Rachel Tan , Marissa N. Baranauskas , Sean T. Karl , Joaquin Ortiz de Zevallos , Ren-Jay Shei , Hunter L. Paris , Chad C. Wiggins , Stephen J. Bailey
{"title":"Effects of dietary nitrate supplementation on peak power output: Influence of supplementation strategy and population","authors":"Rachel Tan , Marissa N. Baranauskas , Sean T. Karl , Joaquin Ortiz de Zevallos , Ren-Jay Shei , Hunter L. Paris , Chad C. Wiggins , Stephen J. Bailey","doi":"10.1016/j.niox.2023.06.004","DOIUrl":"10.1016/j.niox.2023.06.004","url":null,"abstract":"<div><p>Increasing evidence indicates that dietary nitrate supplementation has the potential to increase muscular power output during skeletal muscle contractions. However, there is still a paucity of data characterizing the impact of different nitrate dosing regimens on nitric oxide bioavailability and its potential ergogenic effects across various population groups. This review discusses the potential influence of different dietary nitrate supplementation strategies on nitric oxide bioavailability and muscular peak power output in healthy adults, athletes, older adults and some clinical populations. Effect sizes were calculated for peak power output and absolute and/or relative nitrate doses were considered where applicable. There was no relationship between the effect sizes of peak power output change following nitrate supplementation and when nitrate dosage when considered in absolute or relative terms. Areas for further research are also recommended including a focus on nitrate dosing regimens that optimize nitric oxide bioavailability for enhancing peak power at times of increased muscular work in a variety of healthy and disease populations.</p></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10606713","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}
Yumi Okamoto, Junto Otsuka, Mao Aoki, Tatsuro Amano
{"title":"Transdermal iontophoretic application of l-NAME is available in sweating research induced by heat stress in young healthy adults","authors":"Yumi Okamoto, Junto Otsuka, Mao Aoki, Tatsuro Amano","doi":"10.1016/j.niox.2023.08.001","DOIUrl":"10.1016/j.niox.2023.08.001","url":null,"abstract":"<div><p>Iontophoretic transdermal administration of <em>N</em><sup>G</sup>-nitro-<sub><span>l</span></sub>-arginine methyl ester hydrochloride [<span>l</span>-NAME, a nitric oxide synthase (NOS) inhibitor] has been used as a non-invasive evaluation of NOS-dependent mechanisms in human skin. However, the availability has yet to be investigated in sweating research. Prior observations using invasive techniques (e.g., intradermal microdialysis technique) to administer <span>l</span>-NAME have implicated that NOS reduces sweating induced by heat stress but rarely influences the response induced by the administration of cholinergic muscarinic receptor agonists. Therefore, we investigated whether the transdermal iontophoretic administration of <span>l</span>-NAME modulates sweating similar to those prior observations. Twenty young healthy adults (10 males, 10 females) participated in two experimental protocols on separate days. Before each protocol, saline (control) and 1% <span>l</span>-NAME were bilaterally administered to the forearm skin via transdermal iontophoresis. In protocol 1, 0.001% and 1% pilocarpine were iontophoretically administered at <span>l</span>-NAME-treated and untreated sites. In protocol 2, passive heating was applied by immersing the lower limbs in hot water (43 °C) until the rectal temperature increased by 0.8 °C above baseline. The sweat rate was continuously measured throughout both protocols. Pilocarpine-induced sweat rate was not significantly different between the control and <span>l</span>-NAME-treated sites in both pilocarpine concentrations (<em>P</em> ≥ 0.316 for the treatment effect and interaction of treatment and pilocarpine concentration). The sweat rate during passive heating was attenuated at the <span>l</span>-NAME-treated site relative to the control (treatment effect, <em>P</em> = 0.020). Notably, these observations are consistent with prior sweating studies administrating <span>l</span>-NAME into human skin using intradermal microdialysis techniques. Based on the similarity of our results with already known observations, we conclude that transdermal iontophoresis of <span>l</span>-NAME is a valid non-invasive technique for the investigation of the mechanisms of sweating related to NOS during heat stress.</p></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10282013","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}
