High Level of Serum Myoglobin in Human Intracerebral Hemorrhage: Implications for Large Hematoma Volume and Growth

 

Background

Myoglobin and cardiac troponin T are often elevated in patients with ischemic stroke. However, the association, if any, between both myoglobin and troponin T levels and hematoma volume in patients with intracerebral hemorrhage remains to be established. We investigate the possible relationship between admission myoglobin and troponin T levels and hematoma volume and growth.

Methods

A total of 143 patients with intracerebral hemorrhage admitted within 72 hours after symptom onset were divided into 4 groups according to the quartile of myoglobin levels. The information of hematoma was assessed with computed tomography scans. Serum myoglobin and cardiac troponin were tested at admission. The relationship between myoglobin levels and hematoma volume and growth was performed using univariate and multiple logistic regression and linear regression.

Results

High levels of serum myoglobin were associated with larger hematoma volume. In the highest quartile compared with the lowest quartile of myoglobin, the crude and adjusted odds ratios for the incidence of baseline hematoma volume greater than 30 mL were 2.14 (95% confidence interval 1.45-3.15) and 2.78 (95% confidence interval 1.57-5.00), respectively, in logistic regression. In linear regression, the adjusted B for the relationship of myoglobin and hematoma volume and the change of hematoma volume was .02 (95% confidence interval .01-.04, P = .007) and .021 (95% confidence interval .01-.03, P < .001), respectively, whereas high level of troponin T was not associated with large hematoma volume.

Conclusion

Our results first demonstrate that myoglobin is associated with larger hematoma volume and growth after adjusting potential confounding factors.

http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2016.02.005

 Ming Liu, MD, PhD, Stroke Clinical Research Unit, Department of Neurology, West China Hospital, Sichuan University, No. 37 Guo Xue Xiang, Chengdu, Sichuan Province 610041, China.

Prognostic implications of plasma myoglobin levels in patients with chronic kidney disease

Abstract


Purpose: Poor cardiovascular outcomes in chronic kidney disease (CKD) patients have prompted nephrologists to look for biomarkers that may improve risk stratification in this population.

The objective of this study was to evaluate plasma myoglobin (Mb) levels according to the CKD stage and to determine whether they are associated with overall, cardiovascular (CV) mortality, CV events, and renal outcomes. Methods: Plasma Mb levels were determined in 140 CKD patients at different stage (mean ± SD age: 67 ± 12; males: 61%) who were prospectively monitored for overall and CV mortality, CV events and CKD progression. Twenty-seven healthy subjects served as controls.

Results: Plasma Mb levels were higher in CKD patients than in controls and progressively increased as the glomerular filtration rate fell. Hemoglobin levels, CKD stage, the aortic calcification score and brain natriuretic peptide levels were associated with plasma Mb concentrations. In a multivariate analysis, only CKD stage was associated with Mb levels. During follow up (mean duration: 968 ± 374 days), 44 patients died and 63 had a cardiovascular event. In a crude analysis, plasma Mb >73.8 µg/l predicted overall and cardiovascular mortality and the occurrence of cardiovascular events (p = 0.01, 0.05 and 0.01, respectively). However, this association was lost after adjustment for other prognostic factors for mortality. Plasma Mb was not a significant predictor of the progression of CKD either.

Conclusions: Plasma Myoglobin levels were significantly higher in predialysis or dialyzed CKD patients than in healthy controls. However, we could not identify a relevant clinical outcome associated with this elevation. Larger studies are needed to confirm the present results

French National Institute of Health and Medical Research (INSERM), ERI-12 (EA 4292), Amiens - France and Clinical Research Center-Division of Clinical Pharmacology, Amiens University Hospital and the Jules Verne University of Picardie, Amiens - France Int J Artif Organs. 2012 Sep 6:0. doi: 10.5301/ijao.5000124.

Rapid diagnostic protocol for patients with chest pain

On the basis of thrombolysis in myocardial infarction (TIMI) score, ECG, and a point-of-care biomarker panel of troponin, creatine kinase MB, and myoglobin, Martin Than and colleagues(1) identified patients with chest pain who were at very low risk of a short-term major adverse cardiac event and who might be suitable for early discharge.
We are a little concerned about missing TIMI score data. The score includes “three or more risk factors for coronary artery disease” and “significant coronary stenosis at previous angiography” (yes=1, no=0). We wonder whether a patient without a regular health check was regarded by Than and colleagues as scoring 0 or 1? This could be an important issue considering the threshold considered (TIMI score ≥1=positive). We know, for instance, that people of low socioeconomic status have a lower access to health care, yet they have more risk factors for coronary heart disease.(2—4) Without a regular check-up, these people might have had a lower TIMI score than they should have.
In conclusion, we think that the accelerated diagnostic protocol should take into account the absence of medical follow-up to consider factors such as health inequalities.
We declare that we have no conflicts of interest.

References
1 Than M, Cullen L, Reid CM, et al. A 2-h diagnostic protocol to assess patients with chest pain symptoms in the Asia-Pacific region (ASPECT): a prospective observational validation study. Lancet 2011; 377: 1077-1084. Summary | Full Text | PDF(200KB) | CrossRef | PubMed
2 Kaplan GA, Keil JE. Socioeconomic factors and cardiovascular disease: a review of the literature. Circulation 1993; 88: 1973-1998. PubMed
3 Tyroler HA. The influence of socioeconomic factors on cardiovascular disease risk factor development. Prev Med 1999; 29: S36-S40. CrossRef | PubMed
4 Manrique-Garcia E, Sidorchuk A, Hallqvist J, Moradi T. Socioeconomic position and incidence of acute myocardial infarction: a meta-analysis. J Epidemiol Community Health 2011; 65: 301-309. PubMed

Serum Myoglobin

Serum myoglobin is a test that measures the amount of myoglobin in the blood.

