Naiara Cristina Bessas , Evelyn Christine de Souza Arantes , Natasha Marques Cassani , Uriel Enrique Aquino Ruiz , Igor Andrade Santos , Daniel Oliveira Silva Martins , Ana Laura Costa Oliveira , Giovanna André Antoniucci , Arthur Henrique Cavalcante de Oliveira , Gilson DeFreitas-Silva , Ana Carolina Gomes Jardim , Renata Galvão de Lima
{"title":"Influence of diimine bidentate ligand in the nitrosyl and nitro terpyridine ruthenium complex on the HSA/DNA interaction and antiviral activity","authors":"Naiara Cristina Bessas , Evelyn Christine de Souza Arantes , Natasha Marques Cassani , Uriel Enrique Aquino Ruiz , Igor Andrade Santos , Daniel Oliveira Silva Martins , Ana Laura Costa Oliveira , Giovanna André Antoniucci , Arthur Henrique Cavalcante de Oliveira , Gilson DeFreitas-Silva , Ana Carolina Gomes Jardim , Renata Galvão de Lima","doi":"10.1016/j.niox.2024.04.006","DOIUrl":"https://doi.org/10.1016/j.niox.2024.04.006","url":null,"abstract":"<div><p>Nitric oxide (NO) acts in different physiological processes, such as blood pressure control, antiparasitic activities, neurotransmission, and antitumor action. Among the exogenous NO donors, ruthenium nitrosyl/nitro complexes are potential candidates for prodrugs, due to their physicochemical properties, such as thermal and physiological pH stability. In this work, we proposed the synthesis and physical characterization of the new nitro terpyridine ruthenium (II) complexes of the type [Ru<sup>II</sup>(L)(NO<sub>2</sub>)(tpy)]PF<sub>6</sub> where tpy = 2,2':6′,2″-terpyridine; L = 3,4-diaminobenzoic acid (bdq) or <em>o</em>-phenylenediamine (bd) and evaluation of influence of diimine bidentate ligand NH.NHq-R (R = H or COOH) in the HSA/DNA interaction as well as antiviral activity. The interactions between HSA and new nitro complexes [Ru<sup>II</sup>(L)(NO<sub>2</sub>)(tpy)]<sup>+</sup> were evaluated. The <em>K</em><sub>a</sub> values for the HSA–[Ru<sup>II</sup>(bdq)(NO<sub>2</sub>)(tpy)]<sup>+</sup> is 10 times bigger than HSA–[Ru<sup>II</sup>(bd)(NO<sub>2</sub>)(tpy)]<sup>+</sup>. The sites of interaction between HSA and the complexes via synchronous fluorescence suppression indicate that the [Ru<sup>II</sup>(bdq)(NO<sub>2</sub>)(tpy)]<sup>+</sup> is found close to the Trp-241 residue, while the [Ru<sup>II</sup>(bd)(NO<sub>2</sub>)(tpy)]<sup>+</sup> complex is close to Tyr residues. The interaction with fish sperm <em>fs</em>-DNA using direct spectrophotometric titration (K<sub>b</sub>) and ethidium bromide replacement (K<sub>SV</sub> and K<sub>app</sub>) showed weak interaction in the system <em>fs</em>-DNA-[Ru<sup>II</sup>(bdq)(NO)(tpy)]<sup>+</sup>. Furthermore, <em>fs</em>-DNA–[Ru<sup>II</sup>(bd)(NO<sub>2</sub>)(tpy)]<sup>+</sup> and <em>fs</em>-DNA–[Ru<sup>II</sup>(bd)(NO)(tpy)]<sup>3+</sup> system showed higher intercalation constant. Circular dichroism spectra for <em>fs</em>-DNA–[Ru<sup>II</sup>(bd)(NO<sub>2</sub>)(tpy)]<sup>+</sup> and <em>fs</em>-DNA–[Ru<sup>II</sup>(bd)(NO)(tpy)]<sup>3+</sup>, suggest semi-intercalative accompanied by major groove binding interaction modes. The [Ru<sup>II</sup>(bd)(NO<sub>2</sub>)(tpy)]<sup>+</sup> and [Ru<sup>II</sup>(bd)(NO)(tpy)]<sup>3+</sup> inhibit replication of Zika and Chikungunya viruses based in the nitric oxide release under <em>S</em>-nitrosylation reaction with cysteine viral.</p></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140549907","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Nitric oxide regulation of fetal and newborn lung development and function","authors":"Jesse D. Roberts Jr.","doi":"10.1016/j.niox.2024.04.005","DOIUrl":"https://doi.org/10.1016/j.niox.2024.04.005","url":null,"abstract":"<div><p>In the developing lung, nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) signaling are essential in regulating lung formation and vascular tone. Animal studies have linked many anatomical and pathophysiological features of newborn lung disease to abnormalities in the NO/cGMP signaling system. They have demonstrated that driving this system with agonists and antagonists alleviates many of them. This research has spurred the rapid clinical