Review
Biochemistry & Molecular Biology
Erika L. Poitras, Stephen L. Gust, Paul M. Kerr, Frances Plane
Summary: Nitric oxide activates enzyme soluble guanylate cyclase to produce cGMP, which plays a key role in regulating intracellular calcium levels. PDE5 inhibitors like sildenafil prolong cGMP availability, making them first-line treatments for erectile dysfunction and approved for pulmonary arterial hypertension. Inhaled NO is currently used for neonatal persistent pulmonary hypertension, but alternative approaches are needed for unresponsive cases.
CURRENT MEDICINAL CHEMISTRY
(2021)
Review
Pharmacology & Pharmacy
Abraham Tettey, Yujie Jiang, Xiaohui Li, Ying Li
Summary: Pulmonary arterial hypertension (PAH) is a severe disease with high mortality even under treatment. Research has shown that the nitric oxide pathway plays a key role in PAH pathophysiology, with many drugs targeting this pathway. Novel compounds targeting on NO pathway hold great potential for future therapy, and understanding interactions with other pathways could lead to new drug discoveries for better clinical outcomes.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Pharmacology & Pharmacy
Qing-Fan Lin, Jing-Hong Rao, Shi-Mu Luo, Qing-Mu Wang, Li-Feng Deng, Xuan Chen, Chang-Di Chen, You-Fang Chen
Summary: This study found that gene polymorphisms of eNOS were associated with the development of PAH in newborns with CHD in South Fujian. Specifically, the GT/TT genotype of eNOS rs1799983 was associated with a higher risk of PAH, and this may be due to decreased nitric oxide production.
CLINICAL AND EXPERIMENTAL HYPERTENSION
(2022)
Review
Pediatrics
Feriel Fortas, Matteo Di Nardo, Nadya Yousef, Marc Humbert, Daniele De Luca
Summary: Persistent pulmonary hypertension of the neonate (PPHN) refractory to inhaled nitric oxide remains a common clinical challenge in neonatal critical care with negative outcomes. Pulmonary vasodilators have become available for use in neonates thanks to improved understanding of pulmonary hypertension pathobiology, but a comprehensive algorithm to guide treatment of refractory PPHN is still lacking.
EUROPEAN JOURNAL OF PEDIATRICS
(2021)
Review
Pharmacology & Pharmacy
Qi Jin, Dandan Chen, Xiaochun Zhang, Feng Zhang, Dongxiang Zhong, Dawei Lin, Lihua Guan, Wenzhi Pan, Daxin Zhou, Junbo Ge
Summary: Pulmonary arterial hypertension (PAH) is a malignant pulmonary vascular syndrome characterized by progressive pulmonary vascular resistance and pressure increase, leading to right heart failure and death. Although the exact mechanisms of PAH are not fully understood, vasoconstriction, remodeling, immune responses, and thrombosis are implicated. Over the past 30 years, PAH-specific therapies targeting three classical signaling pathways have significantly improved hemodynamics, function, and prognosis but have limited effects on pulmonary arterial pressure and right ventricular afterload. Current targeted agents can delay progression but cannot reverse vascular remodeling. New therapeutic drugs like sotatercept have emerged, injecting new vitality. This review summarizes general treatments and elaborates on specific drugs and combination strategies, highlighting the progress in finding new therapeutic targets for PAH.
Article
Physiology
Martha Hinton, James A. Thliveris, Grant M. Hatch, Shyamala Dakshinamurti
Summary: This study investigated the effects of sodium nitroprusside (NO donor) in treating hypoxic persistent pulmonary hypertension in newborns. The results showed that sodium nitroprusside can reduce reactive oxygen species accumulation, enhance cell relaxation, and inhibit adenylyl cyclase activity. Additionally, sodium nitroprusside can decrease protein nitrosylation levels. These findings provide insights into the reduced effectiveness of NO treatment in hypoxic pulmonary hypertension.
