The partial pressure of carbon monoxide in human tissues calculated using a parallel capillary-tissue cylinder model

2018 ◽  
Vol 124 (3) ◽  
pp. 761-768 ◽  
Author(s):  
Ronald F. Coburn
Keyword(s):  
Carbon Monoxide ◽  
Heme Proteins ◽  
Toxic Effects ◽  
Human Tissues ◽  
Co Poisoning ◽  
Tissue Model ◽  
Future Studies ◽  
Cylinder Model ◽  
The Mean

Tissue PCOvalues have not been previously estimated under conditions where the blood carboxyhemoglobin % saturation ([COHb]) is at a normal level or increased. Tissue PCOvalues are not known for conditions when [COHb] is increased during CO therapy or during CO poisoning. Using a modified Krogh parallel capillary-tissue model, mean tissue PCOwas calculated for when [COHb] was 1, 5, 10, and 15% saturation, relevant to CO therapy, and 20, 30, and 40% saturation, relevant to CO poisoning. Calculations were made for the time during which CO was being inhaled, after cessation of CO uptake, and for different O2extractions from blood flowing in the model capillary. The T1/2of relevant CO reactions was used in these calculations. When the [COHb] increased to 5 to 10% saturation, mean tissue PCOvalues increased to 500 to 1,100% of values when the [COHb] was 1% saturation. When the [COHb] increased to 20 to 40% saturation, mean tissue PCOvalues increased to 2,300 to 5,700% of the 1% saturation value. Results indicate the utility of the modified Krogh model in furthering understanding the physiology of determinants of tissue PCOand should facilitate future studies of in vivo CO binding to different extravascular heme proteins during CO therapy and during CO poisoning.NEW & NOTEWORTHY Tissue PCOlevels resulting from carboxyhemoglobin concentrations achieved during CO therapy or during CO poisoning have not been previously estimated. Results published here show that at carboxyhemoglobin levels achieved during CO therapy there are 500 to 1,100% increases in mean tissue PCOvalues. With carboxyhemoglobin increases associated with toxic effects, there are 2,300 to 5,700% increases in the mean tissue PCO. These differences suggest a basis for understanding the therapeutic and toxic effects of CO.

scholarly journals A neuroglobin-based high-affinity ligand trap reverses carbon monoxide–induced mitochondrial poisoning

2020 ◽  
Vol 295 (19) ◽  
pp. 6357-6371 ◽  
Author(s):  
Jason J. Rose ◽  
Kaitlin A. Bocian ◽  
Qinzi Xu ◽  
Ling Wang ◽  
Anthony W. DeMartino ◽  
...  
Keyword(s):  
Carbon Monoxide ◽  
Mitochondrial Respiration ◽  
Oxygen Delivery ◽  
Oxygen Electrode ◽  
Heart Tissue ◽  
Tissue Respiration ◽  
Co Poisoning ◽  
Affinity Ligand

Carbon monoxide (CO) remains the most common cause of human poisoning. The consequences of CO poisoning include cardiac dysfunction, brain injury, and death. CO causes toxicity by binding to hemoglobin and by inhibiting mitochondrial cytochrome c oxidase (CcO), thereby decreasing oxygen delivery and inhibiting oxidative phosphorylation. We have recently developed a CO antidote based on human neuroglobin (Ngb-H64Q-CCC). This molecule enhances clearance of CO from red blood cells in vitro and in vivo. Herein, we tested whether Ngb-H64Q-CCC can also scavenge CO from CcO and attenuate CO-induced inhibition of mitochondrial respiration. Heart tissue from mice exposed to 3% CO exhibited a 42 ± 19% reduction in tissue respiration rate and a 33 ± 38% reduction in CcO activity compared with unexposed mice. Intravenous infusion of Ngb-H64Q-CCC restored respiration rates to that of control mice correlating with higher electron transport chain CcO activity in Ngb-H64Q-CCC–treated compared with PBS-treated, CO-poisoned mice. Further, using a Clark-type oxygen electrode, we measured isolated rat liver mitochondrial respiration in the presence and absence of saturating solutions of CO (160 μm) and nitric oxide (100 μm). Both CO and NO inhibited respiration, and treatment with Ngb-H64Q-CCC (100 and 50 μm, respectively) significantly reversed this inhibition. These results suggest that Ngb-H64Q-CCC mitigates CO toxicity by scavenging CO from carboxyhemoglobin, improving systemic oxygen delivery and reversing the inhibitory effects of CO on mitochondria. We conclude that Ngb-H64Q-CCC or other CO scavengers demonstrate potential as antidotes that reverse the clinical and molecular effects of CO poisoning.

