J. William Gaynor
· Professor of Surgery at the Children's Hospital of PhiladelphiaVerifiedUniversity of Pennsylvania · Rehabilitation Medicine
Active 1916–2026
About
J. William Gaynor, MD, is a Professor of Surgery at the Children's Hospital of Philadelphia. He is actively involved in the Division of Cardiothoracic Surgery at The Children's Hospital of Philadelphia and holds the position of Director of the Fetal Neuroprotection and Neuroplasticity Program at the Center for Fetal Diagnosis & Treatment. His work focuses on pediatric cardiac surgery, neuroprotection, and neuroplasticity, contributing to advancements in fetal diagnosis and treatment of congenital heart conditions.
Research topics
- Medicine
- Internal medicine
- Pediatrics
- Environmental health
- Demography
- Cardiology
Selected publications
JTCVS Open · 2026-02-25
articleOpen accessObjectives: White matter injury (WMI) is a common neurologic complication in neonates with critical congenital heart disease (CHD) and is associated with adverse neurodevelopmental outcomes. Although intraoperative and perioperative risk factors have been extensively studied, emerging evidence suggests that preoperative factors, including time from birth to surgery, may play a critical role in neurologic injury. We hypothesize that birth day of the week is associated with time to surgery and thus neurologic injury. Methods: We performed a retrospective analysis of 192 neonates born at term with critical CHD, 167 of whom underwent pre- and postoperative magnetic resonance imaging of the brain as part of a prospective observational study. The birth day of week and time to surgery were analyzed in relation to neurologic injury and patient demographics. Results: = .02). Conclusions: The day of week of birth may be an underrecognized contributor for neurologic injury in neonates with CHD. Given that surgical scheduling practices may contribute to the association between day of birth and time-to-surgery, optimizing delivery timing and surgical access may reduce the burden of WMI in this vulnerable population.
Journal of the American Heart Association · 2026-01-19
articleOpen accessIndividuals with congenital heart disease are living well into adulthood, resulting in a growing population at risk for neurocognitive and psychosocial challenges. Numerous studies have described these risks in childhood, but significant gaps remain in our understanding of how those challenges evolve across stages of adulthood and how to optimally integrate neurocognitive and psychosocial care for adults with congenital heart disease. A multidisciplinary group of experts and patient partners assembled in April 2024 in Atlanta, GA, forming 3 working groups: (1) Genetics and Brain Health, (2) Characterizing Neuropsychological and Psychological Outcomes, and (3) Neuropsychological and Psychosocial Interventions. Current knowledge was reviewed, knowledge gaps were identified, and recommendations to address these gaps were formulated. Five critical questions regarding the characterization of neuropsychological and psychological outcomes of adults with congenital heart disease were prioritized for discussion: which neurocognitive and psychosocial domains should be prioritized in research and clinical care, what are the trajectories of neurocognitive and psychosocial functioning over the lifespan, how should neurocognitive and psychosocial screening be deployed, what should neurocognitive and psychosocial assessments include, and how do we make comprehensive neurocognitive and psychosocial care a reality. Although many gaps in knowledge were identified, particularly around characterizing neurocognitive trajectories throughout adulthood, there is substantial evidence of increased risk for poor psychosocial outcomes among adults with with congenital heart disease. Clinical and research advances must progress in tandem to address these risks. Specific recommendations for advancing this field over the next decade are offered.