Li Feng, Lijuan Wei, Yayu Liu, Jiaxuan Ren, Weibiao Liao
{"title":"Carbon monoxide/heme oxygenase system in plant: Roles in abiotic stress response and crosstalk with other signals molecules","authors":"Li Feng, Lijuan Wei, Yayu Liu, Jiaxuan Ren, Weibiao Liao","doi":"10.1016/j.niox.2023.06.005","DOIUrl":"10.1016/j.niox.2023.06.005","url":null,"abstract":"<div><p>Carbon monoxide (CO) has been recognized as a crucial gasotransmitter mainly produced by heme oxygenase (HO)-catalyzed heme degradation in plant. Recent studies have shown that CO plays an important role in regulating growth and development of plant, as well as and responding to a variety of abiotic stresses. Meanwhile, many studies have reported on CO working in combination with other signal molecules to mitigate abiotic stress. Here, we presented a comprehensive overview of recent developments in which CO reduces plant damage caused by abiotic stresses. The regulation of antioxidant system, photosynthetic system, ion balance and transport are the main mechanisms of CO-alleviated abiotic stress. We also proposed and discussed the relationship between CO and other signal molecules, including nitric oxide (NO), hydrogen sulfide (H<sub>2</sub>S), hydrogen gas (H<sub>2</sub>), abscisic acid (ABA), indole 3-acetic acid (IAA), gibberellin (GA), cytokine (CTK), salicylic acid (SA), jasmonic acid (JA), hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) and calcium ion (Ca<sup>2+</sup>). Furthermore, the important role of <em>HO</em> genes in alleviating abiotic stress was also discussed. We proposed promising and new research directions for the study of plant CO, which can provide further insights on the role of CO in plant growth and development under abiotic stress.</p></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10282562","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}
William S. Zoughaib , Richard L. Hoffman , Brandon A. Yates , Ranjani N. Moorthi , Kenneth Lim , Andrew R. Coggan
{"title":"Short-term beetroot juice supplementation improves muscle speed and power but does not reduce blood pressure or oxidative stress in 65–79 y old men and women","authors":"William S. Zoughaib , Richard L. Hoffman , Brandon A. Yates , Ranjani N. Moorthi , Kenneth Lim , Andrew R. Coggan","doi":"10.1016/j.niox.2023.05.005","DOIUrl":"10.1016/j.niox.2023.05.005","url":null,"abstract":"<div><p>We have previously demonstrated that acute ingestion of inorganic nitrate (NO<sub>3</sub><sup>−</sup>)-rich beetroot juice (BRJ), a source of nitric oxide (NO) via the NO<sub>3</sub><sup>−</sup> → nitrite (NO<sub>2</sub><sup>−</sup>) → NO pathway, can improve muscle speed and power in older individuals. It is not known, however, whether this effect is maintained or perhaps even enhanced with repeated ingestion, or if tolerance develops as with organic nitrates, e.g., nitroglycerin. Using a double-blind, placebo-controlled, crossover design, we therefore studied 16 community-dwelling older (age 71 ± 5 y) individuals after both acute and short-term (i.e., daily for 2 wk) BRJ supplementation. Blood samples were drawn and blood pressure was measured periodically during each ∼3 h experiment, with muscle function determined using isokinetic dynamometry. Acute ingestion of BRJ containing 18.2 ± 6.2 mmol of NO<sub>3</sub><sup>−</sup> increased plasma NO<sub>3</sub><sup>−</sup> and NO<sub>2</sub><sup>−</sup> concentrations 23 ± 11 and 2.7 ± 2.1-fold over placebo, respectively. This was accompanied by 5 ± 11% and 7 ± 13% increases in maximal knee extensor speed (Vmax) and power (Pmax), respectively. After daily supplementation for 2 wk, BRJ ingestion elevated NO<sub>3</sub><sup>−</sup> and NO<sub>2</sub><sup>−</sup> levels 24 ± 12 and 3.3 ± 4.0-fold, respectively, whereas Vmax and Pmax were 7 ± 9% and 9 ± 11% higher than baseline. No changes were observed in blood pressure or in plasma markers of oxidative stress with either acute or short-term NO<sub>3</sub><sup>−</sup> supplementation. We conclude that both acute and short-term dietary NO<sub>3</sub><sup>−</sup> supplementation result in similar improvements in muscle function in older individuals. The magnitudes of these improvements are sufficient to offset the decline resulting from a decade or more of aging and are therefore likely to be clinically significant.</p></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10527284/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10271790","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}