development, testing, and application of several NO/cGMP-targeting therapies with the hope of treating and potentially preventing significant pediatric lung diseases. However, there are instances when the therapeutic effectiveness of these agents is limited. Studies indicate that injury-induced disruption of several critical components within the signaling system may hinder the promise of some of these therapies. Recent research has identified basic mechanisms that suppress NO/cGMP signaling in the injured newborn lung. They have also pinpointed biomarkers that offer insight into the activation of these pathogenic mechanisms and their influence on the NO/cGMP signaling system's integrity in vivo. Together, these will guide the development of new therapies to protect NO/cGMP signaling and safeguard newborn lung development and function. This review summarizes the important role of the NO/cGMP signaling system in regulating pulmonary development and function and our evolving understanding of how it is disrupted by newborn lung injury.</p></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140545949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Timothy G. Gaulton , Yi Xin , Marcus Victor , Alice Nova , Maurizio Cereda
{"title":"Imaging the pulmonary vasculature in acute respiratory distress syndrome","authors":"Timothy G. Gaulton , Yi Xin , Marcus Victor , Alice Nova , Maurizio Cereda","doi":"10.1016/j.niox.2024.04.004","DOIUrl":"https://doi.org/10.1016/j.niox.2024.04.004","url":null,"abstract":"<div><p>Acute respiratory distress syndrome (ARDS) is characterized by a redistribution of regional lung perfusion that impairs gas exchange. While speculative, experimental evidence suggests that perfusion redistribution may contribute to regional inflammation and modify disease progression. Unfortunately, tools to visualize and quantify lung perfusion in patients with ARDS are lacking. This review explores recent advances in perfusion imaging techniques that aim to understand the pulmonary circulation in ARDS. Dynamic contrast-enhanced computed tomography captures first-pass kinetics of intravenously injected dye during continuous scan acquisitions. Different contrast characteristics and kinetic modeling have improved its topographic measurement of pulmonary perfusion with high spatial and temporal resolution. Dual-energy computed tomography can map the pulmonary blood volume of the whole lung with limited radiation exposure, enabling its application in clinical research. Electrical impedance tomography can obtain serial topographic assessments of perfusion at the bedside in response to treatments such as inhaled nitric oxide and prone position. Ongoing technological improvements and emerging techniques will enhance lung perfusion imaging and aid its incorporation into the care of patients with ARDS.</p></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140542854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Adapting nitric oxide: A review of its foundation, uses in austere medical conditions, and emerging applications","authors":"Brian Strickland , N. Stuart Harris","doi":"10.1016/j.niox.2024.04.003","DOIUrl":"https://doi.org/10.1016/j.niox.2024.04.003","url":null,"abstract":"<div><p>Nitric oxide was first identified as a novel and effective treatment for persistent pulmonary hypertension of the newborn (PPHN), and has since been found to be efficacious in treating acute respiratory distress syndrome (ARDS) and pulmonary hypertension. Physicians and researchers have also found it shows promise in resource-constrained settings, both within and outside of the hospital, such as in high altitude pulmonary edema (HAPE) and COVID-19. The treatment has been well tolerated in these settings, and is both efficacious and versatile when studied across a variety of clinical environments. Advancements in inhaled nitric oxide continue, and the gas is worthy of investigation as physicians contend with new respiratory and cardiovascular illnesses, as well as unforeseen logistical challenges.</p></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140540179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shamima Akhtar , Komal Sagar , Aishwarya Singh , Milind P. Hote , Ambuj Roy , Alpana Sharma