The Journal of Pediatrics · 2026-04-17
articleOpen accessJournal of the American College of Cardiology · 2026-03-01 · 2 citations
articleOpen accessJournal of Thoracic and Cardiovascular Surgery · 2026-04-24
articleP49. Impact of Residual Lesions following Norwood Palliation
Journal of Thoracic and Cardiovascular Surgery · 2026-04-24
articleSenior authorThe Annals of Thoracic Surgery · 2026-04-01
articleOpen accessBACKGROUND: Selective antegrade cerebral perfusion (SACP) is increasingly used during neonatal aortic arch surgery, yet practices remain inconsistent across surgeons and institutions due to limited evidence and lack of consensus. This study aimed to characterize deep hypothermic circulatory arrest (DHCA) and SACP practices among congenital heart surgeons internationally, including temperature, flow rate, and monitoring. METHODS: A 124-question electronic survey was distributed to congenital heart surgeons worldwide through the World Society for Pediatric and Congenital Heart Surgery from November 2024 to February 2025. Responses were limited to currently practicing or recently retired surgeons. RESULTS: The survey was completed by 104 surgeons (95.2% active, 4.8% retired). Respondents were predominantly men (93.3%) with a median age of 53 years and 19 years in practice. SACP was used exclusively by 69.2% and DHCA by 9.6%, whereas 21.2% selected between techniques based on anatomy or anticipated arrest duration. A change in individual practice was reported by 41% of the respondents, most transitioning from DHCA to SACP-particularly among older surgeons (median age 60 vs 48 years, P < .001). Among those using SACP, 78.3% used it alone and 21.7% combined it with lower body perfusion. Target SACP temperature ranged widely from <20 °C to 35 °C, with lower targets for longer procedures. Flow determination also varied: 59.6% used weight-based calculations, whereas others adjusted by pressure or near-infrared spectroscopy. After initiation, flow was titrated to right radial artery pressure (38.0%) or near-infrared spectroscopy (55.4%). CONCLUSIONS: Substantial variability persists in neuroprotective strategies during neonatal aortic arch repair, emphasizing the need for evidence-based standardization and high-fidelity neuromonitoring strategies.
Neonatology · 2026-01-30 · 1 citations
articleINTRODUCTION: In congenital diaphragmatic hernia (CDH), infants with left heart disease are at the highest risk of extracorporeal membrane oxygenation (ECMO) and mortality, but the association between maternal-fetal environmental characteristics and these adverse postnatal outcomes is unknown. METHODS: Maternal-fetal dyads with CDH who were enrolled in a single-center birth defects biorepository and also in comprehensive postnatal echocardiographic studies from 2019 to 2023 were included in a retrospective analysis. Geocoded census tract was used to generate maternal neighborhood characteristics from conception to birth from the American Community Survey (ACS), Child Opportunity Index, Air Quality Index (AQI), and Food and Drug Administration percent food insecurity. Infant characteristics including ECMO and survival were abstracted from the biorepository. Quantification of left heart hypoplasia and/or left ventricular (LV) dysfunction was performed on postnatal echocardiograms. Disease-specific and neighborhood characteristics were compared by ECMO/mortality status and by the presence of left heart disease. RESULTS: Seventy-seven patients (58% male, 82% left CDH, 68% liver herniation) were included. Twenty-four (31%) patients required ECMO, 61 (77%) had left heart hypoplasia or LV dysfunction, and 19 (25%) received pulmonary vasodilators. ECMO utilization was higher in patients with left heart disease. Worse neighborhood air quality by AQI was identified in patients who required ECMO and/or died and in patients with left heart disease. A higher percentage of female-headed households was seen in patients who required ECMO and/or died. CONCLUSION: Maternal neighborhood characteristics may impact outcomes in CDH. Future study of these environmental factors may inform individualized treatment strategies.
Circulation · 2025-11-03
articleIntroduction: Excess lipolysis and dysregulated fatty acid oxidation can exacerbate neuroglial injury and impair neurodevelopment. Neurodevelopment is also regulated by histone deacetylation and methylation, which often repress gene transcription and can alter cerebral metabolism. It is unknown if fatty acid metabolism and histone modifications are altered in the neonatal brain following cardiopulmonary bypass (CPB). Research Question: This study sought to determine if histone modifications regulating chromatin accessibility and gene transcription are altered in the brain or associated with changes in cerebral metabolism at 12-24hrs post-CPB. Methods: Fifteen neonatal swine underwent 3hrs of CPB prior to decannulation and survival for 12hrs, 18hrs, or 24hrs (N=5 per cohort). Three additional piglets underwent similar sham procedures with 4hr survival. Cortical brain tissue was then analyzed with liquid chromatography-mass spectrometry using an untargeted approach to quantify 129 metabolites and 45 histone modifications in each sample. Histone modifications with a statistically significant fold-change (FC) post-CPB ( P <0.0001) were correlated with metabolites across all timepoints of analysis. Results: In total, 6/45 (13%) histone modifications were significantly altered in cortical brain tissue following CPB. The acetylation of histone H4 on lysine residue 16 (H4K16ac) was reduced at 12-24hrs post-CPB (FC=0.7-0.8, P <0.0001 ), while trimethylation was enriched on histone H4 at lysine residue 20 (H4K20me3: FC=1.5-2.4; Figure ). H4K20me3 enrichment directly correlated with intermediates of fatty acid metabolism, specifically polyunsaturated long-chain acylcarnitines ( Table ). Histone H3 variants had enriched mono-methylation on lysine 36 residues at 12hrs (H33K36me1: FC=6.9, P <0.0001 ) and 18hrs post-CPB (H31K36me1: FC=1.6, P <0.0001 ). Histone H3 mono-methylation was also enriched on lysine residue 23 (H3K23me1) at 18hrs post-CPB (FC=5.1, P <0.0001 ), and phosphorylation on serine residue 10 (H3S10ph) was enriched at 24hrs post-CPB (FC=6.2, P <0.0001 ). Conclusion: Dynamic changes in histone methylation and deacetylation post-CPB may impact metabolic homeostasis in the neonatal brain during critical periods of neurodevelopment. Further investigations are warranted to elucidate how alterations in lipolysis, fatty acid oxidation, chromatin accessibility, and gene transcription may affect myelination, neuroglial injury, and neurodevelopment in neonates requiring cardiac surgery.
