May 24 , 2002
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Neuroendocrinology Letters incl. Psychoneuroimmunology & Chronobiology

NEUROENDOCRINOLOGY LETTERS
including Psychoneuroimmunology, Neuro
psychopharmacology,
Reproductive Medicine, Chronobiology
and Human Ethology
ISSN 0172–780X

NEL Vol.23 No.2, April 2002

ORIGINAL ARTICLE
"Biomarkers for Myocardial Injury in Scorpion Sting"

2002; 23:133-140
pii: NEL220601A05
PMID:

full text pdf [604 kb]


Myocardial Injury in Scorpion Envenomed Children:
Significance of Assessment of Serum Troponin I and Interleukin-8

Abstract | Introduction | Materials and Methods:
Biochemical analysis; Statistical analysis | Results | Discussion
In conclusion | References


Abdel-Raheim A. M. Meki,1
Zeinab M. Mohey El-Deen, 2
Hassan M. Mohey El-Deen, 3

1. Biochemistry Department, Faculty of Medicine, Assuit University, Assiut, Egypt.
2. Pediatric Department, Faculty of Medicine, Assuit University, Assiut, Egypt.
3. Internal Medicine Department, Faculty of Medicine, Minia University, Minia, EGYPT.

Submitted: February 4, 2002
Accepted: February 13, 2002

Key words:
scorpion, children, cardiac injury, troponin I, interleukin-8.


Abstract

OBJECTIVES: (1) To investigate the significance of assessment of serum levels of cardiac troponin I (cTnI) and interleukin-8 (IL-8) beside other biomarkers of myocardial injury in scorpion envenomed children. (2) To find the correlation between these biochemical indices with clinical status, prognosis and outcome of these cases.

METHODS: Forty-one children in Upper Egypt were admitted to Pediatric Intensive Care Unit, Assiut University Hospital, for scorpion envenomation. They were compared with fifteen apparently healthy children of matching age as controls. The victims and controls were subjected to complete clinical examination, full blood count and arterial blood gases analysis. According to severity of scorpion envenomation, 17 children had manifestations of severe envenomation and clinical signs of toxic myocarditis (severe cases), 14 children had moderate manifestations of envenomation without clinical evidence of carditis (moderate cases) and 10 cases showing only mild symptoms of envenomation (mild cases). The serum levels of cTnI and IL-8 beside the enzymatic activities of creatine phosphokinase (CPK), CPK-MB isoenzyme (CPK-MB) and lactate dehydrogenase (LDH) were determined once for mild cases and controls on admission and twice for severe and moderate cases on admission and after 24 hrs. The measurements of electrocardiography (ECG), echocardiographic measurement of % fractional shortening of left ventricule (%SF), left ventricular ejection fraction (LVEF) and cardiac chambers dilatation were done for severe and moderate cases.

RESULTS: All the envenomed victims showed significantly higher mean values of CPK, CPK-MB, LDH, and IL-8 on admission in comparison to control group. cTnI was not detectable in the sera of control group as well as patients with mild envenomation. The mean values of CPK, CPK-MB, LDH, and IL-8 were significantly higher in severe cases while only IL-8 and CPK-MB were significantly higher in moderate cases in comparison with mild cases. The mean values of IL-8, cTnI, CPK, CPK-MB and LDH were significantly higher in severe cases both on admission and on follow-up comparing with moderate cases. The case fatality rate was 12.5% and all were from severe cases with toxic myocarditis (5/41=12.5%). The non-survivors victims showed significant higher mean values of only cTnI on admission and both cTnI and IL-8 on follow up in comparison to the survivors. Significant reduction of % SF and LVEF were noticed among the non-survivors in comparison to survivors. The cTnI showed 100% specificity and sensitivity for diagnosis of myocardial injury in relation to Echo finding in the envenomed victims. In severe cases, cTnI was positively correlated with IL-8 while negatively correlated with %SF and LVEF.

CONCLUSION: it may be suggested that cTnI is the most specific marker for diagnosis of myocardial injury in scorpion envenomation, which is almost associated with skeletal muscle injury. Other biochemical markers did not show such specificity. Also, IL-8 may be involved in the pathogenesis of myocardial injury of scorpion envenomation. Both cTnI and IL-8 may be useful to forecast the fatal outcome in scorpion envenomation.

