Acute kidney injury (AKI) is associated with prolonged hospitalization and mortality following infant cardiac surgery, but therapeutic options are limited. Alkaline phosphatase (AP) infusion reduced AKI in phase 2 sepsis trials but has not been evaluated for cardiac surgery-induced AKI. We developed a porcine model of infant cardiopulmonary bypass (CPB) with deep hypothermic circulatory arrest (DHCA) to investigate post-CPB/DHCA AKI, measure serum/renal tissue AP activity with escalating doses of AP infusion, and provide preliminary assessment of AP infusion for prevention of AKI. Infant pigs underwent CPB with DHCA followed by survival for 4 h. Groups were treated with escalating doses of bovine intestinal AP (1, 5, or 25U/kg/hr). Anesthesia controls were mechanically ventilated for 7 h without CPB. CPB/DHCA animals demonstrated histologic and biomarker evidence of AKI as well as decreased serum and renal tissue AP compared to anesthesia controls. Only high dose AP infusion significantly increased serum or renal tissue AP activity. Preliminary efficacy evaluation demonstrated a trend towards decreased AKI in the high dose AP group. The results of this dose-finding study indicate that AP infusion at the dose of 25U/kg/hr corrects serum and tissue AP deficiency and may prevent AKI in this piglet model of infant CPB/DHCA.
Background: Expectations towards surgeons in modern surgical practice are extremely high with minimal complication rates and maximal patient safety as paramount objectives. Both of these aims are highly dependent on individual technical skills that require sustained, focused, and efficient training outside the clinical environment. At the same time, there is an increasing moral and ethical pressure to reduce the use of animals in research and training, which has fundamentally changed the practice of microsurgical training and research. Various animal models were introduced and widely used during the mid-20th century, the pioneering era of experimental microsurgery. Since then, high numbers of ex vivo training concepts and quality control measures have been proposed, all aiming to reduce the number of animals without compromising quality and outcome of training. Summary: Numerous microsurgical training courses are available worldwide, but there is no general agreement concerning the standardization of microsurgical training. The major aim of this literature review and recommendation is to give an overview of various aspects of microsurgical training. We introduce here the findings of a previous survey-based analysis of microsurgical courses within our network. Basic principles behind microsurgical training (3Rs, good laboratory practice, 3Cs), considerations around various microsurgical training models, as well as several skill assessment tools are discussed. Recommendations are formulated following intense discussions within the European Society for Surgical Research (ESSR) and the International Society for Experimental Microsurgery (ISEM), based on scientific literature as well as on several decades of experience in the field of experimental (micro)surgery and preclinical research, represented by the contributing authors. Key Messages: Although ex vivo models are crucial for the replacement and reduction of live animal use, living animals are still indispensable at every level of training which aims at more than just a basic introduction to microsurgical techniques. Modern, competency-based microsurgical training is multi-level, implementing different objective assessment tools as outcome measures. A clear consensus on fundamental principles of microsurgical training and more active international collaboration for the sake of standardization are urgently needed.
The intestinal microbiome is essential to human health and homeostasis and is implicated in the pathophysiology of disease, including congenital heart disease and cardiac surgery. Improving the microbiome and reducing inflammatory metabolites may reduce systemic inflammation following cardiac surgery with cardiopulmonary bypass (CPB) to expedite recovery post-operatively. Limited research exists in this area and identifying animal models that can replicate changes in the human intestinal microbiome after CPB are necessary. We used a piglet model of CPB with 2 groups, CPB (n=5) and a control group with mechanical ventilation (n=7) to evaluate changes to the microbiome, intestinal barrier dysfunction, and intestinal metabolites with inflammation after CPB. We identified significant changes to the microbiome, barrier dysfunction, intestinal short chain fatty acids and eicosanoids, and elevate cytokines in the CPB/DHCA group compared to the control group at just four hours after intervention. This piglet model of CPB replicates known human changes to the intestinal flora and metabolite profile and can be used to evaluate gut interventions aimed at reducing downstream inflammation after cardiac surgery with CPB.
Infants with CHD are at increased risk of necrotising enterocolitis, which can interfere with the achievement of adequate nutrition and, ultimately, growth and development. Necrotising enterocolitis is classified by severity as suspected, confirmed, and advanced. We sought to quantify the incidence of all types of necrotising enterocolitis among infants who underwent surgery, with a particular focus on suspected necrotising enterocolitis. This is a retrospective review of all infants <6 months of age who underwent cardiac surgery during 2012 and 2013 at Children's Hospital Colorado. We examined the hospital course of 265 hospitalisations (n=251 patients) and found 18 patients (19 hospitalisations) with suspected necrotising enterocolitis and 16 patients (16 hospitalisations) with confirmed or advanced necrotising enterocolitis. Single-ventricle physiology, lower weight, and younger age were associated with necrotising enterocolitis. Patients with all types of necrotising enterocolitis experienced prolonged length of hospital stay. We found suspected necrotising enterocolitis to be as common as confirmed necrotising enterocolitis, and it frequently occurred early in the post-operative course. We speculate that suspected necrotising enterocolitis may often be overlooked in research owing to a reliance on billing codes. Nevertheless, suspected necrotising enterocolitis poses a substantial barrier to post-operative progression of the CHD patient, as does confirmed necrotising enterocolitis. Following the diagnosis of all types of necrotising enterocolitis, there was wide variability in practice patterns. In response to this variability, we developed care guidelines for the diagnosis and treatment of necrotising enterocolitis in this population.
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