Manivannan Yegambaram , Sanjiv Kumar , Xiaomin Wu , Qing Lu , Xutong Sun , Alejandro Garcia Flores , Mary Louise Meadows , Scott Barman , David Fulton , Ting Wang , Jeffrey R. Fineman , Stephen M. Black
{"title":"Endothelin-1 acutely increases nitric oxide production via the calcineurin mediated dephosphorylation of Caveolin-1","authors":"Manivannan Yegambaram , Sanjiv Kumar , Xiaomin Wu , Qing Lu , Xutong Sun , Alejandro Garcia Flores , Mary Louise Meadows , Scott Barman , David Fulton , Ting Wang , Jeffrey R. Fineman , Stephen M. Black","doi":"10.1016/j.niox.2023.08.004","DOIUrl":"10.1016/j.niox.2023.08.004","url":null,"abstract":"<div><p>Endothelin (ET)-1 is an endothelial-derived peptide that exerts biphasic effects on nitric oxide (NO) levels in endothelial cells such that acute exposure stimulates-while sustained exposure attenuates-NO production. Although the mechanism involved in the decrease in NO generation has been identified but the signaling involved in the acute increase in NO is still unresolved. This was the focus of this study. Our data indicate that exposing pulmonary arterial endothelial cells (PAEC) to ET-1 led to an increase in NO for up to 30min after which levels declined. These effects were attenuated by ET receptor antagonists. The increase in NO correlated with significant increases in pp60<sup>Src</sup> activity and increases in eNOS phosphorylation at Tyr83 and Ser1177. The ET-1 mediated increase in phosphorylation and NO generation were attenuated by the over-expression of a pp60<sup>Src</sup> dominant negative mutant. The increase in pp60<sup>Src</sup> activity correlated with a reduction in the interaction of Caveolin-1 with pp60<sup>Src</sup> and the calcineurin-mediated dephosphorylation of caveolin-1 at three previously unidentified sites: Thr91, Thr93, and Thr95. The calcineurin inhibitor, Tacrolimus, attenuated the acute increase in pp60<sup>Src</sup> activity induced by ET-1 and a calcineurin siRNA attenuated the ET-1 mediated increase in eNOS phosphorylation at Tyr83 and Ser1177 as well as the increase in NO. By using a Caveolin-1 celluSpot peptide array, we identified a peptide targeting a sequence located between aa 41–56 as the pp60<sup>Src</sup> binding region. This peptide fused to the TAT sequence was found to decrease caveolin-pp60<sup>Src</sup> interaction, increased pp60<sup>Src</sup> activity, increased eNOS pSer1177 and NO levels in PAEC and induce vasodilation in isolated aortic rings in wildtype but not eNOS knockout mice. Together, our data identify a novel mechanism by which ET-1 acutely increases NO via a calcineurin-mediated dephosphorylation of caveolin-1 and the subsequent stimulation of pp60<sup>Src</sup> activity, leading to increases in phosphorylation of eNOS at Tyr83 and Ser1177.</p></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2023-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10196737","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}
Kaitlin A. Freeberg , Katelyn R. Ludwig , Michel Chonchol , Douglas R. Seals , Matthew J. Rossman
{"title":"NAD+-boosting compounds enhance nitric oxide production and prevent oxidative stress in endothelial cells exposed to plasma from patients with COVID-19","authors":"Kaitlin A. Freeberg , Katelyn R. Ludwig , Michel Chonchol , Douglas R. Seals , Matthew J. Rossman","doi":"10.1016/j.niox.2023.08.003","DOIUrl":"https://doi.org/10.1016/j.niox.2023.08.003","url":null,"abstract":"<div><p>SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), induces vascular endothelial dysfunction, but the mechanisms are unknown. We tested the hypothesis that the “circulating milieu” (plasma) of patients with COVID-19 would cause endothelial cell dysfunction (characterized by lower nitric oxide (NO) production), which would be linked to greater reactive oxygen species (ROS) bioactivity and depletion of the critical metabolic co-substrate, nicotinamide adenine dinucleotide (NAD<sup>+</sup>). We also investigated if treatment with NAD<sup>+</sup>-boosting compounds would prevent COVID-19-induced reductions in endothelial cell NO bioavailability and oxidative stress. Human aortic endothelial cells (HAECs) were exposed to plasma from men and women (age 18–85 years) who were hospitalized and tested positive (n = 34; 20 M) or negative (n = 13; 10 M) for COVID-19. HAECs exposed to plasma from patients with COVID-19 also were co-incubated with NAD<sup>+</sup> precursors nicotinamide riboside (NR) or nicotinamide mononucleotide (NMN). Acetylcholine-stimulated NO production was 27% lower and ROS bioactivity was 54% higher in HAECs exposed to plasma from patients with