{"title":"Inflammation-induced sialin mediates nitrate efflux in dysfunctional endothelium affecting NO bioavailability","authors":"Shamima Akhtar , Komal Sagar , Aishwarya Singh , Milind P. Hote , Ambuj Roy , Alpana Sharma","doi":"10.1016/j.niox.2024.04.002","DOIUrl":"https://doi.org/10.1016/j.niox.2024.04.002","url":null,"abstract":"<div><h3>Aim</h3><p>The mechanism of NO bioavailability in endothelial dysfunction, the trigger for atherogenesis is still unclear as exogenous nitrate therapy fails to alleviate endothelial dysfunction. Recently, sialin, a nitrate transporter, has been linked to affect tissue nitrate/nitrite levels. Hence, we investigated the role of sialin in NO bioavailability in endothelial dysfunction.</p></div><div><h3>Methods</h3><p>Serum-starved HUVECs were stimulated with either TNFα or AT-2 for 24 h either alone or in the presence of autophagy inducer or autophagy inhibitor alone. Nitric oxide, nitrite, and nitrate levels were measured in cell supernatant and cell lysate. Quantitative real-time PCR, Annexin V-PI, and monocyte adhesion assays were performed. Immunofluorescence staining for sialin, vWF, and LC3 was performed. STRING database was used to create protein interacting partners for sialin.</p></div><div><h3>Results</h3><p>Sialin is strongly expressed in activated EC <em>in vitro</em> and atherosclerotic plaque as well as tumor neo-vessel ECs. Sialin mediates nitrate ion efflux and is negatively regulated by autophagy via mTOR pathway. Blocking sialin enhances NO bioavailability, autophagy, cell survival, and eNOS expression while decreasing monocyte adhesion. PPI shows LGALS8 to directly interact with sialin and regulate autophagy, cell-cell adhesion, and apoptosis.</p></div><div><h3>Conclusion</h3><p>Sialin is a potential novel therapeutic target for treating endothelial dysfunction in atherosclerosis and cancer.</p></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140351385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Herllan Vieira de Almeida, Laura Caetano Escobar da Silva, Marcelo Ganzarolli de Oliveira
{"title":"Nitric oxide-releasing photocrosslinked chitosan cryogels","authors":"Herllan Vieira de Almeida, Laura Caetano Escobar da Silva, Marcelo Ganzarolli de Oliveira","doi":"10.1016/j.niox.2024.03.006","DOIUrl":"https://doi.org/10.1016/j.niox.2024.03.006","url":null,"abstract":"<div><p>The highly porous morphology of chitosan cryogels, with submicrometric-sized pore cell walls, provides a large surface area which leads to fast water absorption and elevated swelling degrees. These characteristics are crucial for the applications of nitric oxide (NO) releasing biomaterials, in which the release of NO is triggered by the hydration of the material. In the present study, we report the development of chitosan cryogels (CS) with a porous structure of interconnected cells, with wall thicknesses in the range of 340–881 nm, capable of releasing NO triggered by the rapid hydration process. This property was obtained using an innovative strategy based on the functionalization of CS with two previously synthesized S-nitrosothiols: S-nitrosothioglycolic acid (TGA(SNO)) and S-nitrosomercaptosuccinic acid (MSA(SNO)). For this purpose, CS was previously methacrylated with glycidyl methacrylate and subsequently submitted to photocrosslinking and freeze-drying processes. The photocrosslinked hydrogels thus obtained were then functionalized with TGA(SNO) and MSA(SNO) in reactions mediated by carbodiimide. After functionalization, the hydrogels were frozen and freeze-dried to obtain porous S-nitrosated chitosan cryogels with high swelling capacities. Through chemiluminescence measurements, we demonstrated that CS-TGA(SNO) and CS-MSA(SNO) cryogels spontaneously release NO upon water absorption at rates of 3.34 × 10<sup>−2</sup> nmol mg<sup>−1</sup> min<sup>−1</sup> and 1.27 × 10<sup>−1</sup> nmol mg<sup>−1</sup> min<sup>−1</sup>, respectively, opening new perspectives for the use of CS as a platform for localized NO delivery in biomedical applications.