Progression Toward Decompensated Right Ventricular Failure in the Ovine Pulmonary Hypertension Model.

Decompensated right ventricular failure (RVF) in patients with pulmonary hypertension (PH) is fatal, with limited treatment options. Novel mechanical circulatory support systems have therapeutic potential for RVF, but the development of these devices requires a large animal disease model that replicates the pathophysiology observed in humans. We previously reported an effective disease model of PH in sheep through ligation of the left pulmonary artery (PA) and progressive occlusion of the main PA. Herein, we report a case of acute decompensation with this model of chronic RVF. Gradual PA banding raised the RV pressure (maximum RV systolic/mean pressure = 95 mmHg/56 mmHg). Clinical findings and laboratory serum parameters suggested appropriate physiologic compensation for 7 weeks. However, mixed venous saturation declined precipitously on week 7, and creatinine increased markedly on week 9. By the 10th week, the animal developed dependent, subcutaneous edema. Subsequently, the animal expired during the induction of general anesthesia. Post-mortem evaluation revealed several liters of pleural effusion and ascites, RV dilatation, eccentric RV hypertrophy, and myocardial fibrosis. The presented case supports this model's relevance to the human pathophysiology of RVF secondary to PH and its value in the development of novel devices, therapeutics, and interventions.

Cross-Circulation for Extracorporeal Liver Support in a Swine Model.

Although machine perfusion has gained momentum as an organ preservation technique in liver transplantation, persistent organ shortages and high waitlist mortality highlight unmet needs for improved organ salvage strategies. Beyond preservation, extracorporeal organ support platforms can also aid the development and evaluation of novel therapeutics. Here, we report the use of veno-arterial-venous (V-AV) cross-circulation (XC) with a swine host to provide normothermic support to extracorporeal livers. Functional, biochemical, and morphological analyses of the extracorporeal livers and swine hosts were performed over 12 hours of support. Extracorporeal livers maintained synthetic function through alkaline bile production and metabolic activity through lactate clearance and oxygen consumption. Beyond initial reperfusion, no biochemical evidence of hepatocellular injury was observed. Histopathologic injury scoring showed improvements in sinusoidal dilatation and composite acute injury scores after 12 hours. Swine hosts remained hemodynamically stable throughout XC support. Altogether, these outcomes demonstrate the feasibility of using a novel V-AV XC technique to provide support for extracorporeal livers in a swine model. V-AV XC has potential applications as a translational research platform and clinical biotechnology for donor organ salvage.

Left Pulmonary Artery Ligation and Chronic Pulmonary Artery Banding Model for Inducing Right Ventricular-Pulmonary Hypertension in Sheep.

Pulmonary hypertension (PH) is a progressive disease that leads to cardiopulmonary dysfunction and right heart failure from pressure and volume overloading of the right ventricle (RV). Mechanical cardiopulmonary support has theoretical promise as a bridge to organ transplant or destination therapy for these patients. Solving the challenges of mechanical cardiopulmonary support for PH and RV failure requires its testing in a physiologically relevant animal model. Previous PH models in large animals have used pulmonary bead embolization, which elicits unpredictable inflammatory responses and has a high mortality rate. We describe a step-by-step guide for inducing pulmonary hypertension and right ventricular hypertrophy (PH-RVH) in sheep by left pulmonary artery (LPA) ligation combined with progressive main pulmonary artery (MPA) banding. This approach provides a controlled method to regulate RV afterload as tolerated by the animal to achieve PH-RVH, while reducing acute mortality. This animal model can facilitate evaluation of mechanical support devices for PH and RV failure.

Xenogeneic cross-circulation for extracorporeal recovery of injured human lungs.

Patients awaiting lung transplantation face high wait-list mortality, as injury precludes the use of most donor lungs. Although ex vivo lung perfusion (EVLP) is able to recover marginal quality donor lungs, extension of normothermic support beyond 6 h has been challenging. Here we demonstrate that acutely injured human lungs declined for transplantation, including a lung that failed to recover on EVLP, can be recovered by cross-circulation of whole blood between explanted human lungs and a Yorkshire swine. This xenogeneic platform provided explanted human lungs a supportive, physiologic milieu and systemic regulation that resulted in functional and histological recovery after 24 h of normothermic support. Our findings suggest that cross-circulation can serve as a complementary approach to clinical EVLP to recover injured donor lungs that could not otherwise be utilized for transplantation, as well as a translational research platform for immunomodulation and advanced organ bioengineering.

Impaired growth outcomes in children with congenital colorectal diseases.

BACKGROUND: Cloaca, Hirschsprung disease, and anorectal malformations (CHARM) are congenital anomalies of the hindgut. Small series have suggested that children suffering from one of these anomalies may be at risk for growth impairment. We sought to expand on these findings in a comprehensive cohort, hypothesizing that patients with Medicaid insurance or African-American (AA) race would be at higher risk for poor growth. METHODS: Following Institutional Review Board (IRB) approval, single-institution retrospective review of children with CHARM anomalies was performed (2009-2016). Body mass index (BMI) value Z-scores were obtained using the 2006 World Health Organization (age 0-24 mo) and 2000 Centers for Disease Control (CDC) (age >2 y) growth charts and calculators (statistical analysis system). Patient factors and BMI Z-scores were analyzed with descriptive statistics and Fisher's exact test. RESULTS: One hundred sixty-six patients (Cloaca n = 16, Hirschsprung disease [HD] n = 71, anorectal malformation [ARM] n = 79) were identified. The BMI Z-score distribution for the entire CHARM cohort was lower than controls (P < 0.0001). HD and ARM BMI Z-scores were also lower versus controls (P < 0.0007, P < 0.0037). Requiring more or less than the average number of surgeries did not impact BMI Z-score [P = non-significant (NS)]. Patients with Medicaid had lower Z-scores versus private or commercial insurance (P < 0.0001). AA race BMI Z-score distribution was lower than controls (P < 0.0002), but there was no statistical difference in BMI Z-scores when comparing AA versus non-AA CHARM patients (P = NS). CONCLUSIONS: Patients born with CHARM anomalies are at risk for impaired growth. Furthermore study is warranted to identify modifiable risk factors contributing to this impairment. Longitudinal follow-up should include interventions to mitigate these risks.

Neonatal Perforated Appendicitis Attributed to Localized Necrotizing Enterocolitis of the Appendix: A Review.

Neonatal appendicitis is a rare clinical entity associated with remarkable morbidity and mortality. Appendicular perforation is common and the diagnosis is usually made intra-operatively. The causative etiology of neonatal perforated appendicitis (NPA) is a subject of debate and has not been elucidated. Although many etiologic theories exist, increasing evidence suggests a subset of NPA cases may represent a form of necrotizing enterocolitis (NEC) localized to the appendix. We herein present a review of the current literature to include cases of NPA attributed to localized NEC. A high index of clinical suspicion and early laparotomy are recommended.

Neonatal Perforated Appendicitis Masquerading as Necrotizing Enterocolitis.

A preterm neonate underwent emergent laparotomy for presumed necrotizing enterocolitis (NEC). Intra-operatively, neonatal perforated appendicitis (NPA) was encountered. This may represent a form of NEC localized to the appendix. A high index of clinical suspicion and early laparotomy are recommended.