Carbon monoxide (CO) poisoning affects 50,000 people a year in the United States. The clinical presentation runs a spectrum, ranging from headache and dizziness to coma and death, with a mortality ...rate ranging from 1 to 3%. A significant number of patients who survive CO poisoning suffer from long-term neurological and affective sequelae. The neurologic deficits do not necessarily correlate with blood CO levels but likely result from the pleiotropic effects of CO on cellular mitochondrial respiration, cellular energy utilization, inflammation, and free radical generation, especially in the brain and heart. Long-term neurocognitive deficits occur in 15-40% of patients, whereas approximately one-third of moderate to severely poisoned patients exhibit cardiac dysfunction, including arrhythmia, left ventricular systolic dysfunction, and myocardial infarction. Imaging studies reveal cerebral white matter hyperintensities, with delayed posthypoxic leukoencephalopathy or diffuse brain atrophy. Management of these patients requires the identification of accompanying drug ingestions, especially in the setting of intentional poisoning, fire-related toxic gas exposures, and inhalational injuries. Conventional therapy is limited to normobaric and hyperbaric oxygen, with no available antidotal therapy. Although hyperbaric oxygen significantly reduces the permanent neurological and affective effects of CO poisoning, a portion of survivors still have substantial morbidity. There has been some early success in therapies targeting the downstream inflammatory and oxidative effects of CO poisoning. New methods to directly target the toxic effect of CO, such as CO scavenging agents, are currently under development.
Carbon monoxide (CO) is increasingly recognized as a cell-signalling molecule akin to nitric oxide (NO). CO has attracted particular attention as a potential therapeutic agent because of its reported ...anti-hypertensive, anti-inflammatory and cell-protective effects. We discuss recent progress in identifying new effector systems and elucidating the mechanisms of action of CO on,
e.g.
, ion channels, as well as the design of novel methods to monitor CO in cellular environments. We also report on recent developments in the area of CO-releasing molecules (CORMs) and materials for controlled CO application. Novel triggers for CO release, metal carbonyls and degradation mechanisms of CORMs are highlighted. In addition, potential formulations of CORMs for targeted CO release are discussed.
Effector systems, sensing and controlled release of the biosignaling molecule carbon monoxide are featured.
The carbon monoxide (CO) in the marine boundary layer and in the surface waters and water column were measured along the western limb of the North Pacific from the Korean Peninsula to Alaska, USA, in ...summer 2012. The observation allows us to estimate the CO budgets in the surface mixed layer of the three distinct regimes: the East Sea (Sea of Japan) (ES), the Northwest Pacific (NP), and the Bering Sea (BS). CO photochemical production rates were 56(±15) µmol m.sup.-2 d.sup.-1, 27(±3) µmol m.sup.-2 d.sup.-1, and 26(±2) µmol m.sup.-2 d.sup.-1, while microbial consumption rates were 30(±8) µmol m.sup.-2 d.sup.-1, 24(±5) µmol m.sup.-2 d.sup.-1, and 63(±19) µmol m.sup.-2 d.sup.-1 in the ES, NP, and BS, respectively, both of which are the dominant components of the CO budget in the ocean. The other two known components, air-sea gas exchange and downward mixing, remained negligible (less than 3 µmol m.sup.-2 d.sup.-1) in all regimes. While the CO budget in the surface mixed layer of the NP was in balance, the CO production surpassed the consumption in the ES, and vice versa in the BS. The significant imbalances in the CO budget in the ES (25 ± 17 µmol m.sup.-2 d.sup.-1) and the BS (40 ± 19 µmol m.sup.-2 d.sup.-1) are suggested to be compensated by external physical transport such as lateral advection, subduction, or ventilation. Notably, the increase in the CO column burden correlated with the imbalance in the CO budget, highlighting the significant role of the physical transport in the marine CO cycles. Our observation, for the first time, underscores the potential importance of physical transport in driving CO dynamics in the marine environment.
Carbon monoxide (CO) is increasingly being accepted as a cytoprotective and homeostatic molecule with important signalling capabilities in physiological and pathophysiological situations. The ...endogenous production of CO occurs through the activity of constitutive (haem oxygenase 2) and inducible (haem oxygenase 1) haem oxygenases, enzymes that are responsible for the catabolism of haem. Through the generation of its products, which in addition to CO includes the bile pigments biliverdin, bilirubin and ferrous iron, the haem oxygenase 1 system also has an obligatory role in the regulation of the stress response and in cell adaptation to injury. This Review provides an overview of the physiology of CO, summarizes the effects of CO gas and CO-releasing molecules in preclinical animal models of cardiovascular disease, inflammatory disorders and organ transplantation, and discusses the development and therapeutic options for the exploitation of this simple gaseous molecule.
The toxicity of carbon monoxide has been recognized for long throughout history and is unquestionably the leading cause of unintentional poisoning deaths in the Western countries. The severity of ...poisoning is dependent upon environmental and human factor. The leading pathophysiological mechanism resides in the ability of carbon monoxide to bind to hemoglobin molecules with high affinity, displacing oxygen and generating carboxyhemoglobin, which is virtually ineffective to deliver oxygen to the tissues. The organs with the highest demand for oxygen such as the brain and the heart are more vulnerable to injury. Myocardial involvement is commonplace in moderate to severe carbon monoxide poisoning and is associated with a substantially higher risk of mortality. Besides hypoxic damage, carbon monoxide produces myocardium injuries with cardiospecific mechanisms, mostly attributable to direct damage at cellular or subcellular level. The clinical spectrum of heart involvement is broad and encompasses cardiomyopathy, angina attack, myocardial infarction, arrhythmias and heart failure up to myocardial stunning, cardiogenic shock and sudden death. Patients with underlying cardiac disease, especially coronary heart disease, are at greater risk of infarction and arrhythmias. Single photon emission computed tomography (SPECT) is the technique of choice for diagnosing cardiac involvement, whereas the recent introduction of the highly sensitive troponin immunoassays seems promising for the early triage of patients. No specific treatment other than oxygen delivery can be advocated for cardiac toxicity at present, and 100% oxygen therapy should be continued until the patient is asymptomatic and carboxyhemoglobin levels decrease below 5–10%.