</p></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140533816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Carbon monoxide poisoning and phototherapy","authors":"Luca Zazzeron , Walfre Franco , Rox Anderson","doi":"10.1016/j.niox.2024.04.001","DOIUrl":"https://doi.org/10.1016/j.niox.2024.04.001","url":null,"abstract":"<div><p>Carbon monoxide (CO) poisoning is a leading cause of poison-related morbidity and mortality worldwide. By binding to hemoglobin and other heme-containing proteins, CO reduces oxygen delivery and produces tissue damage. Prompt treatment of CO-poisoned patients is necessary to prevent acute and long-term complications. Oxygen therapy is the only available treatment. Visible light has been shown to selectively dissociate CO from hemoglobin with high efficiency without affecting oxygen affinity. Pulmonary phototherapy has been shown to accelerate the rate of CO elimination in CO poisoned mice and rats when applied directly to the lungs or via intra-esophageal or intra-pleural optical fibers. The extracorporeal removal of CO using a membrane oxygenator with optimal characteristic for blood exposure to light has been shown to accelerate the rate of CO illumination in rats with or without lung injury and in pigs. The development of non-invasive techniques to apply pulmonary phototherapy and the development of a compact, highly efficient membrane oxygenator for the extracorporeal removal of CO in humans may provide a significant advance in the treatment of CO poisoning.</p></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140351386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yun Yan , Nikolay Kamenshchikov , Ziyu Zheng , Chong Lei
{"title":"Inhaled nitric oxide and postoperative outcomes in cardiac surgery with cardiopulmonary bypass: A systematic review and meta-analysis","authors":"Yun Yan , Nikolay Kamenshchikov , Ziyu Zheng , Chong Lei","doi":"10.1016/j.niox.2024.03.004","DOIUrl":"10.1016/j.niox.2024.03.004","url":null,"abstract":"<div><p>Cardiac surgeries under cardiopulmonary bypass (CPB) are complex procedures with high incidence of complications, morbidity and mortality. The inhaled nitric oxide (iNO) has been frequently used as an important composite of perioperative management during cardiac surgery under CPB. We conducted a meta-analysis of published randomized clinical trials (RCTs) to assess the effects of iNO on reducing postoperative complications, including the duration of postoperative mechanical ventilation, length of intensive care unit (ICU) stay, length of hospital stay, mortality, hemodynamic improvement (the composite right ventricular failure, low cardiac output syndrome, pulmonary arterial pressure, and vasoactive inotropic score) and myocardial injury biomarker (postoperative troponin I levels). Subgroup analyses were performed to assess the effect of modification and interaction. These included iNO dosage, the timing and duration of iNO therapy, different populations (children and adults), and comparators (other vasodilators and placebo or standard care). A comprehensive search for iNO and cardiac surgery was performed on online databases. Twenty-seven studies were included after removing the duplicates and irrelevant articles. The results suggested that iNO could reduce the duration of mechanical ventilation, but had no significance in the ICU stay, hospital stay, and mortality. This may be attributed to the small sample size of the most included studies and heterogeneity in timing, dosage and duration of iNO administration. Well-designed, large-scale, multicenter clinical trials are needed to further explore the effect of iNO in improving postoperative prognosis in cardiovascular surgical patients.</p></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140331885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ya-Ying Chang , Yuh-Huey Chao , Wei-Horng Jean , Tzu-Yu Lin , Cheng-Wei Lu