scholarly journals A Novel H2O2 Generator for Tumor Chemotherapy-Enhanced CO Gas Therapy

2021 ◽  
Vol 11 ◽  
Author(s):  
Yang Li ◽  
Zeming Liu ◽  
Weng Zeng ◽  
Ziqi Wang ◽  
Chunping Liu ◽  
...  
Keyword(s):  
Carbon Monoxide ◽  
Controlled Release ◽  
Tumor Microenvironment ◽  
Tumor Site ◽  
Co Poisoning ◽  
Chemotherapy Agent ◽  
Manganese Carbonyl ◽  
Co Gas

Carbon monoxide (CO) gas therapy is a promising cancer treatment. However, gas delivery to the tumor site remains problematic. Proper tunable control of CO release in tumors is crucial to increasing the efficiency of CO treatment and reducing the risk of CO poisoning. To overcome such challenges, we designed ZCM, a novel stable nanotechnology delivery system comprising manganese carbonyl (MnCO) combined with anticancer drug camptothecin (CPT) loaded onto a zeolitic imidazole framework-8 (ZIF-8). After intravenous injection, ZCM gradually accumulates in cancerous tissues, decomposing in the acidic tumor microenvironment, releasing CPT and MnCO. CPT acts as a chemotherapy agent destroying tumors and producing copious H2O2. MnCO can react with the H2O2 to generate CO, powerfully damaging the tumor. Both in vitro and in vivo experiments indicate that the ZCM system is both safe and has excellent tumor inhibition properties. ZCM is a novel system for CO controlled release, with significant potential to improve future cancer therapy.

Phototherapy and extracorporeal membrane oxygenation facilitate removal of carbon monoxide in rats

2019 ◽  
Vol 11 (513) ◽  
pp. eaau4217
Author(s):  
Luca Zazzeron ◽  
Anna Fischbach ◽  
Walfre Franco ◽  
William A. Farinelli ◽  
Fumito Ichinose ◽  
...  
Keyword(s):  
Carbon Monoxide ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Visible Light ◽  
Smoke Inhalation ◽  
Co Poisoning ◽  
Membrane Oxygenator ◽  
Injury Treatment ◽  
Further Development

Inhaled carbon monoxide (CO) displaces oxygen from hemoglobin, reducing the capacity of blood to carry oxygen. Current treatments for CO-poisoned patients involve administration of 100% oxygen; however, when CO poisoning is associated with acute lung injury secondary to smoke inhalation, burns, or trauma, breathing 100% oxygen may be ineffective. Visible light dissociates CO from hemoglobin. We hypothesized that the exposure of blood to visible light while passing through a membrane oxygenator would increase the rate of CO elimination in vivo. We developed a membrane oxygenator with optimal characteristics to facilitate exposure of blood to visible light and tested the device in a rat model of CO poisoning, with or without concomitant lung injury. Compared to ventilation with 100% oxygen, the addition of extracorporeal removal of CO with phototherapy (ECCOR-P) doubled the rate of CO elimination in CO-poisoned rats with normal lungs. In CO-poisoned rats with acute lung injury, treatment with ECCOR-P increased the rate of CO removal by threefold compared to ventilation with 100% oxygen alone and was associated with improved survival. Further development and adaptation of this extracorporeal CO photo-removal device for clinical use may provide additional benefits for CO-poisoned patients, especially for those with concurrent acute lung injury.

Derangement of PaCO2 requires physician attention in acute carbon monoxide poisoning

2020 ◽  
Vol 39 (5) ◽  
pp. 642-652
Author(s):  
JM Moon ◽  
BJ Chun ◽  
YS Cho
Keyword(s):  
Carbon Monoxide ◽  
Incidence Rate ◽  
Linear Trend ◽  
Carbon Monoxide Poisoning ◽  
Metabolic Changes ◽  
Secondary Response ◽  
Co Poisoning ◽  
Significant Linear Trend ◽  
Arterial Blood ◽  
The Mean