Introduction

Scorpion envenomation is a common medical problem and life- threatening hazard in many countries. Scorpion envenomation in children can be a potentially fatal condition. Neurotoxins and cardiotoxins are present in the majority of scorpion venoms [1]. The signs and symptoms of envenomation are usually more severe in children especially younger ones [2-3]. Scorpion envenoming results in multi-organ system failure and death. It is brought about by a massive release of catecholamines, glucagon and angiotensin II and a simultaneous reduction in insulin levels [4-5]. The severity of envenomation is related to neurological and cardio-respiratory dysfunction. The mechanism of scorpion envenomation induced cardiac dysfunction is still unclear [6]. Gueron et al., [7] hypothesized that catecholamine storm post envenomation may cause cardiac dysfunction by catecholamine -induced hypoxia and that death might result from myocarditis and congestive heart failure [8]. Some authors suggested that cardiac dysfunction in scorpion envenomation may be due to a direct effect of scorpion venom evoking the so-called scorpionic myocarditis characterized by non-specific ultra-structural changes [9]. Nouira et al. [10] showed the presence of right and left ventricular dysfunction after scorpion envenomation providing further augmentation to the hypothesis of scorpionic myocarditis.
Myocardial damage in children may be clinically occult in a variety of stressful conditions. However, biochemical markers have not been routinely used in children at risk of myocardial damage due to lack of sufficient specificity. As the criterion for myocyte injury is not well established, so the need for a specific serum marker for myocardial injury might be useful to augment the clinical and echocardiographic (Echo) diagnosis of myocarditis [11]. Troponin I, C and T form a complex that regulates the Ca2+ mediated interaction of actin and myosin in striated muscles. Troponin I from the cardiac muscle and slow and fast twitch skeletal muscles are products of different genes with unique amino acid sequence. The developed monoclonal antibodies to cardiac troponin I (cTnI) have non cross reactivity with the skeletal muscle form were reported [12]. Briassoulis et al., [13] proved that cTnI is an early markers of viral myocarditis. Adams et al., [14] stated that the increases in cTnI don’t occur despite severe acute or chronic muscle injury even when level of creatine phosphokinase (CPK) and CPK-MB isoenzyme (CPK-MB) are increased unless cardiac injury is present.
Scorpion venoms can stimulate the neuroendocrinal-immunological axis by its ability to release catecholamines, corticosteroids, bradykinin and prostaglandins and all these agents proved to induce the release of immunological mediators as cytokines [15]. Cytokines regulate and amplify the immune response, induce tissue injury and mediate complications of the inflammatory response [16]. There is now accumulating evidence to suggest a causal relationship between overproduction of certain cytokines such as interleukin-1b (IL-1b) and interleukin-6 (IL-6) and both morbidity and mortality associated with critically ill patients [17]. Studies from Egypt indicated that levels of cytokines in scorpion envenomed children correlated with the clinical severity of envenomation [3].
Interleukin-8 (IL-8) is a potent chemoattractant factor for neutrophils, basophils and T lymphocytes and to control their trafficking [18]. Endothelial cells have been shown to produce IL-8 on stimulation with a variety of inflammatory mediators. Moreover, cultured endothelial cells release IL-8 under hypoxic conditions (Karakurum et al., 1994). According to the current knowledge, cytotoxic lymphocytes rather than monocytes are found at sites of myocardial inflammation. The inflammatory cytokines are target to myocardiac cells as the immune cells adhere to myocytes (Lang and Schreiner, 1994).
The aim of the present study was to assess the frequency of myocardial injury in scorpion envenomed children using the different biochemical markers (cTnI, IL-8, CPK, CPK-MB and LDH) hoping to identify the most specific marker for early detection of myocardial damage and forecasting the prognosis of these cases. In addition, to clarify the role of IL-8 in the pathogenesis of myocardial injury in scorpion envenomation and also to find the correlation between these biochemical indices with clinical status.

Materials and Methods
Biochemical analysis ... ....
Statistical analysis ... ....

Results
... ....

Discussion
... ....

In conclusion, the present study is considered the first study which provided evidence that: ... ....

 


