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S-nitrosylation therapy to improve oxygen delivery of banked blood.

ABSTRACT: From the perspectives of disease transmission and sterility maintenance, the world's blood supplies are generally safe. However, in multiple clinical settings, red blood cell (RBC) transfusions are associated with adverse cardiovascular events and multiorgan injury. Because ?85 million units of blood are administered worldwide each year, transfusion-related morbidity and mortality is a major public health concern. Blood undergoes multiple biochemical changes during storage, but the relevance of these changes to unfavorable outcomes is unclear. Banked blood shows reduced levels of S-nitrosohemoglobin (SNO-Hb), which in turn impairs the ability of stored RBCs to effect hypoxic vasodilation. We therefore reasoned that transfusion of SNO-Hb-deficient blood may exacerbate, rather than correct, impairments in tissue oxygenation, and that restoration of SNO-Hb levels would improve transfusion efficacy. Notably in mice, administration of banked RBCs decreased skeletal muscle pO2, but infusion of renitrosylated cells maintained tissue oxygenation. In rats, hemorrhage-induced reductions in muscle pO2 were corrected by SNO-Hb-repleted RBCs, but not by control, stored RBCs. In anemic awake sheep, stored renitrosylated, but not control RBCs, produced sustained improvements in O2 delivery; in anesthetized sheep, decrements in hemodynamic status, renal blood flow, and kidney function incurred following transfusion of banked blood were also prevented by renitrosylation. Collectively, our findings lend support to the idea that transfusions may be causally linked to ischemic events and suggest a simple approach to prevention (i.e., SNO-Hb repletion). If these data are replicated in clinical trials, renitrosylation therapy could have significant therapeutic impact on the care of millions of patients.

SUBMITTER: Reynolds JD

PROVIDER: S-EPMC3710799 | biostudies-other | 2013 Jul

REPOSITORIES: biostudies-other

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S-nitrosylation therapy to improve oxygen delivery of banked blood.

Reynolds James D JD Bennett Kyla M KM Cina Anthony J AJ Diesen Diana L DL Henderson Matthew B MB Matto Faisal F Plante Andrew A Williamson Rachel A RA Zandinejad Keivan K Demchenko Ivan T IT Hess Douglas T DT Piantadosi Claude A CA Stamler Jonathan S JS

Proceedings of the National Academy of Sciences of the United States of America 20130624 28

From the perspectives of disease transmission and sterility maintenance, the world's blood supplies are generally safe. However, in multiple clinical settings, red blood cell (RBC) transfusions are associated with adverse cardiovascular events and multiorgan injury. Because ∼85 million units of blood are administered worldwide each year, transfusion-related morbidity and mortality is a major public health concern. Blood undergoes multiple biochemical changes during storage, but the relevance of ...[more]

PMID: 23798386

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Project description:Although mechanical ventilation is a life-saving intervention in patients suffering from respiratory failure, prolonged mechanical ventilation is often associated with numerous complications including problematic weaning. In contracting skeletal muscle, inadequate oxygen supply can limit oxidative phosphorylation resulting in muscular fatigue. However, whether prolonged mechanical ventilation results in decreased diaphragmatic blood flow and induces an oxygen supply-demand imbalance in the diaphragm remains unknown.We tested the hypothesis that prolonged controlled mechanical ventilation results in a time-dependent reduction in rat diaphragmatic blood flow and microvascular PO2 and that prolonged mechanical ventilation would diminish the diaphragm's ability to increase blood flow in response to muscular contractions.Compared to 30 mins of mechanical ventilation, 6 hrs of mechanical ventilation resulted in a 75% reduction in diaphragm blood flow (via radiolabeled microspheres), which did not occur in the intercostal muscle or high-oxidative hindlimb muscle (e.g., soleus). There was also a time-dependent decline in diaphragm microvascular PO2 (via phosphorescence quenching). Further, contrary to 30 mins of mechanical ventilation, 6 hrs of mechanical ventilation significantly compromised the diaphragm's ability to increase blood flow during electrically-induced contractions, which resulted in a ~80% reduction in diaphragm oxygen uptake. In contrast, 6 hrs of spontaneous breathing in anesthetized animals did not alter diaphragm blood flow or the ability to augment flow during electrically-induced contractions.These new and important findings reveal that prolonged mechanical ventilation results in a time-dependent decrease in the ability of the diaphragm to augment blood flow to match oxygen demand in response to contractile activity and could be a key contributing factor to difficult weaning. Although additional experiments are required to confirm, it is tempting to speculate that this ventilator-induced decline in diaphragmatic oxygenation could promote a hypoxia-induced generation of reactive oxygen species in diaphragm muscle fibers and contribute to ventilator-induced diaphragmatic atrophy and contractile dysfunction.