The objective was to describe the prevalence of derangement of the partial pressure of arterial carbon dioxide (PaCO2) and to determine the association between PaCO2 and adverse cardiovascular events (ACVEs) in carbon monoxide (CO)-poisoned patients. Additionally, we evaluated whether the derangement of PaCO2 was simply secondary to metabolic changes. This retrospective study included 194 self-breathing patients after CO poisoning with an indication for hyperbaric oxygen therapy and available arterial blood gas analysis at presentation and 6 h later. The incidence rate of hypocapnia at presentation after acute CO poisoning was 67.5%, and the mean PaCO2 during the first 6 h was 33 (31–36.7) mmHg. The most common acid–base imbalance in 131 patients with hypocapnia was primary respiratory alkalosis. The incidence rate of ACVEs during hospitalization was 50.5%. A significant linear trend in the incidence of ACVEs was observed across the total range of PaCO2 variables. In multivariate regression analysis, mean PaCO2 was independently associated with ACVEs (odds ratio 0.051; 95% confidence interval 0.004–0.632). PaCO2 derangements were common after acute CO poisoning and were not explainable as a mere secondary response to metabolic changes. The mean PaCO2 during the first 6 h was associated with ACVEs. Given the high incidence of ACVEs and PaCO2 derangement and the observed association between the mean PaCO2 and ACVEs, this study suggests that (1) PaCO2 should be monitored in the acute stage to predict and/or prevent ACVEs and (2) further investigation is needed to validate this result and explore the early manipulation of PaCO2 as a treatment strategy.

scholarly journals Evaluation of a fully automated end-tidal carbon monoxide instrument for breath analysis

1996 ◽  
Vol 42 (1) ◽  
pp. 50-56 ◽  
Author(s):  
H J Vreman ◽  
L M Baxter ◽  
R T Stone ◽  
D K Stevenson
Keyword(s):  
Carbon Monoxide ◽  
Sampling Efficiency ◽  
Excellent Correlation ◽  
Breath Sampling ◽  
Total Hemoglobin ◽  
In Vivo Tests ◽  
Term Newborns ◽  
The Mean ◽  
End Tidal

Abstract We evaluated a novel, portable breath sampler/CO-quantifying instrument [Baby's Breath Carbon Monoxide Analyzer (BB); Natus Medical], developed for use at the bedside or with gas samples collected into bags. Bench tests demonstrated that the CO measurements were linear, accurate, and precise when compared with gas chromatography (GC) results. In vivo tests (n = 30) performed with adults showed excellent correlation between end-tidal breath CO measurements (ETCO) corrected for inhaled CO (ETCOc) as determined by BB and GC. Breath sampling efficiency was 96%. ETCOc measurements and blood carboxyhemoglobin fractions (% of total hemoglobin) corrected for inhaled CO (COHbc) correlated strongly: COHbc = 0.25 ETCOc--0.01 microL/L CO (r2 = 0.97, Sy/x = 0.47, SE slope = 0.01, n = 30). The imprecision, assessed by the mean of the population's CV for triplicate determinations, was 11%. Measurements with healthy and hemolytic term newborns showed that ETCOc values of > 3 microL/L correlated with known hemolytic conditions. We conclude that this instrument is clinically reliable and can be used to noninvasively measure ETCO in neonates and adults.

S-100β in predicting the need of hyperbaric oxygen in CO-induced delayed neurological sequels

2019 ◽  
Vol 39 (5) ◽  
pp. 614-623
Author(s):  
Amal SAF Hafez ◽  
Ghada N El-Sarnagawy
Keyword(s):  
Carbon Monoxide ◽  
Hyperbaric Oxygen ◽  
Operating Characteristic ◽  
Characteristic Curve ◽  
Area Under The Curve ◽  
Curve Analysis ◽  
Co Poisoning ◽  
Cutoff Value ◽  
The Mean ◽  
Operating Characteristic Curve

Background: Delayed neurological sequels (DNS) have been described after carbon monoxide (CO) poisoning. There is a need to find a new prognostic marker to guide the use of hyperbaric oxygen (HBO) therapy. Aim: To evaluate serum S-100β level in patients presenting with acute CO poisoning as an indicator of poisoning severity and predictor of DNS occurrence and HBO need in those patients. Methods: This prospective cohort study included patients with acute CO poisoning. On admission, carboxyhemoglobin (COHb) and S-100β levels were measured. Patients were followed up for 6 months for signs of DNS. Results: Out of 50 patients, 6 only developed DNS. The mean of S-100β levels was significantly higher in patients with severe poisoning and those with DNS. Receiver operating characteristic curve analysis revealed that S-100β had an area under the curve 0. 871; at a cutoff value ≥ 0.67 µg/L, its sensitivity and specificity were 100% and 77.3%, respectively. The sensitivity of S-100β was significantly higher than that of COHb, while its specificity and overall accuracy were significantly higher than those of HBO criteria. Conclusion: Serum S-100β level on admission could be a marker of poisoning severity and a predictor of CO-induced DNS development that guides the use of HBO therapy.