REFERENCES

1 Frier-Maia L, Campos JA. Pathophysiology and treatment of scorpion poisoning. In Natural Toxins, Characterization, pharmacology and Therapeutics, eds CL. Ownby GV, Odell, 1989; pp. 130-159. Pergamon Press Oxford.
2 Muller GJ. Scorpionism in South Africa, a report of 42 serious scorpion envenomation. S Afr Med J 1993; 83:405-411.
3 Meki AR, Mohey EL-Dean ZM. Serum interleukin 1 beta, interleukin-6, nitric oxide and alpha antitrypsin in scorpion envenomed children. Toxicon 1998; 36:1851-1859.
4 Murthy RK, Hase NK. Scorpion envenoming and the role of insulin. Toxicon 1994; 32:1041-1044.
5 Mahadevan S. Scorpion Sting: Indian. Pediatr. 2000; 37: 504-514.
6 Abrough F, Nouira S, Boujdaria R. Cardiac dysfunction and pulmonary edema following scorpion envenomation [letter] Chest 1992; 102:1308-1309.
7 Gueron M, Adoleph R, Grup TL. Hemodynamic and myocardial consequences of scorpion venom. Am J Cardiol 1980; 45:979-986.
8 Gueron M, Illia R, Sofer S. The cardiovascular system after scorpion envenomation: a review. J Toxicol Clin Toxicol 1992; 30:245-258.
9 Trasiuk A, Sofer S, Huberfelo S. Hemodynamic effects following injection of venom from the scorpion Leirus quinquetriatus. J Crit Care 1994; 9:134-140.
10 Nouira S, Abroug F, Haguiga H. Right ventricular dysfunction following severe scorpion envenomation. Chest 1995; 108:682-687.
11 Smith SC, Allen PH. The role of T-cells in myosin-induced autoimmune myocarditis. Clin. Immunol. Immunopathol. 1993; 68:100-106.
12 Bodor GS, Porter S, Landt Y, Ladenson JH. Development of monoclonal antibodies for an assay of cardiac troponin I and preliminary results in suspected cases of myocardial infarction. Clin Chem 1992; 38:2203-2214.
13 Briassoulis G, Papodopolus N, Zavras V, Pailopoulos T, Hatzis V. Cardiac troponin I in fulminant adenovirus myocarditis treated with a 24 hour infusion of high-dose intravenous immunoglobulin. Pediatr Cardiol 2000; 21:391-394.
14 Adams JE, Bodor GS, Davila R, Delemz JA, Apple FS, Ladenson JH, Jaffe AS. Cardiac troponin I: A marker with specificity for cardiac injury. Circulation 1993; 88:101-106.
15 Chaudry IH, Stephan RN, Harkema JM, Dean RE. Immunological alterations following simple hemorrhage. In Immune consequences of Trauma, Shock and Sepsis, eds. F. Fasit, J. Ninnemann and D. Green, 1989; pp. 363-373. Springer-Verlag, Berlin.
16 Disaia PI, Greesman WT. Tumor immunology and other host defense mechanisms. In clinical Gynecology, 1989; P.594. Mosty, St. Louis, MI.
17 Roumen RMH, Hendriks T, Vander-Ven-Jongekrijg J. Cytokine patterns in patients after major vascular surgery, hemorrhagic shock, and severe blunt trauma: Relation with subsequent adult respiratory distress syndrome and multiple organ failure. Ann Surg 1993; 218:769-775.
18 Molad Y, Hanies KA, Anderson DC, Buyon JP, Cronstein BN. Immunocomplexes stimulate different signaling events to chemoattractants in the neutrophil and regulate L-selection and B2 integrin expression differently. Biochem J 1994; 299:881-887.
19 Karakurum M, Shreeniwas R, Chen J, Pinsky D, Yan SD, Anderson M, Sunouchi K, Major J, Hamilton T, Kuwabara K. Hypoxic induction of IL-8 gene expression in human endothelial cells. J Clin Invest 1994; 93:1564-1570.
20 Lang GL, Schreiner GF. Immune mechanisms of cardiac disease. N Engl J Med 1994; 330:1129-1135.
21 Hering SE; Jurca M, Vichi FL, Marisa M, Marques A, Cupo P. Reversible cardiomyopathy in patients with severe scorpion envenomation by Tityus serrulatus. Evaluation of enzymatic, electrocardiographic, echocardiographic alterations. Ann Trop Pediatr 1993; 13:173-182.
22 Murthy KRK, Billimora FR, Khopkar M, Dave KN. Acute hyperglycemia and hyperkalemia in acute myocarditis produced by scorpion (Buthus tamulus) venom injection in dogs. Indian Heart J 1986; 38:71-76.
23 Amitai Y. Clinical manifestations and management of scorpion envenomation. Public Health Rev 1998; 26:257-263.