FRONTIERS IN PHYSIOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Yoogyeong Oh, Kyungtae Park, Sungwon Jung, Moonhyun Choi, Taihyun Kim, Yoojin Lee, Jae Young Choi, Yang-Hee Kim, Se Yong Jung, Jinkee Hong
Summary: In this study, open porous nitric oxide (NO) inhalers (OPNIs) with highly porous structures are synthesized to deliver nanomolar NO deep into the lungs through a nebulizer. The OPNIs exhibit vasodilatory and anti-inflammatory effects via sustained NO release, suggesting their potential as tools for pulmonary arterial hypertension (PAH) treatment.
Article
Pharmacology & Pharmacy
Amy M. Chinn, Cristina Salmeron, Jihyung Lee, Krishna Sriram, Eyal Raz, Paul A. Insel
Summary: This study investigates the regulation of cellular cAMP concentrations in dendritic cells (DCs) and identifies phosphodiesterase 4B (PDE4B) as a homeostatic regulator of cAMP levels. The findings suggest that targeting PDE4B could potentially be used to treat conditions with low cellular cAMP concentrations, including Th2-allergic asthma.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Cell Biology
A. T. Duarte-Silva, L. G. R. Ximenes, M. Guimaraes-Souza, I. Domith, R. Paes-de-Carvalho
Summary: The communication and interaction between developing neurons and neurotransmitters play crucial roles in the regulation of signaling pathways during central nervous system development.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Pharmacology & Pharmacy
Enio Setsuo Arakaki Pacini, Edwin Kerry Jackson, Rosely Oliveira Godinho
Summary: In the respiratory tract, extracellular 3',5'-cAMP is metabolized by enzymes to produce 5'-AMP, adenosine, and inosine, affecting airway smooth muscle contraction and relaxation. This extracellular enzymatic system plays a role in respiratory physiology and pathophysiology by generating interstitial adenosine from 3',5'-cAMP.
BIOCHEMICAL PHARMACOLOGY
(2021)
Article
Medicine, General & Internal
Yiwei Liu, Yifan Zhu, Chenyu Jiang, Zhanhao Su, Yi Yan, Bei Feng, Wen Mao, Yuyan Zhang, Xiaojian Wang, Zhuoming Xu, Hao Zhang
Summary: This study developed a novel portable device to produce nitric oxide (NO) for in-home inhalation therapy in patients with pulmonary artery hypertension (PAH). The device effectively reduced pulmonary arterial pressure and pulmonary vascular resistance in a pig model of PAH without causing major physiologic disruptions. This research paves the way for future clinical trials in PAH patients and other cardiopulmonary conditions.
Article
Obstetrics & Gynecology
Sourabh Verma, Rishi Lumba, Sadaf H. Kazmi, Michelle J. Vaz, Shrawani Soorneela Prakash, Sean M. Bailey, Pradeep Mally, Tara M. Randis
Summary: Inhaled iloprost shows beneficial effects in improving oxygenation indices in neonates with persistent pulmonary hypertension of the newborn who do not respond to inhaled nitric oxide therapy. Well-tolerated with no significant adverse effects observed, further well-designed prospective trials are needed to confirm the benefits of using inhaled iloprost as an adjunct treatment in these patients.
AMERICAN JOURNAL OF PERINATOLOGY
(2022)
Article
Pediatrics
Michael W. Cookson, Steven H. Abman, John P. Kinsella, Erica W. Mandell
Summary: The management of acute hypoxemic respiratory failure in newborns, especially when accompanied by persistent pulmonary hypertension, is a clinical challenge. Inhaled nitric oxide therapy has improved outcomes for neonates with persistent pulmonary hypertension, but some patients have an inadequate response and may require additional treatment.