►Carbon monoxide is the leading cause of unintentional poisoning. ►This compound binds to hemoglobin and reduces oxygen delivery to the tissues. ►Myocardial injury is also caused by specific cellular or subcellular mechanisms. ►Heart involvement includes cardiomyopathies, myocardial infarction, arrhythmias. ►Highly sensitive troponin immunoassays may be useful for early triage of patients.
Carbon monoxide (CO) is an endogenous small signalling molecule in the human body, produced by the action of haem oxygenase on haem. Since it is very difficult to apply safely as a gas, solid storage ...and delivery forms for CO are now explored. Most of these CO‐releasing molecules (CORMs) are based on the inactivation of the CO by coordinating it to a transition metal centre in a prodrug approach. After a brief look at the potential cellular target structures of CO, an overview of the design principles and activation mechanisms for CO release from a metal coordination sphere is given. Endogenous and exogenous triggers discussed include ligand exchange reactions with medium, enzymatically‐induced CO release and photoactivated liberation of CO. Furthermore, the attachment of CORMs to hard and soft nanomaterials to confer additional target specificity to such systems is critically assessed. A survey of analytical methods for the study of the stoichiometry and kinetics of CO release, as well as the tracking of CO in living systems by using fluorescent probes, concludes this review. CORMs are very valuable tools for studying CO bioactivity and might lead to new drug candidates; however, in the design of future generations of CORMs, particular attention has to be paid to their drug‐likeness and the tuning of the peripheral ‘drug sphere’ for specific biomedical applications. Further progress in this field will thus critically depend on a close interaction between synthetic chemists and researchers exploring the physiological effects and therapeutic applications of CO.
Linked Articles
This article is part of a themed section on Pharmacology of the Gasotransmitters. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-6
Carbon monoxide (CO) poisoning is common in modern society, resulting in significant morbidity and mortality in the United States annually. Over the past two decades, sufficient information has been ...published about carbon monoxide poisoning in the medical literature to draw firm conclusions about many aspects of the pathophysiology, diagnosis, and clinical management of the syndrome, along with evidence-based recommendations for optimal clinical practice. This article provides clinical practice guidance to the pulmonary and critical care community regarding the diagnosis, management, and prevention of acute CO poisoning. The article represents the consensus opinion of four recognized content experts in the field. Supporting data were drawn from the published, peer-reviewed literature on CO poisoning, placing emphasis on selecting studies that most closely mirror clinical practice.
A multifunctional CO/thermo/chemotherapy nanoplatform is here reported, which is composed of mesoporous carbon nanoparticles (MCN) as near infrared (NIR)-responsive drug carrier, doxorubicin (DOX) as ...chemotherapeutic drug and triiron dodecacarbonyl (FeCO) as thermosensitive CO prodrug. The nanoplatform could absorb near-infrared (NIR) light and convert it into ample heat to trigger CO release and could also release DOX in the acidic tumor microenvironment. More importantly, the generated CO molecules successfully increase cancer cell sensitivity to chemotherapeutics by the ferroptosis pathway. Subsequently, under the guidance of photoacoustic imaging, the FeCO-DOX@MCN nanoplatform demonstrates high treatment efficacies in vitro and in vivo by combination of chemotherapy, photothermal therapy and gas therapy. This multifunctional platform with excellent antitumor efficacy has great potential in precision cancer therapy.
Carbon monoxide (CO) is an intrinsic signaling molecule with importance on par with that of nitric oxide. During the past decade, pharmacologic studies have amply demonstrated the therapeutic ...potential of carbon monoxide. However, such studies were mostly based on CO inhalation and metal-based CO-releasing molecules. The field is now at the stage that a major effort is needed to develop pharmaceutically acceptable forms of CO for delivery via various routes such as oral, injection, infusion, or topical applications. This review examines the state of the art, discusses the existing hurdles to overcome, and proposes developmental strategies necessary to address remaining drug delivery issues.
This document provides an update to the European Respiratory Society (ERS)/American Thoracic Society (ATS) technical standards for single-breath carbon monoxide uptake in the lung that was last ...updated in 2005. Although both D
(diffusing capacity) and T
(transfer factor) are valid terms to describe the uptake of carbon monoxide in the lung, the term D
is used in this document. A joint taskforce appointed by the ERS and ATS reviewed the recent literature on the measurement of D
and surveyed the current technical capabilities of instrumentation being manufactured around the world. The recommendations in this document represent the consensus of the taskforce members in regard to the evidence available for various aspects of D
measurement. Furthermore, it reflects the expert opinion of the taskforce members on areas in which peer-reviewed evidence was either not available or was incomplete. The major changes in these technical standards relate to D
measurement with systems using rapidly responding gas analysers for carbon monoxide and the tracer gas, which are now the most common type of D
instrumentation being manufactured. Technical improvements and the increased capability afforded by these new systems permit enhanced measurement of D
and the opportunity to include other optional measures of lung function.
PDF
