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Robust preclinical models of asymmetric ventricular loading in late gestation reflecting conditions such as hypoplastic left heart syndrome are lacking. We characterized the morphometry and microvascular function of the hypoplastic left ventricle (LV) and remaining right ventricle (RV) in a sham-controlled late gestation fetal lamb model of impaired left ventricular inflow (ILVI). Singleton fetuses were instrumented at ∼120 days gestational age (dGA; term is ∼147 days) with vascular catheters, an aortic flow probe and a deflated left atrial balloon. Balloons in ILVI fetuses were inflated over the 8 day study until aortic output was eliminated; Sham balloons remained deflated. At the study end-point (∼134 dGA), cardiac function was assessed by echocardiography, microvascular perfusion of each free wall was measured by myocardial contrast echocardiography (MCE) and terminal morphometric data were collected. During the chronic study, flow through the ascending aorta of ILVI fetuses fell from 389 to -48 mL min -1 with minimal changes to other haemodynamics or blood chemistry. End-point echocardiography and morphometry similarly showed significant and meaningful reductions in ILVI LV chamber volume and wall mass without statistically significant changes in RV size relative to Shams. MCE revealed modestly increased LV perfusion and profoundly increased RV perfusion in ILVI fetuses. Our model displays effective LV hypoplasia with preserved overall fetal health, and our finding of increased RV myocardial perfusion may indicate active vascular remodelling in response to the experimental lesion. KEY POINTS: Hypoplastic left heart syndrome can be caused by insufficient inflow of blood to the fetal left ventricle. We found that eliminating fetal left ventricular input for 8 days reduced left ventricular size and volume, with minimal effects on the right ventricle or overall fetal health. Blood and oxygen delivery increased significantly in the right ventricle and slightly in the hypoplastic left ventricle. Our results suggest functional and anatomical adaptation of the fetal coronary microvasculature to univentricular right heart conditions., (© 2025 The Authors. The Journal of Physiology © 2025 The Physiological Society.)

Background: Dysregulated nitric oxide (NO) signaling contributes to chronic hypoxia (CH)-induced pulmonary hypertension (PH). NO signaling is improved and pulmonary vascular resistance (PVR) is reduced in CH piglets treated with the l-arginine-NO precursor, l-citrulline. We hypothesized that l-citrulline might cause structural changes in the pulmonary circulation that would contribute to the reduction in PVR and that the l-citrulline-induced structural changes would be accompanied by alterations in vascular endothelial growth factor (VEGF) signaling., Methods: We evaluated small pulmonary arterial (PA) wall thickness, lung capillary density, and protein abundances of VEGF, VEGFR2, and phospho (p)-VEGFR2 in PA and peripheral lung samples of piglets raised in the lab in CH (10%-12% O 2 ) from the day of life (DOL) 2 until DOL 11 to 12 or raised in room air (normoxia) by the vendor and studied on arrival to the lab on DOL 11 to 12. Some CH piglets were treated with oral l-citrulline (1-1.5 g/kg/d) starting on the third day of hypoxia., Results: PA wall thickness was 32% less and lung capillary formation was nearly doubled in l-citrulline treated than untreated CH piglets. Both of these l-citrulline-induced structural changes in the pulmonary circulation were accompanied by altered amounts of VEGF protein but not by altered amounts of either VEGFR2 or p-VEGFR2 proteins., Conclusions: Alterations in the structure of the pulmonary circulation in CH piglets by l-citrulline are unlikely to be mediated by overall VEGF signaling. Nonetheless, l-citrulline- induced structural changes should reduce PVR and thereby contribute to the amelioration of CH-induced PH., (© 2020 Wiley Periodicals LLC.)

Trauma patients admitted without vital signs have little hope of survival even with extreme interventions. We performed this study to determine the effect of age on survival in patients in extremis undergoing urgent thoracotomy. The National Trauma Database was searched for patients presenting without a systolic blood pressure (0), a Glasgow Coma Scale score less than 8, and underwent an urgent thoracotomy. Mortality was determined for pediatric (younger than 16 years) and older patients (older than 60 years) and compared. Of 708 patients, 32 (4.5%) were pediatric and 57 (8.1%) were elderly. Pediatric mortality was 93.8 per cent (30) versus 95.6 per cent (646) for patients older than 16 years (P = 0.981). Mortality in the older patients was 94.7 per cent (54) versus 95.5 per cent (622) in patients younger than 60 years (P = 0.778). Race and blunt injury were independently associated with death. However, neither pediatric (P = 0.418) nor older status (P = 0.184) was predictive. Age does not significantly impact mortality in patients in extremis who undergo urgent thoracotomy. Age should not be a contributing factor in determining who should undergo more extreme maneuvers if they present as a reasonable candidate using other criteria.

Purpose: Liver herniation is a rare occurrence in gastroschisis. We sought to determine the incidence and prognosis of liver herniation in patients with gastroschisis., Methods: From December 1995 to March 2010, 117 patients with gastroschisis received care by our division. Operative reports were reviewed to identify patients with liver herniation. Logistic regression was used to determine the impact of liver herniation on survival, taking into account gestational age and birth weight., Results: The incidence of liver herniation was 6%. Survival rates were 43% with liver herniation and 97% without liver herniation. Liver herniation was associated with a significantly higher rate of mortality, taking into account estimated gestational age and birth weight (P < .001). Patients who had liver herniation documented by prenatal ultrasound had significant liver herniation at birth and died postnatally. Patients with liver herniation who died required large silos and were noted to have comorbidities including lower birth weight, pulmonary hypoplasia, and sepsis. Biologic patches were necessary for closure in patients with greater extent of liver herniation., Conclusions: Liver herniation was found in 6% of patients with gastroschisis and was associated with a high rate of mortality. Liver herniation appears to be a risk factor for poor outcome in gastroschisis. Documentation of liver herniation may be helpful in prenatal consultation for gastroschisis., (Copyright © 2011 Elsevier Inc. All rights reserved.)