Myoglobin is a protein in heart and skeletal muscles. When you exercise, your muscles use up any available oxygen. Myoglobin has oxygen attached to it, which provides extra oxygen for the muscle to maintain a high level of activity for a longer period of time.

When muscle is damaged, myoglobin is released into the bloodstream. Ultimately, it is removed in the urine.

Unmasking the Janus face of myoglobin in health and disease.

Abstract
For more than 100 years, myoglobin has been among the most extensively studied proteins. Since the first comprehensive review on myoglobin function as a dioxygen store by Millikan in 1939 and the discovery of its structure 50 years ago, multiple studies have extended our understanding of its occurrence, properties and functions. Beyond the two major roles, the storage and the facilitation of dioxygen diffusion, recent physiological studies have revealed that myoglobin acts as a potent scavenger of nitric oxide (NO(*)) representing a control system that preserves mitochondrial respiration. In addition, myoglobin may also protect the heart against reactive oxygen species (ROS), and, under hypoxic conditions, deoxygenated myoglobin is able to reduce nitrite to NO(*) leading to a downregulation of the cardiac energy status and to a decreased heart injury after reoxygenation. Thus, by controlling the NO(*) bioavailability via scavenging or formation, myoglobin serves as part of a sensitive dioxygen sensory system. In this review, the physiological relevance of these recent findings are delineated for pathological states where NO(*) and ROS bioavailability are known to be critical determinants for the outcome of the disease, e.g. ischemia/reperfusion injury. Detrimental and beneficial effects of the presence of myoglobin are discussed for various states of tissue oxygen tension within the heart and skeletal muscle. Furthermore, the impact of myoglobin on parasite infection, rhabdomyolysis, hindlimb and liver ischemia, angiogenesis and tumor growth are considered

Hendgen-Cotta UB, Flögel U, Kelm M, Rassaf T.

Department of Medicine, Division of Cardiology, Pulmonary Diseases and Angiology, University Hospital Düsseldorf, Düsseldorf, Germany.

mass spectrometric comparison of the interactions of cisplatin and transplatin with myoglobin

Abstract
Mass spectrometric studies of the interactions of cisplatin and transplatin with myoglobin (Mb) provide information concerning interaction kinetics, Mb adduct identity, and cisplatin and transplatin binding sites on Mb.

Although the Mb–cisplatin interaction is faster than the Mb–transplatin interaction, monoadducts and diadducts were formed in both the interactions over 30 h. In order to locate the binding sites of cisplatin and transplatin on Mb, digests of free Mb, Mb–cisplatin and Mb–transplatin adducts were subjected to analysis by Fourier transform mass spectrometry (FT-MS). This analysis revealed that two fragment ions, 1313.275+ and 1316.685+, were obtained only from the Mb–cisplatin and Mb–transplatin adduct digests.

Tandem mass spectrometry (MS/MS and MS3) of the 1313.275+ and 1316.685+ ions indicate that these ions arise from [Pt(NH3)]2+ and [Pt(NH3)2]2+, respectively, bound to peptide His97-Gly153. The product-ion spectra of the MS/MS and MS3 analyses of the 1313.275+ ion indicate a common binding site of cisplatin and transplatin on His116-His119 residues. The interactions of cisplatin and transplatin with a dipeptide His-Ser and the three dimensional (3D) structure of native Mb suggest that cisplatin and transplatin coordinate to His116 and His119.

Ting Zhaoa and Fred L. King, a,

a C. Eugene Bennett Department of Chemistry, West Virginia University, Morgantown, WV 26506-6045, USA

Expression and Functional Regulation of Myoglobin in Epithelial Cancers

(American Journal of Pathology. 2009;175:201-206.)

Myoglobin is a multifunctional heme protein that is thought to be expressed exclusively in myocytes. Its importance in both oxygen transport and free radical scavenging has been extensively characterized. We hypothesized that solid tumors could take advantage of proteins such as myoglobin to cope with hypoxic conditions and to control the metabolism of reactive oxygen and nitrogen species.

We therefore sought to establish whether myoglobin might be expressed and functionally regulated in epithelial tumors that are known to face hypoxia and oxidative stress during disease progression. We analyzed the expression of myoglobin in human epithelial cancers at both transcriptional and protein levels; moreover, we investigated the expression levels of myoglobin in cancer cell lines subjected to different conditions, including hypoxia, oxidative stress, and mitogenic stimuli. We provide evidence that human epithelial tumors, including breast, lung, ovary, and colon carcinomas, express high levels of myoglobin from the earliest stages of disease development.

In human cancer cells, myoglobin is induced by a variety of signals associated with tumor progression, including mitogenic stimuli, oxidative stress, and hypoxia. This study provides evidence that myoglobin, previously thought to be restricted to myocytes, is expressed at high levels by human carcinoma cells. We suggest that myoglobin expression is part of a cellular program aimed at coping with changed metabolic and environmental conditions associated with neoplastic growth.


Expression and Functional Regulation of Myoglobin in Epithelial Cancers
Simona Emilia Flonta*, Sabrina Arena*, Alberto Pisacane, Paolo Michieli and Alberto Bardelli* From the Laboratory of Molecular Genetics,* the Unit of Pathology, and the Division of Molecular Oncology, Institute for Cancer Research and Treatment, University of Turin Medical School, Turin; and the FIRC Institute of Molecular Oncology, Milan, Italy