scholarly journals Ex vivo use of cell-permeable succinate prodrug attenuates mitochondrial dysfunction in blood cells obtained from carbon monoxide-poisoned individuals

2020 ◽  
Vol 319 (1) ◽  
pp. C129-C135 ◽  
Author(s):  
Shawn Owiredu ◽  
Abhay Ranganathan ◽  
David M. Eckmann ◽  
Frances S. Shofer ◽  
Kevin Hardy ◽  
...  
Keyword(s):  
Carbon Monoxide ◽  
Blood Cells ◽  
Mononuclear Cells ◽  
Ex Vivo ◽  
Mitochondrial Dynamics ◽  
Control Group ◽  
Co Poisoning ◽  
Peripheral Blood Mononuclear ◽  
Complex Ii

The purpose of this study was to evaluate a new pharmacological strategy using a first-generation succinate prodrug, NV118, in peripheral blood mononuclear cells (PBMCs) obtained from subjects with carbon monoxide (CO) poisoning and healthy controls. We obtained human blood cells from subjects with CO poisoning and healthy control subjects. Intact PBMCs from subjects in the CO and Control group were analyzed with high-resolution respirometry measured in pmol O2 per second per 10−6 PBMCs. In addition to obtaining baseline respiration, NV118 (100 μM) was injected, and the same parameters of respiration were obtained for comparison in PBMCs. We measured mitochondrial dynamics with microscopy with the same conditions. We enrolled 37 patients (17 in the CO group and 20 in the Control group for comparison) in the study. PMBCs obtained from subjects in the CO group had overall significantly lower respiration compared with the Control group ( P < 0.0001). There was a significant increase in respiration with NV118, specifically with an increase in maximum respiration and respiration from complex II and complex IV ( P < 0.0001). The mitochondria in PBMCs demonstrated an overall increase in net movement compared with the Control group. Our results of this study suggest that the therapeutic compound, NV118, increases respiration at complex II and IV as well as restoration of mitochondrial movement in PBMCs obtained from subjects with CO poisoning. Mitochondrial-directed therapy offers a potential future strategy with further exploration in vivo.

Abstract 183: Carbon Monoxide Induces Macrophage VEGF Production and Promotes Angiogenic Behavior in Endothelial Cells

2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Andrew E Leake ◽  
Guiying Hong ◽  
Christopher B Washington ◽  
Ankur J Shukla ◽  
Ulka Sachdev ◽  
...  
Keyword(s):  
Carbon Monoxide ◽  
Umbilical Vein ◽  
Fold Increase ◽  
Peritoneal Macrophages ◽  
Phenotypic Change ◽  
Enos Expression ◽  
Future Studies ◽  
Angiogenic Effect

Introduction: Carbon monoxide (CO) has potent anti-inflammatory and pro-healing properties. We have previously shown that CO enhances endothelial cell (EC) angiogenic behavior in vitro. More striking, however, is that conditioned medium (CM) from macrophages isolated from CO treated rats can promote angiogenesis indirectly. We sought to examine the mechanism of this indirect angiogenic effect of CO. Methods: Peritoneal macrophages were collected from rats after inhaled CO treatment (250 PPM for 1 hr) or air treatment. Macrophages were cultured overnight and CM was collected to treat human umbilical vein ECs (HUVECs). VEGF and eNOS expression was assessed by Western blot. Results: CM from macrophages isolated from CO treated rats (CO) showed a 3-fold increase in VEGF vs Air CM (Ratio CO/Air=2.96, Range 1.6-4.2) (Figure). VEGF levels were similar between the macrophages from CO or air treated rats (CO/Air=0.89). HUVECs treated with CO or Air CM also showed no difference in VEGF levels (CO/Air=1.07). However, eNOS expression was significantly increased in HUVECs treated with CO CM vs. Air CM (CO/Air=26.4, Range 20-32; p=0.004). HUVECs cultured in a CO chamber or a standard incubator exhibited no change in eNOS expression (CO/Air, 1.38 p=0.11). Conclusion: In vivo CO promotes macrophage secretion of VEGF. These cells can promote angiogenic behavior in ECs through this VEGF and other secreted products. These macrophage products upregulate eNOS but not VEGF expression in HUVECs. The effect of the CO CM on eNOS expression in HUVECs could not be reproduced by direct CO treatment of the cells. Future studies will further characterize the phenotypic change of the macrophages induced by inhaled CO that favors angiogenesis and healing.

