be attained by any medical strategy. Herein we report the case of an adolescent boy affected by an eosinophilic gastrointestinal disease with progressive duodenal stenosis, refractory to medical therapy, who successfully benefitted from surgical management. He presented with a one-year history of gastrointestinal obstructive symptoms with feeding intolerance. After the diagnostic workup, he was diagnosed with an eosinophilic gastrointestinal disease (esophagitis and enteritis) with a duodenal involvement causing a progressive duodenal stenosis. Due to refractoriness to the conventional medical therapies and the consequent high impact on his quality of life, related both to the need for enteral nutrition and repeated hospitalizations, we decided to perform a gastro-jejunum anastomosis, which allowed us to obtain a clinical and endoscopic long-term remission. The early discussion of the case and the involvement of all experienced specialists, pediatricians and pediatric surgeons is essential.

Antenatal Determinants of Postnatal Renal Function in Fetal Megacystis: A Systematic Review.

Introduction: To evaluate the clinical usefulness of demographic data, fetal imaging findings and urinary analytes were used for predicting poor postnatal renal function in children with congenital megacystis. Materials and methods: A systematic review was conducted in MEDLINE's electronic database from inception to December 2023 using various combinations of keywords such as "luto" [All Fields] OR "lower urinary tract obstruction" [All Fields] OR "urethral valves" [All Fields] OR "megacystis" [All Fields] OR "urethral atresia" [All Fields] OR "megalourethra" [All Fields] AND "prenatal ultrasound" [All Fields] OR "maternal ultrasound" [All Fields] OR "ob-stetric ultrasound" [All Fields] OR "anhydramnios" [All Fields] OR "oligohydramnios" [All Fields] OR "renal echogenicity" [All Fields] OR "biomarkers" [All Fields] OR "fetal urine" [All Fields] OR "amniotic fluid" [All Fields] OR "beta2 microglobulin" [All Fields] OR "osmolarity" [All Fields] OR "proteome" [All Fields] AND "outcomes" [All Fields] OR "prognosis" [All Fields] OR "staging" [All Fields] OR "prognostic factors" [All Fields] OR "predictors" [All Fields] OR "renal function" [All Fields] OR "kidney function" [All Fields] OR "renal failure" [All Fields]. Two reviewers independently selected the articles in which the accuracy of prenatal imaging findings and fetal urinary analytes were evaluated to predict postnatal renal function. Results: Out of the 727 articles analyzed, 20 met the selection criteria, including 1049 fetuses. Regarding fetal imaging findings, the predictive value of the amniotic fluid was investigated by 15 articles, the renal appearance by 11, bladder findings by 4, and ureteral dilatation by 2. The postnatal renal function showed a statistically significant relationship with the occurrence of oligo- or anhydramnion in four studies, with an abnormal echogenic/cystic renal cortical appearance in three studies. Single articles proved the statistical prognostic value of the amniotic fluid index, the renal parenchymal area, the apparent diffusion coefficient (ADC) measured on fetal diffusion-weighted MRI, and the lower urinary tract obstruction (LUTO) stage (based on bladder volume at referral and gestational age at the appearance of oligo- or anhydramnios). Regarding the predictive value of fetal urinary analytes, sodium and ß2-microglobulin were the two most common urinary analytes investigated (n = 10 articles), followed by calcium (n = 6), chloride (n = 5), urinary osmolarity (n = 4), and total protein (n = 3). Phosphorus, glucose, creatinine, and urea were analyzed by two articles, and ammonium, potassium, N-Acetyl-l3-D-glucosaminidase, and microalbumin were investigated by one article. The majority of the studies (n = 8) failed to prove the prognostic value of fetal urinary analytes. However, two studies showed that a favorable urinary biochemistry profile (made up of sodium < 100 mg/dL; calcium < 8 mg/dL; osmolality < 200 mOsm/L; ß2-microglobulin < 4 mg/L; total protein < 20 mg/dL) could predict good postnatal renal outcomes with statistical significance and urinary levels of ß2-microglobulin were significantly higher in fetuses that developed an impaired renal function in childhood (10.9 ± 5.0 mg/L vs. 1.3 ± 0.2 mg/L, p-value < 0.05). Conclusions: Several demographic data, fetal imaging parameters, and urinary analytes have been shown to play a role in reliably triaging fetuses with megacystis for the risk of adverse postnatal renal outcomes. We believe that this systematic review can help clinicians for counseling parents on the prognoses of their infants and identifying the selected cases eligible for antenatal intervention.

Lung Function Evaluated By Structured Light Plethysmography in Children After Lung Surgery: A Preliminary Analysis.