Circulation · 2025-11-03
articleBackground: Nitric oxide signaling can mediate ischemia-reperfusion injury by altering vascular resistance and inflammatory responses, including the production and degradation of reactive oxygen species (ROS). Excess ROS contributes to oxidative stress and can impair mitochondrial energy synthesis via oxidative phosphorylation (OxPhos). We previously demonstrated that ROS and mitochondrial respiration in the neonatal brain can be adversely affected following deep hypothermic circulatory arrest (DHCA). It is unknown if inhaled nitric oxide (iNO) alters cerebral ROS and OxPhos capacity post-DHCA. Research Question: Does intraoperative iNO therapy affect cerebral ROS, OxPhos capacity, and neurologic injury or recovery after DHCA? Methods: Ten neonatal swine underwent DHCA (90min, 18 o C) prior to reperfusion and rewarming, of which half were randomized and blinded to receive iNO (40ppm) intraoperatively (DHCA 90min+iNO , N=5) and half did not (DHCA 90min , N=5). Five additional piglets underwent sham procedures without bypass, DHCA, or iNO. Upon study completion, brain tissue was analyzed using high-resolution mitochondrial respirometry. Immunohistochemistry assessed microglia- and neuron-specific inflammation using antibodies for ionized calcium-binding adaptor molecule 1 (IBA-1) and beta-amyloid precursor protein (β-APP), respectively. Results: Following DHCA 90min+iNO , cerebral ROS production did not decline compared to DHCA 90min animals ( P =0.210, Figure ), and OxPhos capacity via mitochondrial complex I was reduced compared to both sham ( P =0.041 ) and DHCA 90min animals ( P =0.078, Figure ). Rare and frequent β-APP staining was more common after DHCA 90min and DHCA 90min+iNO compared to sham animals ( P =0.055), and IBA-1 staining in subcortical white matter increased following DHCA 90min+iNO compared to both sham ( P =0.001 ) and DHCA 90min animals ( P =0.013 , Figure ). Conclusions iNO does not attenuate cerebral ROS following DHCA, and may even increase microglial inflammation and post-operative white matter injury by impairing energy synthesis via mitochondrial complex I. Further studies are warranted to elucidate how regional changes in the cerebral microcirculation may affect the delivery, efficacy, and toxicity of targeted therapeutics following DHCA. Improved insights into how microglial inflammation and mitochondrial energy synthesis mediate neurologic injury and recovery post-DHCA might ultimately help improve neurocognitive outcomes in congenital cardiac surgery.
Recent grants
NIH · $3.7M · 2009
NIH · $2.7M · 2016
Frequent coauthors
- 683 shared
Thomas L. Spray
University of Pennsylvania
- 446 shared
Jeffrey P. Jacobs
University of Florida
- 318 shared
Susan C. Nicolson
Children's Hospital of Philadelphia
- 317 shared
Gil Wernovsky
Children's National
- 290 shared
Marshall L. Jacobs
Johns Hopkins University
- 253 shared
Constantine Mavroudis
Children's Hospital of Philadelphia
- 221 shared
Chitra Ravishankar
University of Pennsylvania
- 214 shared
Sara K. Pasquali
University of Michigan–Ann Arbor
Education
- 1978
B.S., Mathematics
Davidson College
- 1982
M.D.
Medical University of South Carolina
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