Effects of NO-Donors on Thrombus Formation and Microcirculation in Cerebral Vessels of the Rat

1996 ◽  
Vol 76 (01) ◽  
pp. 111-117 ◽  
Author(s):  
Yasuto Sasaki ◽  
Junji Seki ◽  
John C Giddings ◽  
Junichiro Yamamoto
Keyword(s):  
Blood Flow ◽  
Thrombus Formation ◽  
Dependent Manner ◽  
Red Cell ◽  
Cell Velocity ◽  
Red Cell Velocity ◽  
The Mean ◽  
Wall Shear ◽  
Dose Dependent

SummarySodium nitroprusside (SNP) and 3-morpholinosydnonimine (SIN-1), are known to liberate nitric oxide (NO). In this study the effects of SNP and SIN-1 on thrombus formation in rat cerebral arterioles and venules in vivo were assessed using a helium-neon (He-Ne) laser. SNP infused at doses from 10 Μg/kg/h significantly inhibited thrombus formation in a dose dependent manner. This inhibition of thrombus formation was suppressed by methylene blue. SIN-1 at a dose of 100 Μg/kg/h also demonstrated a significant antithrombotic effect. Moreover, treatment with SNP increased vessel diameter in a dose dependent manner and enhanced the mean red cell velocity measured with a fiber-optic laser-Doppler anemometer microscope (FLDAM). Blood flow, calculated from the mean red cell velocity and vessel diameters was increased significantly during infusion. In contrast, mean wall shear rates in the arterioles and venules were not changed by SNP infusion. The results indicated that SNP and SIN-1 possessed potent antithrombotic activities, whilst SNP increased cerebral blood flow without changing wall shear rate. The findings suggest that the NO released by SNP and SIN-1 may be beneficial for the treatment and protection of cerebral infarction

Influence of Platelet Membrane Sialic Acid and Platelet-Associated IgG on Ageing and Sequestration of Blood Platelets in Baboons

1993 ◽  
Vol 70 (04) ◽  
pp. 676-680 ◽  
Author(s):  
H F Kotzé ◽  
V van Wyk ◽  
P N Badenhorst ◽  
A du P Heyns ◽  
J P Roodt ◽  
...  
Keyword(s):  
Sialic Acid ◽  
Life Span ◽  
Blood Platelets ◽  
Senescent Cell ◽  
Platelet Membrane ◽  
Antigen Complex ◽  
The Mean ◽  
Aggregation Of Platelets

SummaryPlatelets were isolated from blood of baboons and treated with neuraminidase to remove platelet membrane sialic acid, a process which artificially ages the platelets. The platelets were then labelled with 111In and their mean life span, in vivo distribution and sites of Sequestration were measured. The effect of removal of sialic acid on the attachment of immunoglobulin to platelets were investigated and related to the Sequestration of the platelets by the spleen, liver, and bone marrow. Removal of sialic acid by neuraminidase did not affect the aggregation of platelets by agonists in vitro, nor their sites of Sequestration. The removal of 0.51 (median, range 0.01 to 2.10) nmol sialic acid/108 platelets shortened their life span by 75 h (median, range 0 to 132) h (n = 19, p <0.001), and there was an exponential correlation between the shortening of the mean platelet life span and the amount of sialic acid removed. The increase in platelet-associated IgG was 0.112 (median, range 0.007 to 0.309) fg/platelet (n = 25, p <0.001) after 0.79 (median, range 0.00 to 6.70) nmol sialic acid/108 platelets was removed (p <0.001). There was an exponential correlation between the shortening of mean platelet life span after the removal of sialic acid and the increase in platelet-associated IgG. The results suggest that platelet membrane sialic acid influences ageing of circulating platelets, and that the loss of sialic acid may have exposed a senescent cell antigen that binds IgG on the platelet membrane. The antibody-antigen complex may then provide a signal to the macrophages that the platelet is old, and can be phagocytosed and destroyed.

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