Background: Structured light plethysmography (SLP) is a novel light-based method that captures chest wall movements to evaluate tidal breathing. Methods: Thirty-two children who underwent lung surgery were enrolled. Their clinical history was collected along with spirometry and SLP. Results: Median age of surgery was 9 months (interquartile range 4-30). Most frequent diagnosis was congenital pulmonary airway malformation (14/32), then pulmonary sequestration (9/32), tumor (5/32), and bronchogenic cyst (4/32). The most frequent surgical approach was lobectomy (59%), segmentectomy (38%), and complete resection (3%). More than 80% had surgery when younger than 3 years of age. Eight patients had short-term complications (pleural effusion was the most frequent), while long-term effects were reported in 15 patients (19% recurrent cough, 13% thoracic deformities, 13% airway infections, 9% wheezing, 6% reduced exercise tolerance, and 3% columnar deformities). Spirometry was normal in 9/22 patients. Nine patients had a restrictive pattern, while 4 showed a mild bronco-reactivity. Ten patients did not perform spirometry because of young age. SLP revealed the presence of obstructive pattern in 10% of patients (IE50 > 1.88) and showed a significant difference between the two hemithorax in 29% of patients. Discussion: SLP may be a new method to evaluate lung function, without collaboration and radiation exposure, in children who underwent lung resection, also in preschool age.

Congenital lung malformations: a nationwide survey on management aspects by the Italian Society of Pediatric Surgery.

INTRODUCTION: Over the years, congenital lung malformations (CLM) management remains a controversial topic in pediatric thoracic surgery. The Italian Society of Pediatric Surgery performed a national survey to study the current management variability among centers, trying to define national guidelines and a standardized approach of children with congenital lung malformations. METHODS: Following a National Society approval, an electronic survey including 35 items on post-natal management was designed, focusing on surgical, anesthesiology, radiology and pneumology aspects. The survey was conducted contacting all pediatric surgical units performing thoracic surgery. RESULTS: 39 pediatric surgery units (97.5%) participated in the study. 13 centers (33.3%) were classified as high-volume (Group A), while 26 centers (66.7%) were low volume (Group B). Variances in diagnostic imaging protocols were observed, with Group A performing fewer CT scans compared to Group B (p = 0.012). Surgical indications favored operative approaches for asymptomatic CLM and pulmonary sequestrations in both groups, while a wait-and-see approach was common for congenital lobar emphysema. Surgical timing for asymptomatic CLM differed significantly, with most high-volume centers operating on patients younger than 12 months (p = 0.02). Thoracoscopy was the preferred approach for asymptomatic CLM in most of centers, while postoperative long-term follow-up was not performed in most of the centers. CONCLUSION: Thoracoscopic approach seems uniform in asymptomatic CLM patients and variable in symptomatic children. Lack of uniformity in surgical timing and preoperative imaging assessment has been identified as key areas to establish a common national pattern of care for CLM.

Lung ultrasound-guided best positive end-expiratory pressure in neonatal anesthesia: a proposed randomized, controlled study.

BACKGROUND: Atelectasis is a common complication in neonatal anesthesia. Lung ultrasound (LUS) can be used intraoperatively to evaluate and recognize atelectatic lung areas. Hypotheses for the study are: (1) The use of LUS to guide choice of best positive end-expiratory pressure (PEEP) can lead to reduction of FiO2 to achieve same saturations of oxygen (SpO2). (2) In a less de-recruited lung, there will be less postoperative pulmonary complications. (3) Static respiratory system compliance could be different. (4) Hemodynamic parameters and amount of fluids infused or need for vasopressors intraoperatively could be different. METHODS: We propose a randomized controlled trial that compares standard PEEP settings with LUS-guided PEEP choice in patients under 2 months of age undergoing general anesthesia. RESULTS: The primary aim is to determine whether LUS-guided PEEP choice in neonatal anesthesia, compared to standard PEEP choice, can lead to reduction of FiO2 applied to the ventilatory setting in order to maintain same SpO2s. Secondary aims are to determine whether patients treated with LUS-guided PEEP will develop less postoperative pulmonary complications, will have a significant difference in hemodynamic parameters and amount of fluids or vasopressors infused, and in static respiratory system compliance. CONCLUSIONS: We expect a significant reduction of FiO2 in LUS-guided ventilation. IMPACT: Lung atelectasis is extremely common in neonatal anesthesia, because of the physiology of the neonatal lung and chest wall and leads to hypoxemia, being a lung area with a perfusion/ventilation mismatch. Raising inspired fraction of oxygen can overcome temporarily hypoxemia but oxygen is a toxic compound for newborns. Lung ultrasound (LUS) can detect atelectasis at bedside and be used to optimize ventilator settings including choice of positive end-expiratory pressure (PEEP). This randomized controlled trial (RCT) aims at demonstrating that LUS-guided choice of best PEEP during neonatal anesthesia can lead to reduction of inspired fractions of oxygen to keep same peripheral saturations SpO2.