SEMINARS IN FETAL & NEONATAL MEDICINE
(2022)
Review
Biochemistry & Molecular Biology
Aileen Jehle, Olga Garaschuk
Summary: Cyclic guanosine monophosphate (cGMP) plays a key role in many important signaling cascades in the body and brain, including phototransduction, olfaction, vasodilation, and functional hyperemia. Recent studies suggest that cGMP may act as a modulator in Alzheimer's disease (AD).
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Critical Care Medicine
Steven D. Nathan, Chunqin Deng, Christopher S. King, Hilary M. DuBrock, Jean Elwing, Sudarshan Rajagopal, Franz Rischard, Sandeep Sahay, Meredith Broderick, Eric Shen, Peter Smith, Victor F. Tapson, Aaron B. Waxman
Summary: Higher dosages of inhaled treprostinil have been shown to have greater benefits in preventing clinical worsening and achieving clinical improvement in patients with pulmonary hypertension resulting from interstitial lung disease.
Article
Obstetrics & Gynecology
Satyan Lakshminrusimha, Payam Vali, Praveen Chandrasekharan, Wade Rich, Anup Katheria
Summary: DCC + 100% O(2) for 60 seconds increases Qp in preterm lambs, possibly due to transient alveolar hyperoxia with systemic normoxia. DCC + CPAP with 100% O(2) for 60 seconds, followed by weaning to 30% O(2), achieves good SpO(2) levels in human infants, with high survival rate and no severe intraventricular hemorrhage.
AMERICAN JOURNAL OF PERINATOLOGY
(2023)
Letter
Obstetrics & Gynecology
Satyan Lakshminrusimha, Alexandra Leegwater, Pranjali Vadlaputi, Pranav Garlapati, Sanjay Chawla, Vaneet Kalra
JOURNAL OF PERINATOLOGY
(2023)
Editorial Material
Obstetrics & Gynecology
Lidia Park, Lee Donohue, Satyan Lakshminrusimha, Deepika Sankaran
JOURNAL OF PERINATOLOGY
(2023)
Article
Pediatrics
Sara C. Handley, Neha Kumbhat, Barry Eggleston, Elizabeth E. Foglia, Alexis S. Davis, Krisa Van Meurs, Satyan Lakshminrusimha, Michele Walsh, Kristi L. Watterberg, Myra H. Wyckoff, Abhik Das, Sara B. DeMauro
Summary: Delayed cord clamping is associated with lower rates of death or severe neurodevelopmental impairment among extremely preterm infants, and this relationship is not mediated by severe intraventricular hemorrhage. No significant differences were observed between umbilical cord milking and other methods of cord management.
ARCHIVES OF DISEASE IN CHILDHOOD-FETAL AND NEONATAL EDITION
(2023)
Editorial Material
Critical Care Medicine
Patrick J. McNamara, Satyan Lakshminrusimha
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
(2023)
Article
Pediatrics
Satyan Lakshminrusimha, Ola D. Saugstad, Maximo Vento
JOURNAL OF PEDIATRICS
(2023)
Article
Pediatrics
Nithya Sivakumar, Shoshana Newman-Lindsay, Deepika Sankaran, Satyan Lakshminrusimha, Lee Donohue
Summary: Through experiments on neonatal manikins, pre-clinical medical students demonstrated shorter ventilation time and higher confidence when using a neonatal facemask compared to the laryngeal mask airway (LMA). Further studies are needed to evaluate the use of supraglottic airways in providers with limited neonatal airway management experience and to promote proficiency and confidence in the use of the LMA.
Article
Pediatrics
Deepika Sankaran, Evan M. Giusto, Amy L. Lesneski, Morgan E. Hardie, Houssam M. Joudi, Emily C. A. Lane, Victoria L. Hammitt, Kirstie C. Tully, Payam Vali, Satyan Lakshminrusimha
Summary: The combination of perinatal acidemia and postnatal hyperoxia increases the incidence of HIE in newborn infants. Current guidelines recommend using 100% oxygen during chest compressions (CC) in neonatal cardiac arrest, but gradual weaning from 100% oxygen after ROSC can lead to hyperoxia and cerebral tissue injury. This study suggests that abrupt weaning to 21% oxygen after ROSC or using 21% oxygen during CC followed by upward titration may limit hyperoxia. Further clinical studies are needed to investigate optimal oxygen titration during neonatal resuscitation.
