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array:24 [ "pii" => "S217357272400170X" "issn" => "21735727" "doi" => "10.1016/j.medine.2024.06.016" "estado" => "S300" "fechaPublicacion" => "2024-09-01" "aid" => "2062" "copyright" => "Elsevier España, S.L.U. and SEMICYUC" "copyrightAnyo" => "2024" "documento" => "article" "crossmark" => 1 "subdocumento" => "sco" "cita" => "Med Intensiva. 2024;48:543-5" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "Traduccion" => array:1 [ "en" => array:19 [ "pii" => "S0210569124002341" "issn" => "02105691" "doi" => "10.1016/j.medin.2024.06.006" "estado" => "S300" "fechaPublicacion" => "2024-09-01" "aid" => "2062" "copyright" => "Elsevier España, S.L.U. y SEMICYUC" "documento" => "article" "crossmark" => 1 "subdocumento" => "sco" "cita" => "Med Intensiva. 2024;48:543-5" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "en" => array:11 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Point of view</span>" "titulo" => "Nitric oxide as the third respiratory gas. A new opportunity to revisit the use of oxygen therapy in clinical practice" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "543" "paginaFinal" => "545" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Óxido nítrico como tercer gas respiratorio. 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Right (Hb in blue): upon reaching hypoxic tissues, Hb will cooperatively release oxygen molecules during transition to the deoxygenated state. Liberation of oxygen also causes the transfer of SNO from deoxygenated Hb to other erythrocyte thiols (R-S-H) and ultimately shuttling SNO out of red blood cells. Thus, Hb deoxygenation in tissues will lead to vasorelaxation (SNO-mediated vasodilation). Adapted from reference 6, with permission.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "José Manuel Valencia-Gallardo, Felipe Rodríguez de Castro, Jordi Solé-Violán, José Carlos Rodríguez-Gallego" "autores" => array:4 [ 0 => array:2 [ "nombre" => "José Manuel" "apellidos" => "Valencia-Gallardo" ] 1 => array:2 [ "nombre" => "Felipe" "apellidos" => "Rodríguez de Castro" ] 2 => array:2 [ "nombre" => "Jordi" "apellidos" => "Solé-Violán" ] 3 => array:2 [ "nombre" => "José" "apellidos" => "Carlos Rodríguez-Gallego" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S217357272400170X" "doi" => "10.1016/j.medine.2024.06.016" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S217357272400170X?idApp=WMIE" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0210569124002341?idApp=WMIE" "url" => "/02105691/0000004800000009/v1_202408290622/S0210569124002341/v1_202408290622/en/main.assets" ] ] "itemSiguiente" => array:19 [ "pii" => "S2173572724001978" "issn" => "21735727" "doi" => "10.1016/j.medine.2024.04.018" "estado" => "S300" "fechaPublicacion" => "2024-09-01" "aid" => "2027" "copyright" => "Elsevier España, S.L.U. and SEMICYUC" "documento" => "article" "crossmark" => 1 "subdocumento" => "crp" "cita" => "Med Intensiva. 2024;48:546-8" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "en" => array:10 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Scientific Letter</span>" "titulo" => "Acute respiratory distress syndrome at high altitude: Considerations for diagnosis and treatment" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "546" "paginaFinal" => "548" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Síndrome de distrés respiratorio agudo en la altitud: consideraciones sobre el diagnóstico y tratamiento" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Adrián Avila-Hilari, Amilcar Tinoco-Solórzano, Jorge Vélez-Páez, Daniel Molano Franco, Felipe de Jesús Montelongo, Manuel Luis Avellanas-Chavala" "autores" => array:6 [ 0 => array:2 [ "nombre" => "Adrián" "apellidos" => "Avila-Hilari" ] 1 => array:2 [ "nombre" => "Amilcar" "apellidos" => "Tinoco-Solórzano" ] 2 => array:2 [ "nombre" => "Jorge" "apellidos" => "Vélez-Páez" ] 3 => array:2 [ "nombre" => "Daniel" "apellidos" => "Molano Franco" ] 4 => array:2 [ "nombre" => "Felipe de Jesús" "apellidos" => "Montelongo" ] 5 => array:2 [ "nombre" => "Manuel Luis" "apellidos" => "Avellanas-Chavala" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0210569124001438" "doi" => "10.1016/j.medin.2024.04.006" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0210569124001438?idApp=WMIE" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173572724001978?idApp=WMIE" "url" => "/21735727/0000004800000009/v1_202409021221/S2173572724001978/v1_202409021221/en/main.assets" ] "itemAnterior" => array:19 [ "pii" => "S2173572724001735" "issn" => "21735727" "doi" => "10.1016/j.medine.2024.06.019" "estado" => "S300" "fechaPublicacion" => "2024-09-01" "aid" => "2041" "copyright" => "Elsevier España, S.L.U. and SEMICYUC" "documento" => "article" "crossmark" => 1 "subdocumento" => "sco" "cita" => "Med Intensiva. 