Myocardial dysfunction and resulting low cardiac output syndrome (LCOS) contribute significantly to postoperative morbidity and mortality in pediatric heart surgery. Despite major advances in diagnostic accuracy and intra-operative myocardial protection strategies, LCOS remains an important clinical problem with an estimated incidence of ~25% in infants undergoing cardiopulmonary bypass. This application proposes a multi-center, randomized, double blind, placebo-controlled clinical trial, to investigate whether preoperative administration of glucocorticoids (methylprednisolone, steroids) and/or erythropoietin (EPO) will afford protection from ischemia-reperfusion injury and thereby reduce the incidence of LCOS for infants undergoing cardiopulmonary bypass. Furthermore, although there are important interactions between these two agents, the primary signaling pathways are distinct;hence, combined use may result in a synergistic reduction in the incidence of LCOS. There will be four preoperative treatment arms: 1) placebo;2) steroids;3) EPO;and 4) steroids and EPO combined. The study design assumes that intra-operative steroids will be administered. This assumption is based on a recent published survey documenting this as common practice in pediatric centers, and our own investigations that demonstrate an improved benefit from pre- and intraoperative steroid use. The Primary Aim of the proposed study is to compare the effect of preoperative steroids and/or EPO with placebo on LCOS incidence through the first 48 hours following cardiopulmonary bypass surgery. Hypotheses to be tested include: 1) Preoperative steroids protect against ischemia-reperfusion injury to enhance myocardial performance postoperatively, resulting in a lower incidence of LCOS. 2) Preoperative EPO protects cardiomyocytes during ischemia-reperfusion, resulting in improved myocardial performance postoperatively with a subsequent reduction in the incidence of LCOS. 3) Concurrent administration of preoperative steroids and EPO will have a synergistic effect to reduce the incidence of LCOS. The Primary Outcome is LCOS. The diagnosis of LCOS will be based on a composite of clinical signs and symptoms, biochemical markers, and the need for additional inotropic/mechanical support. Five Secondary Aims will assess treatment effects on mortality and clinical measures of morbidity, postoperative myocardial performance, inflammatory and non-inflammatory mediators of myocardial dysfunction pre- and post-heart surgery, cardiomyocyte protection and apoptosis pre- and post-cardiopulmonary bypass surgery and the incidence of renal injury within 48 hours after cardiopulmonary bypass surgery. Completion of the proposed studies should greatly improve our understanding of ischemia-reperfusion injury and therapies to prevent LCOS following surgery with cardiopulmonary bypass in infants.
| Newburger, Jane W; Sleeper, Lynn A; Gaynor, J William et al. (2018) Transplant-Free Survival and Interventions at 6 Years in the SVR Trial. Circulation 137:2246-2253 |
| Hoskoppal, Arvind; Menon, Shaji; Trachtenberg, Felicia et al. (2018) Predictors of Rapid Aortic Root Dilation and Referral for Aortic Surgery in Marfan Syndrome. Pediatr Cardiol 39:1453-1461 |
| Mahle, William T; Hu, Chenwei; Trachtenberg, Felicia et al. (2018) Heart failure after the Norwood procedure: An analysis of the Single Ventricle Reconstruction Trial. J Heart Lung Transplant 37:879-885 |
| Selamet Tierney, Elif Seda; Levine, Jami C; Sleeper, Lynn A et al. (2018) Influence of Aortic Stiffness on Aortic-Root Growth Rate and Outcome in Patients With the Marfan Syndrome. Am J Cardiol 121:1094-1101 |
| Mussatto, Kathleen A; Hollenbeck-Pringle, Danielle; Trachtenberg, Felicia et al. (2018) Utilisation of early intervention services in young children with hypoplastic left heart syndrome. Cardiol Young 28:126-133 |
| Oster, Matthew E; Chen, Shan; Dagincourt, Nicholas et al. (2017) Development and impact of arrhythmias after the Norwood procedure: A report from the Pediatric Heart Network. J Thorac Cardiovasc Surg 153:638-645.e2 |
| Margossian, Renee; Zak, Victor; Shillingford, Amanda J et al. (2017) The Effect of the Superior Cavopulmonary Anastomosis on Ventricular Remodeling in Infants with Single Ventricle. J Am Soc Echocardiogr 30:699-707.e1 |
| Ramroop, Ronand; Manase, George; Lu, Danny et al. (2017) Adrenergic receptor genotypes influence postoperative outcomes in infants in the Single-Ventricle Reconstruction Trial. J Thorac Cardiovasc Surg 154:1703-1710.e3 |
| Burch, Phillip T; Ravishankar, Chitra; Newburger, Jane W et al. (2017) Assessment of Growth 6 Years after the Norwood Procedure. J Pediatr 180:270-274.e6 |
| Lambert, Linda M; Trachtenberg, Felicia L; Pemberton, Victoria L et al. (2017) Passive range of motion exercise to enhance growth in infants following the Norwood procedure: a safety and feasibility trial. Cardiol Young 27:1361-1368 |
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