COVID-19 (both p < 0.001 vs. control); these responses were independent of age and sex. NAD<sup>+</sup> concentrations were 30% lower in HAECs exposed to plasma from patients with COVID-19 (p = 0.001 vs. control). Co-incubation with NR abolished COVID-19-induced reductions in NO production and oxidative stress (both p > 0.05 vs. control). Co-treatment with NMN produced similar results. Our findings suggest the circulating milieu of patients with COVID-19 promotes endothelial cell dysfunction, characterized by lower NO bioavailability, greater ROS bioactivity, and NAD<sup>+</sup> depletion. Supplementation with NAD<sup>+</sup> precursors may exert a protective effect against COVID-19-evoked endothelial cell dysfunction and oxidative stress.</p></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2023-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49829311","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":"Hydrogen sulfide: From a toxic gas to a potential therapy for COVID-19 and inflammatory disorders","authors":"Mohit Kumar","doi":"10.1016/j.niox.2023.08.002","DOIUrl":"10.1016/j.niox.2023.08.002","url":null,"abstract":"<div><p>COVID-19 has been shown to induce inflammatory disorders and CNS manifestations. Swift and efficient treatment strategies are urgently warranted for the management of COVID, inflammatory and neurological disorders. Hydrogen sulfide (H<sub>2</sub>S) has been associated with several clinical disorders due to its potential to influence a broad range of biological signalling pathways. According to recent clinical studies, COVID patients with lower physiological H<sub>2</sub>S had higher fatality rates. These findings clearly demonstrate an inverse correlation between H<sub>2</sub>S levels and the severity of COVID-19. H<sub>2</sub>S has been proposed as a protective molecule because of its antioxidant, anti-inflammatory, and antiviral properties. Various H<sub>2</sub>S-releasing prodrugs, hybrids and natural compounds have been tested for their therapeutic efficacy in viral infections and inflammatory disorders. In this review, I am highlighting the rationale for using H<sub>2</sub>S-based interventions for the management of COVID-19 and post-infection inflammatory disorders including neuroinflammation. I am also proposing therepurposing of existing H<sub>2</sub>S-releasing prodrugs, developing new NO-H<sub>2</sub>S-hybrids, targeting H<sub>2</sub>S metabolic pathways, and using H<sub>2</sub>S-producing dietary supplements as viable defensive strategies against SARS-CoV-2 infection and COVID-19 pathologies.</p></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2023-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10199286","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 as a mediator of exercise performance: NO pain NO gain","authors":"Jason D. Allen","doi":"10.1016/j.niox.2023.04.006","DOIUrl":"10.1016/j.niox.2023.04.006","url":null,"abstract":"","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9657732","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}
Shuying Huang , Xiaonan Chen , Jianan Pan , Hui Zhang , Jiahan Ke , Lin Gao , Alex Chia Yu Chang , Junfeng Zhang , Huili Zhang
{"title":"Hydrogen sulfide alleviates heart failure with preserved ejection fraction in mice by targeting mitochondrial abnormalities via PGC-1α","authors":"Shuying Huang , Xiaonan Chen , Jianan Pan , Hui Zhang , Jiahan Ke , Lin Gao , Alex Chia Yu Chang , Junfeng Zhang , Huili Zhang","doi":"10.1016/j.niox.2023.05.002","DOIUrl":"10.1016/j.niox.2023.05.002","url":null,"abstract":"<div><h3>Aim</h3><p>Increasing evidence has proposed that mitochondrial abnormalities may be an important factor contributing to the development of heart failure with preserved ejection fraction (HFpEF). Hydrogen sulfide (H<sub>2</sub>S) has been suggested to play a pivotal role in regulating mitochondrial function. Therefore, the present study was designed to explore the protective effect of H<sub>2</sub>S on mitochondrial dysfunction in a multifactorial mouse model of HFpEF.</p></div><div><h3>Methods</h3><p>Wild type, 8-week-old, male C57BL/6J mice or cardiomyocyte specific-<em>Cse</em> (Cystathionine γ-lyase, a major H<sub>2</sub>S-producing enzyme) knockout mice (CSE<sup>cko</sup>) were given high-fat diet (HFD) and <span>l</span>-NAME (an inhibitor of constitutive nitric oxide synthases) or standardized chow. After 4 weeks, mice were randomly administered with NaHS (a conventional H<sub>2</sub>S donor), ZLN005 (a potent transcriptional activator of PGC-1α) or vehicle. After additional 4 weeks, echocardiogram and mitochondrial function were evaluated. Expression of PGC-1α, NRF1 and TFAM in cardiomyocytes was assayed by Western blot.