2024;48:528-42" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Update in intensive care medicine: ultrasound in the critically ill patient. 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Pulmonary artery acceleration time (Tac). E. Pulsed Doppler recording of pulmonary insufficiency. The arrows indicate the protodiastolic maximum velocity of the pulmonary insufficiency flow (V<span class="elsevierStyleInf">PIed</span>) and the end-diastolic maximum velocity of the pulmonary insufficiency flow (V<span class="elsevierStyleInf">PIed</span>). F. Normal type I pulmonary artery flow with symmetrical ascent and descent. G. Type I pulmonary artery flow with symmetrical triangular follow, normal flow. H. Type II pulmonary artery flow with asymmetrical triangular follow, suggestive of increased pulmonary pressure. I. Type III pulmonary artery flow with an arrow indicating the mesosystolic notch due to early closure of the pulmonary valve.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Virginia Fraile-Gutiérrez, Lluis Zapata-Fenor, Aaron Blandino-Ortiz, Manuel Guerrero-Mier, Ana Ochagavia-Calvo" "autores" => array:5 [ 0 => array:2 [ "nombre" => "Virginia" "apellidos" => "Fraile-Gutiérrez" ] 1 => array:2 [ "nombre" => "Lluis" "apellidos" => "Zapata-Fenor" ] 2 => array:2 [ "nombre" => "Aaron" "apellidos" => "Blandino-Ortiz" ] 3 => array:2 [ "nombre" => "Manuel" "apellidos" => "Guerrero-Mier" ] 4 => array:2 [ "nombre" => "Ana" "apellidos" => "Ochagavia-Calvo" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0210569124002110" "doi" => "10.1016/j.medin.2024.05.008" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0210569124002110?idApp=WMIE" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173572724001735?idApp=WMIE" "url" => "/21735727/0000004800000009/v1_202409021221/S2173572724001735/v1_202409021221/en/main.assets" ] "en" => array:15 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Point of view</span>" "titulo" => "Nitric oxide as the third respiratory gas. A new opportunity to revisit the use of oxygen therapy in clinical practice" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "543" "paginaFinal" => "545" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "José Manuel Valencia-Gallardo, Felipe Rodríguez de Castro, Jordi Solé-Violán, José Carlos Rodríguez-Gallego" "autores" => array:4 [ 0 => array:4 [ "nombre" => "José Manuel" "apellidos" => "Valencia-Gallardo" "email" => array:1 [ 0 => "jvalgal@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Felipe" "apellidos" => "Rodríguez de Castro" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "Jordi" "apellidos" => "Solé-Violán" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] 3 => array:3 [ "nombre" => "José" "apellidos" => "Carlos Rodríguez-Gallego" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "aff0020" ] ] ] ] "afiliaciones" => array:4 [ 0 => array:3 [ "entidad" => "Department of Respiratory Medicine, Hospital Universitario de Gran Canaria Dr. Negrín, Las Palmas de Gran Canaria, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Professor of Medicine, Department of Medical and Surgical Sciences, School of Medicine, University of Las Palmas de Gran Canaria, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Intensive Care Unit, Hospital Universitario de Gran Canaria Dr. Negrín, Las Palmas de Gran Canaria, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Department of Immunology, Hospital Universitario de Gran Canaria Dr. Negrín, Las Palmas de Gran Canaria, Spain" "etiqueta" => "d" "identificador" => "aff0020" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Óxido nítrico como tercer gas respiratorio. Una nueva ocasión para revisar el empleo de oxigenoterapia en la práctica clínica" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1346 "Ancho" => 2508 "Tamanyo" => 287674 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Allosteric linkage of Hb conformation to O<span class="elsevierStyleInf">2</span> and SNO release. Left (Hb in red): cooperativity leads to Hb in the lung being able to bind oxygen molecules. Oxygenated Hb will also bind and stabilize SNO at Hb. Right (Hb in blue): upon reaching hypoxic tissues, Hb will cooperatively release oxygen molecules during transition to the deoxygenated state. Liberation of oxygen also causes the transfer of SNO from deoxygenated Hb to other erythrocyte thiols (R-S-H) and ultimately shuttling SNO out of red blood cells. Thus, Hb deoxygenation in tissues will lead to vasorelaxation (SNO-mediated vasodilation). Adapted from reference 6, with permission.