Can reduced glutathione protect the myocardium in patients with carbon monoxide poisoning?

 Acute carbon monoxide poisoning (ACMP), commonly known as gas poisoning, is the main cause of acute poisoning deaths, in China, the incidence of ACMP and the death rate of all kinds of acute poisoning of the first [1] O ACMP refers to a certain amount of inhalation of carbon monoxide at a certain time of acute hypoxic disease caused by cerebral hypoxia is the most prominent symptom O Clinical patients with ACMP often focus on the recovery of neurological dysfunction caused by cerebral hypoxia, often ignoring the damage to the myocardium O Recent studies [2] found that moderate and severe ACMP patients are often combined with significant myocardial damage O And cardiac damage is often hidden Clinical attention to ACMP patients is often focused on the recovery of neurological dysfunction caused by brain tissue hypoxia, often ignoring the damage to the myocardium O Recent studies [2] found that patients with moderate and severe ACMP often combined with obvious myocardial damage O While the cardiac damage is often masked, heart failure and severe cardiac arrhythmia often occur, which can lead to deterioration of the patient's condition and death of the crusher O Therefore, for patients with ACMP, protection of the myocardial function is an important link in the treatment of ACMP O From January 2003 to December 2009, the authors used the following methods to evaluate the effectiveness of the treatment of ACMP patients. From January 2003 to December 2009, the author used reduced glutathione (GSH) to treat myocardial damage caused by ACMP, and observed the changes of creatine kinase isoenzyme (CK-MB) and troponin I (cTnI) before and after the treatment, which are reported as follows.

 

1 Objects and Methods

1.1 Subject of the study    

Ninety-three patients with acute moderate or severe ACMP who were admitted to our hospital from January 2003 to December 2009, all of them had a clear history of ACMP and positive COHb qualitative test (using the boiling method and healthy human venous blood as the control) O were randomly divided into 52 cases in the treatment group and 41 cases in the control group: male in the treatment group, male in the control group, male in the treatment group, male in the control group, male in the control group, male in the treatment group, male in the control group, male in the treatment group, male in the control group.

In the control group, there were 20 males and 21 females with a median age of 35.43 (18-79) years. O Degree of poisoning: 38 moderate and 14 severe cases in the treatment group, 25 and 16 cases in the control group respectively. O Excluding those who died during treatment and those who had suffered from cardiomyositis, cardiac failure, shock, serious arrhythmia and other recent history of poisoning. O Screening criteria: no cardiac, hepatic, renal or thyroid diseases before poisoning, diagnosis and grading were established according to the "Diagnostic standards for occupational acute carbon monoxide poisoning (GBZ23-2002)" of the Ministry of Health. O Differences between the two groups in terms of gender, age, and severity were not statistically significant (p<0.05).

 

1.2 Treatment   

Both groups were treated with conventional therapy: (1) high-flow oxygen inhalation by normal-pressure nasal cannula; (2) hyperbaric oxygen therapy; (3) dehydration and cranial pressure reduction therapy; (4) energy synthesis therapy; (5) prevention of infections and symptomatic treatment O In the treatment group, on the basis of the conventional treatment, GSH was added 1,800 mg/times per day, intravenously once a day, and the course of treatment was 7 d. The treatment group was treated with GSH for 7 days.

 

1.3 Measurement indicators    

CTnI was measured by ELISA (BeCkman, Germany), and serum CTnI ≥0.40 μg/L was considered as myocardial injury. CK-MB was measured by enzyme rate method (Olympus Vistro 250, Japan), and the reference range of normal CK-MB value was ≤25 U/L. All patients were admitted to the hospital and at the end of treatment. All patients had 3 mL of venous blood collected at the time of admission and at the end of the treatment, and CTnI and CK-MB were measured separately after serum separation.

1.4 Statistical processing SPSS13.0 statistical software was used to complete the data analysis, the measurement data were expressed by x ± s, t-test was performed, and the rate of comparison was performed by the "2-test," and the difference of P < 0.05 was regarded as statistically significant.

 

2 Results

There was no statistically significant difference in serum CTnI levels between the two groups before treatment (P > 0.05), and there was a statistically significant difference in serum CTnI levels between the two groups before and after treatment (both P < 0.01). At the end of the treatment course, serum CTnI levels of the treatment group were significantly lower than those of the control group, and the difference was statistically significant (P < 0.05), as shown in Table 1.

There was no statistically significant difference between the serum CK-MB levels of the two groups before treatment (P > 0.05), and the difference between the serum CK-MB levels of the two groups before and after treatment was statistically significant (both P < 0.01). At the end of the treatment course, the serum CK-MB levels of the treatment group were significantly lower than those of the control group, and the difference was statistically significant (P < 0.05), as shown in Table 2.