</p></div><div><h3>Results</h3><p>Challenging with HFD and <span>l</span>-NAME in mice not only caused HFpEF but also inhibited the production of endogenous H<sub>2</sub>S in a time-dependent manner. Meanwhile the expression of PGC-1α and mitochondrial function in cardiomyocytes were impaired. Supplementation with NaHS not only upregulated the expression of PGC-1α, NRF1 and TFAM in cardiomyocytes but also restored mitochondrial function and ultrastructure, conferring an obvious improvement in cardiac diastolic function. In contrast, cardiac deletion of CSE gene aggravated the inhibition of PGC-1α-NRF1-TFAM pathway, mitochondrial abnormalities and diastolic dysfunction. The deleterious effect observed in CSE<sup>cko</sup> HFpEF mice was partially counteracted by pre-treatment with ZLN005 or supplementation with NaHS.</p></div><div><h3>Conclusion</h3><p>Our findings have demonstrated that H<sub>2</sub>S ameliorates left ventricular diastolic dysfunction by restoring mitochondrial abnormalities via upregulating PGC-1α and its downstream targets NRF1 and TFAM, suggesting the therapeutic potential of H<sub>2</sub>S supplementation in multifactorial HFpEF.</p></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9757452","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}
Stefano Spina , Francesco Marrazzo , Caio C.A. Morais , Marcus Victor , Clarissa Forlini , Marcello Guarnieri , Luca Bastia , Riccardo Giudici , Gabriele Bassi , Yi Xin , Maurizio Cereda , Marcelo Amato , Thomas Langer , Lorenzo Berra , Roberto Fumagalli
{"title":"Modulation of pulmonary blood flow in patients with acute respiratory failure","authors":"Stefano Spina , Francesco Marrazzo , Caio C.A. Morais , Marcus Victor , Clarissa Forlini , Marcello Guarnieri , Luca Bastia , Riccardo Giudici , Gabriele Bassi , Yi Xin , Maurizio Cereda , Marcelo Amato , Thomas Langer , Lorenzo Berra , Roberto Fumagalli","doi":"10.1016/j.niox.2023.05.001","DOIUrl":"10.1016/j.niox.2023.05.001","url":null,"abstract":"<div><h3>Background</h3><p>Impairment of ventilation and perfusion (V/Q) matching is a common mechanism leading to hypoxemia in patients with acute respiratory failure requiring intensive care unit (ICU) admission. While ventilation has been thoroughly investigated, little progress has been made to monitor pulmonary perfusion at the bedside and treat impaired blood distribution. The study aimed to assess real-time changes in regional pulmonary perfusion in response to a therapeutic intervention.</p></div><div><h3>Methods</h3><p>Single-center prospective study that enrolled adult patients with ARDS caused by SARS-Cov-2 who were sedated, paralyzed, and mechanically ventilated. The distribution of pulmonary perfusion was assessed through electrical impedance tomography (EIT) after the injection of a 10-ml bolus of hypertonic saline. The therapeutic intervention consisted in the administration of inhaled nitric oxide (iNO), as rescue therapy for refractory hypoxemia. Each patient underwent two 15-min steps at 0 and 20 ppm iNO, respectively. At each step, respiratory, gas exchange, and hemodynamic parameters were recorded, and V/Q distribution was measured, with unchanged ventilatory settings.</p></div><div><h3>Results</h3><p>Ten 65 [56–75] years old patients with moderate (40%) and severe (60%) ARDS were studied 10 [4-20] days after intubation. Gas exchange improved at 20 ppm iNO (PaO<sub>2</sub>/FiO<sub>2</sub> from 86 ± 16 to 110 ± 30 mmHg, p = 0.001; venous admixture from 51 ± 8 to 45 ± 7%, p = 0.0045; dead space from 29 ± 8 to 25 ± 6%, p = 0.008). The respiratory system's elastic properties and ventilation distribution were unaltered by iNO. Hemodynamics did not change after gas initiation (cardiac output 7.6 ± 1.9 <em>vs.</em> 7.7 ± 1.9 L/min, p = 0.66). The EIT pixel perfusion maps showed a variety of patterns of changes in pulmonary blood flow, whose increase positively correlated with PaO<sub>2</sub>/FiO<sub>2</sub> increase (R<sup>2</sup> = 0.50, p = 0.049).</p></div><div><h3>Conclusions</h3><p>The assessment of lung perfusion is feasible at the bedside and blood distribution can be modulated with effects that are visualized <em>in vivo</em>. These findings might lay the foundations for testing new therapies aimed at optimizing the regional perfusion in the lungs.</p></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9714206","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}