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">New drug development requires accurate evaluation of efficacy and understanding of the underlying physiology.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Old therapies, as oxygen therapy, should not be exempt from such demands. We have now the opportunity to consider a more rational use of oxygen therapy in clinical practice<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> focusing on the role of hemoglobin in improving oxygen delivery to tissues.</p><p id="par0010" class="elsevierStylePara elsevierViewall">Almost twenty years ago, McNulty and colleagues<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> demonstrated that in patients with stable coronary artery disease, administration of 100% oxygen increased coronary vascular resistance and reduced coronary blood flow compared to breathing room air. This increase in vascular resistance could be explained by the oxidative degradation of endothelial nitric oxide (NO) caused by reactive oxygen species generated under hyperoxic conditions.</p><p id="par0015" class="elsevierStylePara elsevierViewall">Moreover, there is strong evidence that NO bioactivity is not restricted to the vascular endothelium. Hemoglobin can also incorporate stable metabolites of NO into the red blood cell (RBCs) environment.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> In pulmonary circulation, oxygenation of Hb facilitates NO uptake to form S-nitrosohemoglobin (SNO-Hb) while, in the peripheral circulation, deoxygenation facilitates the transfer of S-nitrosothiols (SNOs) out of RBCs.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Since SNOs promote vasodilation, the release of NO from Hb to a hypoxic environment result in increased blood flow to hypoxic tissues and would explain the physiological significance of SNO-Hb improving tissue oxygenation (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> In other words, the bioavailability of NO in vivo could be directly and effectively coupled to the oxygen saturation of Hb, not PO<span class="elsevierStyleInf">2</span>, so oxyhemoglobin (SaO<span class="elsevierStyleInf">2</span>) would establish a dynamic regulation of oxygenated blood flow in the microcirculation.<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4–6</span></a> This complementary activity of Hb provides a more efficient interpretation of its function. Rather than being considered a mere “transporter”, Hb would now ensure an optimal tissue oxygen supply.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">This alternative interpretation of the Hb role would promote the implementation of a targeted oxygenation with potential implications in clinical practice. In this regard, a judicious use of oxygen therapy would prevent the toxic effects of hyperoxia<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> and focus the clinician's concern on maintaining a SaO<span class="elsevierStyleInf">2</span> value within a safety range.</p><p id="par0030" class="elsevierStylePara elsevierViewall">As a result, two remarks should be taken account:<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">1</span><p id="par0035" class="elsevierStylePara elsevierViewall">SaO<span class="elsevierStyleInf">2</span> target of 100% should be avoided. Hemoglobin releases SNOs as blood becomes deoxygenated.<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5,6</span></a> Therefore, a SaO<span class="elsevierStyleInf">2</span> value far from 100% would preserve the vasodilator function of partial Hb deoxygenation.</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">2</span><p id="par0040" class="elsevierStylePara elsevierViewall">The upper inflection point in the oxygen hemoglobin dissociation curve would represent the nadir in the optimal supply of O<span class="elsevierStyleInf">2</span>. Consequently, a SaO<span class="elsevierStyleInf">2</span> value closer to 90% could be a safe threshold. Ideal SaO<span class="elsevierStyleInf">2</span> have not been precisely established and may vary depending on clinical features,<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> but in terms of adverse outcomes, recent randomized clinical trials have demonstrated no superiority of maintaining higher values of SaO<span class="elsevierStyleInf">2,</span> and even fewer complications with the use of more restrictive oxygen therapy strategy among critically ill patients.