 

3 Discussion

ACMP is one of the most common life and occupational poisoning, has become an important cause of morbidity and mortality Carbon monoxide inhalation, 85% and the blood of red blood cells hemoglobin binding, the formation of stable COHb, impede the hemoglobin oxygen and oxygen release, the body of all tissues can be a certain degree of damage, but because of the brain tissue is the most sensitive to oxygen deprivation, it is the first to be damaged The presence of COHb in the blood makes the brain, heart and other systems of vascular endothelial cells to reduce energy synthesis, impaired cell metabolism, resulting in intracellular acidosis, increased permeability of cell membranes, endothelin and other vasoconstrictors released into the blood. The presence of COHb in the blood reduces the energy synthesis of vascular endothelial cells of brain, heart and other systems, impaired cell metabolism, resulting in intracellular acidosis, increased permeability of cell membranes, increased release of vasoconstrictive substances such as endothelin into the bloodstream, which in turn causes structural damage to cardiac myocytes. In addition, disorders of neurofluidic regulation manifested by increased levels of catecholamines and epinephrine, which further cause coronary artery spasm and constriction, elevation of blood pressure, accelerated heart rate, resulting in myocardial ischemia, and the heart rate increased. The incidence of myocardial damage caused by ACMP was reported to be 13.58%~32.00%, and the incidence and severity of myocardial damage increased significantly with the aggravation of toxicity. In addition, patients with myocardial damage had no obvious subjective symptoms, or they were covered up by the symptoms of central nervous system damage, which were often neglected and delayed in treatment. In addition, most patients with myocardial damage do not have obvious subjective symptoms, or are masked by symptoms of central nervous system damage, which are often neglected by the clinic and delayed diagnosis.

 

GSH participates in triple completion acid cycle, promotes bile acid metabolism, and can activate a variety of enzymes, thus promoting sugar, fat and protein metabolism GSH can bind with free radicals in the body through Ryukyl radicals to accelerate the excretion of free radicals, and can reduce tissue damage and promote the repair of patients suffering from systemic or localized hypoxemia caused by intoxication. Through the reaction of transmethylation and trans-propylation of amino acids, GSH also protects the synthesis of the liver, and detoxification, CK-MB and troponin I/T (CTnI/T) are specific and sensitive markers for myocardial injury. CTnI/T is the most sensitive and specific serum biochemical marker for myocardial injury. CTnI and CTnT have the same sensitivity, but the specificity of CTnI is higher than that of CTnT, so CTnI is the most sensitive and specific marker for myocardial injury. Therefore, CTnI is the most sensitive and specific as an indicator of myocardial damage.

 

In the course of ACMP treatment, after normobaric and hyperbaric oxygen therapy, with the improvement of microcirculation and the recovery of tissue oxygenation, there is hypoxia/reoxygenation (A/R) injury in the tissue, which may cause permanent damage to the myocardium if no active and effective measures are taken. GSH can reduce the A/R injury of cardiomyocytes by inhibiting the expression of inflammatory factors and other pathways. The main mechanism of A/R injury is calcium overload, The main mechanisms of A/R injury are calcium overload, oxygen radicals, and leukocyte aggregation, etc. However, GSH can inhibit the release of calcium ions by binding to the luciferase site of the small molecule chloride channel protein, leading to structural changes in the protein, and inhibiting the opening of the channel. When [Ca2+] rises to a certain concentration, the Ca2+-Mg2+-ATPase enzyme is activated, hydrolyzes the ATP to provide energy, and pumps the Ca2+ out of the cell or uptake it from the endoplasmic reticulum and mitochondria, thus reducing the cytosolic Ca2+ concentration. At the same time, GSH can directly eliminate oxygen radicals, hydrogen peroxide and hydroxyl radicals, and can also react with myeloperoxidase-derived oxidants produced by leukocytes during oxidative stress, such as hypochlorous acid and chloramine, preventing them from participating in the oxygen radical generation reaction; and GSH can also inhibit the activities of NADPH and cytochrome P450 reductase to reduce the free radicals produced by the NADPH oxidase system. oxidase system, thus reducing the cytotoxicity of this system in A/R injury.[4] Hu Tao et al.[5] used high dose of vitamin C, and Xiao Li et al.[6] used edaravone oxygen radical scavenger in the treatment of ACMP with good results.

 

In this study, the levels of CTnI and CK-MB were significantly lower in the treatment and control groups before and after treatment, indicating that myocardial damage in patients with moderate-to-severe ACMP is easy to occur. The levels of cTnI and CK-MB in the treatment group with the addition of GSH were significantly lower than those in the control group (P < 0.05), indicating that GSH has a certain auxiliary therapeutic effect on the elevation of cTnI and CK-MB in the patients with ACMP 9. In summary, GSH has a protective effect on cardiomyocytes of ACMP patients, and in clinical practice, cardiac damage caused by ACMP 9 should be emphasized and early intervention is recommended.

 

References.

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[2] Henry C R , Satran D , Lindgren B , et al. Myocardial injury and long term mortality following moderate to severe carbon monoxide poisoning [J]. jama , 2006 ,295(4) :398-402.

[3] ZHANG Jianguo,ZHANG Huiru,SHI Xueying,et al. Dynamic changes of serum enzyme activity in patients with acute carbon monoxide poisoning [J].  Chinese Journal of Labor Health and Occupational Diseases , 2003 ,21 (1) :51-53.

[4] Scholz R W , Reddy P V , Wynn M K , et al. Glutathione dependent factors and inhibition of rat liver microsomal lipid peroxidation [J].  Free Radic Biol Med , 1997 ,23 (5) :815 - 828.

[5] HU Tao ,YIN Wen ,LI Xiaoyi ,et al. Protective effect of high-dose vitamin C on myocardium of patients with acute carbon monoxide poisoning [J].   China Emergency Medicine , 2009 ,29(7): 637-639.

[6] XIAO Li,WANG Dajun. Therapeutic effect of ganglioside and edaravone combined with hyperbaric oxygen in the treatment of acute carbon monoxide poisoning [J]. Shandong Medicine , 2010 ,50(31): 102-103.