1) Alkaline phosphatase in infant cardiopulmonary bypass: In 2012 our group identified an unexpected finding of markedly decreased alkaline phosphatase activity immediately following cardiothoracic surgery in infants with congenital heart disease. Lower alkaline phosphatase activity was strongly associated with increased intensity and duration of post-operative support. Given recent studies demonstrating potential novel protective effects of alkaline phosphatase such as dephosphorylation of endotoxin and extracellular adenine nucleotides, we became intrigued about alkaline phosphatase as a potential therapy to prevent intestinal and kidney injury following cardiac surgery in our high risk patients with congenital heart disease. I was awarded a K23 grant from the NIH/NHLBI to further assess alkaline phosphatase as a biomarker in this population as well as a potential therapeutic target to aid in clearance of harmful extracellular adenine nucleotides and endotoxin. I have also recently developed a large animal model of infant cardiopulmonary bypass and deep hypothermic circulatory arrest funded by the American Heart Association and Department of Defense in order to both test novel therapeutics (including alkaline phosphatase) as well as to study the mechanisms of post-operative multi-organ injury.
a. Jesse A. Davidson, Tracy Urban, Suhong Tong, Mark Twite, Alan Woodruff, Paul E. Wischmeyer, Jelena Klawitter. Alkaline phosphatase, soluble extracellular adenine nucleotides, and adenosine production after infant cardiopulmonary bypass. PLOS One 2016; 1-15.
b. Jesse Davidson, Tracy Urban, Suhong Tong, Christine Baird, Mark Twite, James Jaggers, Eric Simoes, Paul Wischmeyer. Alkaline phosphatase in infant cardiopulmonary bypass: kinetics and relationship to organ injury and major cardiovascular events. Journal of Pediatrics 2017 Nov; 109:49-55.
c. Jesse A. Davidson, Tracy T. Urban, Suhong Tong, Aline Maddux, Gerald Hill, Benjamin S. Frank, John D. Watson, James Jaggers, Eric A. F. Simões, Paul Wischmeyer. Alkaline Phosphatase Activity and Endotoxemia after Infant Cardiothoracic Surgery. Shock 2019; 51(3), 328-336.
d. Jesse A. Davidson, Ludmila Khailova, Amy Treece, Justin Robison, Danielle E. Soranno, James Jaggers, Richard J. Ing, Scott Lawson, Suzanne Osorio Lujan. Alkaline Phosphatase Treatment of Acute Kidney Injury in an Infant Piglet Model of Cardiopulmonary Bypass with Deep Hypothermic Circulatory Arrest. Scientific Reports 2019.
2) Biomarkers and associated outcomes after infant cardiothoracic surgery: I began research in this area by examining the utility of procalcitonin to distinguish the post-operative systemic inflammatory response from post-operative infection in 70 infants undergoing cardiothoracic surgery. I have also explored CD73 levels in our infants as an adjunct to my work with alkaline phosphatase and adenosine metabolism. In my most expansive biomarker work to date, I leveraged my K23 cohort to begin exploring the global metabolic shift that occurs following infant cardiac surgery. These findings were recently published in Journal of the American Heart Association.
a. Davidson J, Tong S, Hauck A, Lawson DS, Jaggers J, Kaufman J, Da Cruz E. Alkaline phosphatase activity after cardiothoracic surgery in infants and correlation with post-operative support and inflammation: a prospective cohort study. Critical Care. 2012 Aug 20: 16(4): R160.
b. Davidson J, Tong S, Hauck A, Lawson DS, Da Cruz E, Kaufman J. The kinetics of procalcitonin and C-reactive protein and the relationship to post-operative infection in young infants undergoing cardiovascular surgery. Ped Res. 2013 Sep; doi:10.1038/pr.2013.124
c. Jessica N. Persson, Christine H. Baird, Suhong Tong, Tracy T Urban, Jelena Klawitter, Paul E. Wischmeyer, and Jesse A. Davidson. Infant cardiopulmonary bypass: CD73 kinetics, association with clinical outcomes, and influence on serum adenosine production capacity. Ped. Res. 2017; doi:10.1038/pr.2017.325
d. Jesse A. Davidson, MD, MPH; Zachary Pfeifer, BS; Benjamin Frank, MD; Suhong Tong, MS; Tracy T. Urban, BS; Paul A. Wischmeyer, MD; Peter Mourani, MD; Bruce Landeck, MD; Uwe Christians, MD, PhD; Jelena Klawitter, PhD. Metabolomic fingerprinting of infants undergoing cardiopulmonary bypass: changes in metabolic pathways and association with mortality and cardiac intensive care unit length of stay. J Am Heart Assoc. 2018;7:e010711.
3) Biomarkers of ventricular remodeling and pulmonary vascular development in congenital heart disease: In this new research area, my colleague Dr. Benjamin Frank and I are working to understand the critical molecular pathways involved in pathologic ventricular and pulmonary vascular development in patients with congenital heart disease. We began work by evaluating left ventricular hypertrophy and remodeling ~1 year after surgical repair of left sided obstructive lesions. The data from that project have been published, identifying endothelin-1 as a novel potential biomarker in this disease. More recently, we began a larger project exploring endothelin-1 in the single ventricle heart disease population as well as the metabolomic and proteomic patterns associated with poor pulmonary blood vessel growth prior to stage 2 palliation and post-operative hypoxemia. This project was awarded an AHA Innovative Award and the enrolled cohort will be followed longitudinally through the Fontan operation.
a. Benjamin Steven Frank, Tracy T Urban, Suhong Tong, Courtney Cassidy, Max B Mitchell, Christopher S Nichols and Jesse A. Davidson. Endothelin-1 activation in pediatric patients undergoing surgical coarctation of the aorta repair. World Journal of Cardiology. 2017 Dec; 9(12):822-829.
b. Frank BS, Urban TT, Lewis K, Tong S, Cassidy C, Mitchell MB, Nichols CS, Davidson JA. Circulating biomarkers of left ventricular hypertrophy in pediatric coarctation of the aorta. Congenit Heart Dis. 2019 Jan 16.
4) Post-operative care in infants undergoing cardiac surgery: My initial interest in the study of post-operative care focused on vasoactive/inotropic support in the post-operative period. From a sub-analysis of my procalcitonin cohort I was able to validate the vasoactive-inotropic score initially reported by Gaies, et al., which we have now also validated in pediatric sepsis. Over the past two years I helped spearhead a multicenter collaborative, funded by the Gerber Foundation, that leverages automated data extraction to explore multiple aspects of repeated measure intensive care variables in our post-operative patients. The five centers involved have collected data on fluid, ventilator, and sedation practices in over 500 infants undergoing the Norwood procedure.
a. Davidson J, Tong S, Hancock H, Hauck A, Da Cruz E, Kaufman J. Prospective validation of the vasoactive-inotropic score and correlation to short-term outcomes in neonates and infants after cardiothoracic surgery. Intensive Care Med. 2012 Jul; 38(7): 1184-90.
b. Amanda M. McIntosh, Suhong Tong, Sara J. Deakyne, [*Jesse A. Davidson, *Halden F. Scott] *Co-senior authors. Validation of the Vasoactive Inotropic Score in Pediatric Sepsis. Ped Crit Care Med. 2017 Oct;18(10):1003-1005.