Xenogeneic pericardium-based substitutes are employed for several surgical indications after chemical shielding, limiting their biocompatibility and therapeutic durability. Adverse responses to these replacements might be prevented by tissue decellularization, ideally removing cells and preserving the original extracellular matrix (ECM). The aim of this study was to compare the mostly applied pericardia in clinics, i.e., bovine and porcine tissues, after their decellularization, and obtain new insights for their possible surgical use. Bovine and porcine pericardia were submitted to TRICOL decellularization, based on osmotic shock, detergents and nuclease treatment. TRICOL procedure resulted in being effective in cell removal and preservation of ECM architecture of both species’ scaffolds. Collagen and elastin were retained but glycosaminoglycans were reduced, significantly for bovine scaffolds. Tissue hydration was varied by decellularization, with a rise for bovine pericardia and a decrease for porcine ones. TRICOL significantly increased porcine pericardial thickness, while a non-significant reduction was observed for the bovine counterpart. The protein secondary structure and thermal denaturation profile of both species’ scaffolds were unaltered. Both pericardial tissues showed augmented biomechanical compliance after decellularization. The ECM bioactivity of bovine and porcine pericardia was unaffected by decellularization, sustaining viability and proliferation of human mesenchymal stem cells and endothelial cells. In conclusion, decellularized bovine and porcine pericardia demonstrate possessing the characteristics that are suitable for the creation of novel scaffolds for reconstruction or replacement: differences in water content, thickness and glycosaminoglycans might influence some of their biomechanical properties and, hence, their indication for surgical use.

Urinary acidification in the collecting duct is mediated by the activity of H⁺-ATPases and is stimulated by various factors including angiotensin II and aldosterone. Classically, aldosterone effects are mediated via the mineralocorticoid receptor. Recently, we demonstrated a nongenomic stimulatory effect of aldosterone on H⁺-ATPase activity in acid-secretory intercalated cells of isolated mouse outer medullary collecting ducts (OMCD). Here we investigated the intracellular signaling cascade mediating this stimulatory effect. Aldosterone stimulated H⁺-ATPase activity in isolated mouse and human OMCDs. This effect was blocked by suramin, a general G protein inhibitor, and GP-2A, a specific G_αqinhibitor, whereas pertussis toxin was without effect. Inhibition of phospholipase C with U-73122, chelation of intracellular Ca²⁺with BAPTA, and blockade of protein kinase C prevented the stimulation of H⁺-ATPases. Stimulation of PKC by DOG mimicked the effect of aldosterone on H⁺-ATPase activity. Similarly, aldosterone and DOG induced a rapid translocation of H⁺-ATPases to the luminal side of OMCD cells in vivo. In addition, PD098059, an inhibitor of ERK1/2 activation, blocked the aldosterone and DOG effects. Inhibition of PKA with H89 or KT2750 prevented and incubation with 8-bromoadenosine-cAMP mildly increased H⁺-ATPase activity. Thus, the nongenomic modulation of H⁺-ATPase activity in OMCD-intercalated cells by aldosterone involves several intracellular pathways and may be mediated by a G_αqprotein-coupled receptor and PKC. PKA and cAMP appear to have a modulatory effect. The rapid nongenomic action of aldosterone may participate in the regulation of H⁺-ATPase activity and contribute to final urinary acidification.

Background. Data on long-term outcomes in the era before therapeutic hypothermia (TH) showed a higher incidence of cognitive problems. Since the introduction of TH, data on its results are limited. Methods. Our sample population consisted of 40 children with a history of hypoxic-ischemic encephalopathy (HIE) treated with TH, with an average age of 6.25 years (range 5.5, 7.33), 24 (60%) males; and 33 peers with an average age of 8.8 years (6.08, 9.41), 17 (51%) males. Long-term follow-up data belong to two centers in Padova and Torino. We measured general intelligence (WPPSI-III or WISC-IV) and neuropsychological functioning (language, attention, memory, executive functions, social skills, visual motor abilities). We also administered questionnaires to their parents on the children’s psychopathological profiles and parental stress. Results. We found differences between groups in several cognitive and neuropsychological domains: intelligence, visuomotor skills, executive functions, and attention. Interestingly, IQ test results effectively differentiated between the groups (HIE vs. controls). Furthermore, the incidence of psychopathology appears to be significantly higher in children with HIE (35%) than in control peers (12%). Conclusions. Our study supports previous findings on a higher incidence of neuropsychological, cognitive, and psychopathological sequelae after HIE treated with TH. As hypothesized, TH does not appear to ameliorate the outcome after neonatal HIE in those children who survive without major sequelae.

OBJECTIVES: We sought to describe early and late outcomes in a large surgical series of patients with anomalous aortic origin of coronary arteries. METHODS: We performed a retrospective multicentre study including surgical patients with anomalous aortic origin of coronary arteries since 1991. Patients with isolated high coronary takeoff and associated major congenital heart disease were excluded. RESULTS: We collected 156 surgical patients (median age 39.5 years, interquartile range 15–53) affected by anomalous right (67.9%), anomalous left (22.4%) and other anatomical abnormalities (9.6%). An interarterial course occurred in 86.5%, an intramural course in 62.8% and symptoms in 85.9%. The operations included coronary unroofing (56.4%), reimplantation (19.2%), coronary bypass graft (15.4%) and other (9.0%). Two patients with preoperative cardiac failure died postoperatively (1.3%). All survivors were discharged home in good clinical condition. At a median follow-up of 2 years (interquartile range 1–5, 88.5% complete), there were 3 deaths (2.2%), 9 reinterventions in 8 patients (5 interventional, 3 surgical); 91.2% are in New York Heart Association functional class ≤ II, but symptoms persisted in 14.2%; 48.1% of them returned to sport activity. On Kaplan–Meier analysis, event-free survival at follow-up was 74.6%. Morbidity was not significantly different among age classes, anatomical variants and types of surgical procedures. Furthermore, return to sport activity was significantly higher in younger patients who participated in sports preoperatively. CONCLUSIONS: Surgical repair of anomalous aortic origin of coronary arteries is effective and has few complications. Unroofing and coronary reimplantation are safe and are the most common procedures. The occurrence of late adverse events is not negligible, and long-term surveillance is mandatory. Most young athletes can return to an unrestrained lifestyle.