Laparoscopic Cholecystectomy in Children: The Experience of Two Centers Focusing on Indications and Timing in the Era of "New Technologies".

BACKGROUND: In children, laparoscopic cholecystectomy (LC) is now considered the gold standard for gallbladder (GB) removal. In the past, hemolytic disorders associated with cholelithiasis represented the most frequent conditions requiring LC; this is being overtaken by cholelithiasis and biliary conditions in overweight or ex-premature children. AIMS: This study aims to describe current indications and timing for LC in pediatric patients. METHODS: Retrospective study. Data on previous medical therapy, ultrasound, pre- and intraoperative aspects, and histology were collected for patients treated in 2020-2023. RESULTS: In total, 45 patients were enrolled: 15 who underwent urgent surgery and 30 electives. Groups differed in terms of obesity rate, symptoms, ultrasound features, and intraoperative status. The most relevant risk factors for surgical complexity were age and pubertal stage, elevated cholestasis indexes, and gallbladder wall thickness > 3 mm at ultrasound. GB wall thickening ≥3 mm, US Murphy sign, fluid collections, and gallbladder distention on ultrasound correlated with high surgical scores. CONCLUSIONS: Indications for laparoscopic cholecystectomy in children seem to evolve caused by changing characteristics of the pediatric population. Patients with overweight/obesity may develop more complex GB diseases. Asymptomatic patients should be considered for surgery after observation, considering age and/or pubertal maturation when other risk factors are absent.

The treatment of obesity in children and adolescents: consensus position statement of the Italian society of pediatric endocrinology and diabetology, Italian Society of Pediatrics and Italian Society of Pediatric Surgery.

This Position Statement updates the different components of the therapy of obesity (lifestyle intervention, drugs, and surgery) in children and adolescents, previously reported in the consensus position statement on pediatric obesity of the Italian Society of Pediatric Endocrinology and Diabetology and the Italian Society of Pediatrics. Lifestyle intervention is the first step of treatment. In children older than 12 years, pharmacotherapy is the second step, and bariatric surgery is the third one, in selected cases. Novelties are available in the field of the medical treatment of obesity. In particular, new drugs demonstrated their efficacy and safety and have been approved in adolescents. Moreover, several randomized control trials with other drugs are in process and it is likely that some of them will become available in the future. The increase of the portfolio of treatment options for obesity in children and adolescents is promising for a more effective treatment of this disorder.

Bone Marrow Mesenchymal Stem Cells Expanded Inside the Nichoid Micro-Scaffold: a Focus on Anti-Inflammatory Response.

Purpose: Mesenchymal stem cells (MSCs) represent a promising source for stem cell therapies in numerous diseases, including pediatric respiratory system diseases. Characterized by low immunogenicity, high anti-inflammatory, and immunoregulatory features, MSCs demonstrated an excellent therapeutic profile in numerous in vitro and preclinical models. MSCs reside in a specialized physiologic microenvironment, characterized by a unique combination of biophysical, biochemical, and cellular properties. The exploitation of the 3D micro-scaffold Nichoid, which simulates the native niche, enhanced the anti-inflammatory potential of stem cells through mechanical stimulation only, overcoming the limitation of biochemical and xenogenic growth factors application. Materials and Methods: In this work, we expanded pediatric bone marrow MSCs (BM-MSCs) inside the Nichoid and performed a complete cellular characterization with different approaches including viability assays, immunofluorescence analyses, RNA sequencing, and gene expression analysis. Results: We demonstrated that BM-MSCs inside the scaffold remain in a stem cell quiescent state mimicking the condition of the in vivo environment. Moreover, the gene expression profile of these cells shows a significant up-regulation of genes involved in immune response when compared with the flat control. Conclusion: The significant changes in the expression profile of anti-inflammatory genes could potentiate the therapeutic effect of BM-MSCs, encouraging the possible clinical translation for the treatment of pediatric congenital and acquired pulmonary disorders, including post-COVID lung manifestations. Lay Summary: Regenerative medicine is the research field integrating medicine, biology, and biomedical engineering. In this context, stem cells, which are a fundamental cell source able to regenerate tissues and restore damage in the body, are the key component for a regenerative therapeutic approach. When expanded outside the body, stem cells tend to differentiate spontaneously and lose regenerative potential due to external stimuli. For this reason, we exploit the scaffold named Nichoid, which mimics the in vivo cell niche architecture. In this scaffold, mesenchymal stem cells "feel at home" due to the three-dimensional mechanical stimuli, and our findings could be considered as an innovative culture system for the in vitro expansion of stem cells for clinical translation. Future Perspective: The increasing demand of safe and effective cell therapies projects our findings toward the possibility of improving cell therapies based on the use of BM-MSCs, particularly for their clinical translation in lung diseases.