<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8,9</span></a> It is important to remember that not only PaO<span class="elsevierStyleInf">2</span> is almost irrelevant in oxygen delivery (DO<span class="elsevierStyleInf">2</span>) to the tissues but also high PaO<span class="elsevierStyleInf">2</span> values could increase mortality.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a></p></li></ul></p><p id="par0045" class="elsevierStylePara elsevierViewall">In addition, to ensure adequate tissue oxygenation, a sufficient Hb level must be maintained. As with SaO<span class="elsevierStyleInf">2</span>, determining the optimal Hb level in specific clinical scenarios has been the goal of several guidelines<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">11,12</span></a> but discussion of this topic is beyond the scope of this paper. In any case, the decision to administer a blood transfusion should be based on clinical judgement of the individual's risk/benefit ratio, including risks associated with anemia and transfusion.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">All of the above would be consistent arguments for promoting automatic titration systems for oxygen therapy at bedside. Although it is a not widely implemented monitoring procedure, initial findings suggest an improvement in controlling target SO<span class="elsevierStyleInf">2</span> compared with manual titration and could improve morbidity and mortality and reduce care costs.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">In short, scientific evidence supports a vasoactive role of Hb that would make it possible to better appreciate the tissue oxygenation optimizing function of Hb; it could also reinforce the prudent use of oxygen therapy if NO is considered as the third respiratory gas.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Author contributions</span><p id="par0060" class="elsevierStylePara elsevierViewall">Conception and design: J.M. Valencia-Gallardo, F. Rodríguez -de Castro, J. Solé-Violán, J.C. Rodríguez-Gallego.</p><p id="par0065" class="elsevierStylePara elsevierViewall">Collection, analysis and interpretation of the data: J.M. Valencia-Gallardo, F. Rodríguez de Castro, J. Solé-Violán, J.C. Rodríguez-Gallego.</p><p id="par0070" class="elsevierStylePara elsevierViewall">Final approval of the article: J.M. Valencia-Gallardo, F. Rodríguez de Castro, J. Solé-Violán, J.C. Rodríguez-Gallego.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Financial support</span><p id="par0075" class="elsevierStylePara elsevierViewall">This work is unfunded.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Disclosures</span><p id="par0080" class="elsevierStylePara elsevierViewall">Authors have disclosed no conflicts of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:5 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Author contributions" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "Financial support" ] 2 => array:2 [ "identificador" => "sec0015" "titulo" => "Disclosures" ] 3 => array:2 [ "identificador" => "xack770309" "titulo" => "Acknowledgment" ] 4 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "multimedia" => array:1 [ 0 => array:8 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1346 "Ancho" => 2508 "Tamanyo" => 287674 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Allosteric linkage of Hb conformation to O<span class="elsevierStyleInf">2</span> and SNO release. Left (Hb in red): cooperativity leads to Hb in the lung being able to bind oxygen molecules. Oxygenated Hb will also bind and stabilize SNO at Hb. Right (Hb in blue): upon reaching hypoxic tissues, Hb will cooperatively release oxygen molecules during transition to the deoxygenated state. Liberation of oxygen also causes the transfer of SNO from deoxygenated Hb to other erythrocyte thiols (R-S-H) and ultimately shuttling SNO out of red blood cells. Thus, Hb deoxygenation in tissues will lead to vasorelaxation (SNO-mediated vasodilation). Adapted from reference 6, with permission.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:12 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Oxygen delivery in the treatment of anemia" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "H.F. 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