24 Lipshultz SE, Rifai N, Sallan SE, Lipsitz SR, Dalton V, Sacks DB, Ottlinger ME. Predictive value of cardiac troponin T in pediatric patients at risk for myocardial injury. Circulation 1997; 96:2641-2648.
25 Sofer S, Shahak E, Solnim A, Gueron M. Myocardial injury without heart failure following envenomation by the scorpion L. quinquestriatus in children. Toxicol 1991; 3:383-385.
26 Larca LJ, Coppola JT, Honig S. Creatine kinase MB isoenzyme in dermatomyositis: a non-cardiac source. Ann Med 1981; 94:341-343.
27 Amaral CF, Lopes JA, Magalhaes RA, Rezende NA. Electrocardiographic, enzymatic and echocardiographic evidence of myocardial damage after Tityus serrulatus scorpion poisoning. Am J Cardiol 1991; 100:1057-1059.
28 Herrmann J, Volbra L, Haude M, Eggebrech H, Malyar N, Mann K, Erble R. Biochemical markers of ischemic and non-ischemic myocardial damage. Medizinische klinik 2001; 36:144-156.
29 Guest TM, Ramanathan AV, Peter G, Schechtman KB, Ladenson JH, Jaffe AS. Myocardial injury in critically ill patients. A frequency unrecognized complication. JAMA 1995; 273:1945-1949.
30 Das S, Nalini P, Anathakrishnan S, Sethuraman K, Balachander J, Srinivasan S. Cardiac involvement and scorpion envenomation in children. J Trop Pediatr 1995; 41:338-340.
31 Immer FF, Stocker FP, Seiler AM, Pfammatter JP, Printzen G, Carrel TP. Comparison of troponin I and troponin T after pediatric cardiovascular operation. Ann Thoracic Surg 1998; 66: 2073-2077.
32 Lavecchia L, Mezzena G, Zanolla L, Paaanaro M, Varotto L, Bonanno C, Ometto R. Cardiac troponin I as diagnostic and prognostic marker in severe heart failure. J Heart Lung Transplant 2000; 19:644-652.
33 Ammann P, Fehr T, Minder E, Gunter C, Bertel O. Elevation of cardiac troponin I in sepsis and septic shock. Int Care Med 2001; 27:965-969.
34 Lang K, Borner A, Figulla R. Comparison of biochemical markers for the detection of minimal myocardial injury: Superior sensitivity of cardiac troponin T ELISA. J Int Med 2000; 247:119-123.
35 Wan S, Yim AP. Cytokines in myocardial injury: Impact on myocardiac surgical approach. Eur J Cardiothorac Surg 1999; 16 (suppl.I): S 107-S 111.
36 Han RO, Ray PE, Baughman KL, Feldman AM. Detection of interleukin and interleukin-receptor mRNA in human heart by polymerase chain reaction. Biochem Biophys Res Commun 1991; 181:520-523.
37 Oz MC, Liao H, Naka Y, Smith CR, Rose EA, Stern DM, Pinsky DJ. Ischemia-induced interleukin-8 release after human heart transplantation. A potential role for endothelial cells. Circulation 1995; 92(9 Suppl):II 428-II 432.
38 Boyle Jr.EM, Kovacich JC, Hebert CA, Pohlman TH, Verier ED. Inhibition of interleukin-8 blocks myocardial ischemia-reperfusion injury. J Thorac Cardiovasc Surg 1998; 116:114-121.
39 Sofer S, Gueron M, White R, Lifshitz M, Apte R. Interleukin-6 release following scorpion sting in children. Toxicon 1996; 34:389-392.
40 Barbouche MR, Haguiga H, Nouira S, Krifi MN, Abroug F, Bouchoucha S, Dellagi K. Inflammatory cytokines and scorpionic envenomation. Analysis of serological levels in 46 Tunisian patients. Toxicon 1996; 34:156.
41 Magalhaes MM, Pereira ME, Amaral CF, Rez-Ende N, Campolina D, Bucaretchi F. Serum levels of cytokine in patients envenomed by Tityus serrulatus Scorpion sting. Toxicon 1999; 37:1155-1164.
42 Endo S, Inada K, Kadae HA, Rakakawa N, Takauwa T, Yamada Y, Yoshida M. Nitrite/ nitrate oxide (NOX) and cytokine levels in patients with septic shock. Res Commun Molec Pathol Pharmac 1996; 91:347-356.
43 Yasunori A, Masanobu K, Masatoshi K. Transient rise in serum interleukin-8 concentration during acute myocardial infarction. Br Heart J 1993; 70:132-134.
44 Ismail M. The scorpion envenoming syndrome. Toxicon 1995; 33:825-828.
45 Biswal N, Charan MV, Betsy M, Mahadevan S. Management of scorpion envenomation. Pediatrics Today 1999; 2:420-426.
46 Hirsch R, Landt Y, Porters S, Canter CE, Jaffe AS, Ladenson JH, Grant JW, Landt M. Cardiac troponin I in pediatrics: Normal values and potential use in the assessment of cardiac injury. J Pediatr 1997; 130:872-877.

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