Project description:Objective: Lactate is often used as a surrogate marker of inappropriate oxygen delivery. It has been shown that hyperlactatemia is associated with worse clinical outcome in children after cardiac surgery. The purpose of this study is to evaluate the association of hyperlactatemia, low systemic oxygen delivery, and hyperglycemia, in children admitted to the pediatric critical care unit after cardiopulmonary bypass. Design: Secondary analysis of an observational cohort study. Setting: Tertiary pediatric critical care unit (PICU). Patients: Ninety-three patients, aged 6 months to 16 years, undergoing cardiac surgery with cardiopulmonary bypass. Interventions: None. Measurements and Main Results: Metabolic tests (blood glucose, lactate, lactate/pyruvate ratio, and ketones) and oxygen extraction (SaO2-SvO2) were performed before anesthesia, at the end of cardiopulmonary bypass, at PICU admission, and at 4 and 12 h after PICU admission. Four hours after PICU admission, 62% of the patients had hyperlactatemia (>2 mmol/L), of whom 55% had normal oxygen extraction (SaO2-SvO2 < 30%). There was no correlation between lactate and oxygen extraction (R = -0.09, p = 0.41) but there was a moderate correlation between lactate and blood glucose (R = 0.55, p < 0.001). Using a logistic regression model, hyperlactatemia at 4 h after PICU admission was independently associated with hyperglycemia (p = 0.007) and lactate/pyruvate ratio (p = 0.007) at the same timepoint, as well as with lactate at PICU admission (p = 0.002), but not with weight (p = 0.45), severity of the cardiac lesion (p = 0.85), duration of bypass (p = 0.16), or oxygen extraction, as evaluated by SaO2-SvO2 (p = 0.54). At 12 h after PICU admission, there was a very week correlation between lactate and blood glucose (R = 0.27, p = 0.007), but none between lactate and oxygen extraction (R = 0.13, p = 0.20). Conclusion: In children after cardiopulmonary bypass, lactates are not correlated with higher oxygen extraction, but are correlated with hyperglycemia, at both 4 and 12 h after PICU admission. Future research is warranted to better define this relationship.

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Project description:BackgroundTreating hypoxemia while meeting the soaring demands of oxygen can be a challenge during the COVID-19 pandemic.ObjectiveTo determine the efficacy of the surgical facemask and the double-trunk mask on top of the low-flow oxygen nasal cannula on arterial partial pressure of oxygen (PaO2) in hypoxemic COVID-19 patients.DesignRandomized controlled trial.ParticipantsHospitalized adults with COVID-19 and hypoxemia treated with the low-flow nasal cannula were enrolled between November 13, 2020, and March 05, 2021.InterventionsPatients were randomized in a 1:1:1 ratio to receive either the nasal cannula alone (control) or the nasal cannula covered by the surgical facemask or the double-trunk mask. Arterial blood gases were collected at baseline and 30 min after the use of each system. The oxygen output was adapted afterwards to retrieve the baseline pulse oxygen saturation. The final oxygen output value was recorded after another 30-min period.Main measuresThe primary outcome was the absolute change in PaO2. Secondary outcomes included changes in oxygen output, arterial partial pressure of carbon dioxide (PaCO2), vital parameters, and breathlessness.Key resultsArterial blood samples were successfully collected in 24/27 (8 per group) randomized patients. Compared to the nasal cannula alone, PaO2 increased with the surgical facemask (mean change: 20 mmHg, 95% CI: 0.7-38.8; P = .04) and with the double-trunk mask (mean change: 40 mmHg; 95% CI: 21-59; P < .001). Oxygen output was reduced when adding the surgical facemask (median reduction: 1.5 L/min [95% CI: 0.5-4.5], P < .001) or the double-trunk mask (median reduction: 3.3 L/min [95% CI: 2-5], P < .001). The double-trunk mask was associated with a PaCO2 increase of 2.4 mmHg ([95% CI: 0-4.7], P = .049). Neither mask influenced vital parameters or breathlessness.ConclusionsThe addition of the surgical facemask or the double-trunk mask above the nasal cannula improves arterial oxygenation and reduces oxygen consumption.

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S-nitrosylation therapy to improve oxygen delivery of banked blood.

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S-nitrosylation therapy to improve oxygen delivery of banked blood.

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