{"title":"Nitric oxide and tumor necrosis factor-⍺ levels are negatively correlated in endotoxin tolerance recovery in vitro","authors":"Ya-Ying Chang , Yuh-Huey Chao , Wei-Horng Jean , Tzu-Yu Lin , Cheng-Wei Lu","doi":"10.1016/j.niox.2024.03.005","DOIUrl":"10.1016/j.niox.2024.03.005","url":null,"abstract":"<div><p>Endotoxin tolerance (ET) is the hyporesponsiveness to lipopolysaccharide (LPS) after prior exposure. It is characterized by the downregulation of pro-inflammatory cytokine levels. Although ET protects against inflammation, its abolishment or recovery is critical for immunity. Nitric oxide (NO) plays various roles in the development of ET; however, its specific role in ET recovery remains unknown. To induce ET, RAW264.7 cells (a murine macrophage cell line) were pre-exposed to LPS (LPS<sub>1</sub>, 100 ng/mL for 24 h) and subsequently re-stimulated with LPS (LPS<sub>2</sub>, 100 ng/mL for 24 h). Expression of cytokines, NO, nitrite and inducible NO synthase (iNOS) were measured after 0, 12, 24, and 36 h of resting after LPS<sub>1</sub> treatment with or without the iNOS-specific inhibitor, 1400W. LPS<sub>2</sub>-induced tumor necrosis factor-⍺ (TNF-⍺) and interleukin-6 (IL-6) were downregulated after LPS<sub>1</sub> treatment, confirming the development of ET. Notably, TNF-⍺ and IL-6 levels spontaneously rebounded after 12–24 h of resting following LPS<sub>1</sub> treatment. In contrast, levles of NO, nitrite and iNOS increased during ET development and decreased during ET recovery. Moreover, 1400W inhibited ET development and blocked the early production of NO (<12 h) during ET recovery. Our findings suggest a negative correlation between iNOS-induced NO and cytokine levels in the abolishment of ET.</p></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140318832","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Emanuele Rezoagli , Simone Redaelli , Edward A. Bittner , Roberto Fumagalli , Fumito Ichinose , Lorenzo Berra
{"title":"Role of hemolysis on pulmonary arterial compliance and right ventricular systolic function after cardiopulmonary bypass","authors":"Emanuele Rezoagli , Simone Redaelli , Edward A. Bittner , Roberto Fumagalli , Fumito Ichinose , Lorenzo Berra","doi":"10.1016/j.niox.2024.03.003","DOIUrl":"10.1016/j.niox.2024.03.003","url":null,"abstract":"<div><h3>Background</h3><p>Cardiopulmonary bypass (CPB) is associated with intravascular hemolysis which depletes endogenous nitric oxide (NO). The impact of hemolysis on pulmonary arterial compliance (PAC) and right ventricular systolic function has not been explored yet. We hypothesized that decreased NO availability is associated with worse PAC and right ventricular systolic function after CPB.</p></div><div><h3>Methods</h3><p>This is a secondary analysis of an observational cohort study in patients undergoing cardiac surgery with CPB at Massachusetts General Hospital, USA (2014–2015). We assessed PAC (stroke volume/pulmonary artery pulse pressure ratio), and right ventricular function index (RVFI) (systolic pulmonary arterial pressure/cardiac output), as well as NO consumption at 15 min, 4 h and 12 h after CPB. Patients were stratified by CPB duration. Further, we assessed the association between changes in NO consumption with PAC and RVFI between 15min and 4 h after CPB.</p></div><div><h3>Results</h3><p>PAC was lowest at 15min after CPB and improved over time (n = 50). RVFI was highest -worse right ventricular function- at CPB end and gradually decreased. Changes in hemolysis, PAC and RVFI differed over time by CPB duration. PAC inversely correlated with total pulmonary resistance (TPR). TPR and PAC positively and negatively correlated with RVFI, respectively. NO consumption between 15min and 4 h after CPB correlated with changes in PAC (−0.28 ml/mmHg, 95%CI −0.49 to −0.01, p = 0.012) and RVFI (0.14 mmHg*L<sup>−1</sup>*min, 95%CI 0.10 to 0.18, p < 0.001) after multivariable adjustments.</p></div><div><h3>Conclusion</h3><p>PAC and RVFI are worse at CPB end and improve over time. Depletion of endogenous NO may contribute to explain changes in PAC and RVFI after CPB.</p></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1089860324000405/pdfft?md5=73b385252e380faa74b2e9b63df47951&pid=1-s2.0-S1089860324000405-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140194292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}