Echo-Endoscopy Combined with Virtual Reality: A Whole Perspective of Laparoscopic Common Bile Duct Exploration in Children.

Introduction: Endoscopic procedures are performed more frequently in children due to technological advances that can be safely performed in an adequate setting with a support of a multidisciplinary team. Pediatric indications for ERCP (endoscopic retrograde cholangiopancreatography) and EUS (endoscopic ultrasound) occur mainly due to congenital malformations. In a pediatric case series, we report the application of EUS combined with duodenoscopy, eventually associated with ERCP and minimally invasive surgery, highlighting the importance of defining a tailored dedicated management pathway for each patient. Patients and methods: A series of 12 patients, managed at our Center in the last three years, were evaluated, and their management was discussed. Results: EUS was performed in eight patients and permitted the differential diagnosis of duplication cysts and the visualization of the biliary tree and pancreatic anatomy. ERCP was attempted in five patients: in one case, it permitted the preservation of pancreatic tissue, postponing surgery and in three patients, it was technically unfeasible. MIS (minimally invasive surgery) was performed in seven patients, two with laparoscopic common bile duct exploration (LCBDE). Precise anatomical definition and the possibility of surgical simulation and team sharing were evaluated under VR HMD (Virtual Reality Head Mounted Display) in four cases. Conclusions: Exploration of the common bile duct in children differs from that of the adult population and combines echo-endoscopy and ERCP. The integrated use of minimally invasive surgery in the pediatric area is necessary for the whole management perspective in complex malformations and small patients. The introduction in the clinical practice of a preoperative study with Virtual Reality allows a better survey of the malformation and a tailored treatment.

Subcutaneous Adipose Tissue Transcriptome Highlights Specific Expression Profiles in Severe Pediatric Obesity: A Pilot Study.

The prevalence of pediatric obesity is rising rapidly worldwide, and "omic" approaches are helpful in investigating the molecular pathophysiology of obesity. This work aims to identify transcriptional differences in the subcutaneous adipose tissue (scAT) of children with overweight (OW), obesity (OB), or severe obesity (SV) compared with those of normal weight (NW). Periumbilical scAT biopsies were collected from 20 male children aged 1-12 years. The children were stratified into the following four groups according to their BMI z-scores: SV, OB, OW, and NW. scAT RNA-Seq analyses were performed, and a differential expression analysis was conducted using the DESeq2 R package. A pathways analysis was performed to gain biological insights into gene expression. Our data highlight the significant deregulation in both coding and non-coding transcripts in the SV group when compared with the NW, OW, and OB groups. A KEGG pathway analysis showed that coding transcripts were mainly involved in lipid metabolism. A GSEA analysis revealed the upregulation of lipid degradation and metabolism in SV vs. OB and SV vs. OW. Bioenergetic processes and the catabolism of branched-chain amino acids were upregulated in SV compared with OB, OW, and NW. In conclusion, we report for the first time that a significant transcriptional deregulation occurs in the periumbilical scAT of children with severe obesity compared with those of normal weight or those with overweight or mild obesity.

Congenital diaphragmatic hernia increases the sensitivity of pulmonary arteries to nitric oxide.

Left congenital diaphragmatic hernia (CDH) can lead to pulmonary arteries abnormalities in the contralateral and ipsilateral sides of the diaphragm. Nitric oxide (NO) is the main therapy used to attenuate the vascular effects of CDH, but it is not always effective. We hypothesized that the left and right pulmonary arteries do not respond similarly to NO donors during CDH. Therefore, vasorelaxant responses of the left and right pulmonary arteries to sodium nitroprusside (SNP, a NO donor) were determined in a rabbit experimental model of left CDH. CDH was surgically induced in the fetuses of rabbits on the 25th day of pregnancy. On the 30th day of pregnancy, a midline laparotomy was performed to access the fetuses. The fetuses' left and right pulmonary arteries were isolated and mounted in myograph chambers. Vasodilation was evaluated by cumulative concentration-effect curves to SNP. Protein expression of guanylate cyclase isoforms (GCα, GCß) and the α isoform of cGMP-dependent protein kinase 1 (PKG1α), and the concentration of NO and cGMP were determined in the pulmonary arteries. The left and right pulmonary arteries of newborns with CDH exhibited increased vasorelaxant responses to SNP (i.e. the potency of SNP was increased) compared to the control group. GCα, GCß, and PKG1α expression were decreased, while NO and cGMP concentrations were increased in the pulmonary arteries of newborns with CDH compared to the control group. The increased cGMP mobilization may be responsible for the increased vasorelaxant responses to the SNP in the pulmonary arteries during left CDH.