Article
Pediatrics
Munmun Rawat, Sylvia Gugino, Carmon Koenigsknecht, Justin Helman, Lori Nielsen, Deepika Sankaran, Jayasree Nair, Praveen Chandrasekharan, Satyan Lakshminrusimha
Summary: This study compared the effects of epinephrine and vasopressin on perinatal cardiac arrest and found that vasopressin had a lower incidence and longer time to return of spontaneous circulation (ROSC) compared to epinephrine, supporting the current recommendations for exclusive use of epinephrine in neonatal resuscitation.
Editorial Material
Pediatrics
Vasantha H. S. Kumar
Review
Pediatrics
Deepika Sankaran, Elizabeth Partridge, Satyan Lakshminrusimha
Summary: Congenital syphilis is a global concern with increasing incidence worldwide. It can result in a range of clinical manifestations and long-term disabilities in affected newborns. Prevention strategies include antenatal screening, timely treatment with penicillin, partner tracing and treatment, and health education programs. Early detection and treatment during pregnancy, particularly in high-risk mothers, are essential to prevent future cases of congenital syphilis.
Article
Pediatrics
Jana Krystofova Mike, Yasmine White, Rachel S. Hutchings, Christian Vento, Janica Ha, Ariana Iranmahboub, Hadiya Manzoor, Anya Gunewardena, Cheryl Cheah, Aijun Wang, Brian D. Goudy, Satyan Lakshminrusimha, Janel Long-Boyle, Jeffrey R. Fineman, Donna M. Ferriero, Emin Maltepe
Summary: Clemastine shows promise in treating demyelinating diseases but has no effect on neurodevelopmental outcomes following global ischemic insult.
Review
Pediatrics
Viraraghavan Vadakkencherry Ramaswamy, Tapas Bandyopadhyay, Sushma Nangia, Gunjana Kumar, Abdul Kareem Pullattayil, Daniele Trevisanuto, Charles Christoph Roehr, Satyan Lakshminrusimha
Summary: This systematic review and meta-analysis aimed to evaluate the effect of implementing immediate resuscitation without routine tracheal suctioning versus with routine suctioning in neonates born through meconium-stained amniotic fluid (MSAF). The results showed that the clinical benefit or harm of routine tracheal suctioning versus no suctioning could not be determined for the primary outcome of mortality or requirement of extracorporeal membrane oxygenation (ECMO). However, routine suctioning may have a lower risk of meconium aspiration syndrome (MAS) and respiratory morbidities in neonates diagnosed with MAS. Due to the very low certainty of evidence, further studies are needed.
Article
Obstetrics & Gynecology
Rhae Ana Gamber, Heather Blonsky, Madeleine McDowell, Satyan Lakshminrusimha
Summary: Despite a 7% decrease in US births, there has been a 2% increase in NICU admissions. The study found that NICU admission rates were lowest among infants born to mothers aged 20-29 years and increased with maternal age of 30 years or older.
JOURNAL OF PERINATOLOGY
(2023)
Article
Pediatrics
Munmun Rawat, Srinivasan Mani, Sylvia F. Gugino, Carmon Koenigsknecht, Justin Helman, Lori Nielsen, Jayasree Nair, Upender Munshi, Praveen Chandrasekharan, Satyan Lakshminrusimha
Summary: Bilateral femoral occlusion during chest compressions can increase the incidence of ROSC in neonatal resuscitation by increasing diastolic pressures, coronary and carotid blood flow. This low-tech intervention has the potential to improve survival and neurodevelopmental outcomes.
