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Role of Chromogranin a in The Assessment of Sympathetic Activity in Acute Myocardial Infarction A THESIS SUBMITTED TO THE COUNCIL OF THE COLLEGE OF MEDICINE UNIVERSITY OF DUHOK IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF MASTER OF SCIENCE IN MEDICAL PHYSIOLOGY By Ihsan Husain Mohammed Ali B.V.M. College of Veterinary Medicine 2003 Supervised by Assistant Professor Assistant Professor Dr. Qasim H. Abdullah 1431 A.H. Dr. Sabri K. Shaikhow 2710 K. 2010 A.D. Abstract: Background Measurement of chromogranin A in plasma has been used for the diagnosis and prognosis of many endocrine and neuroendocrine tumors that are associated with increased catecholamines secretion (Marek, 2004). Little is known, however, about the magnitude of increased sympathetic activity after acute MI. Investigating the value of plasma chromogranin A as a quantitative measurement for this purpose probably will be of clinical significance. Objective: To evaluate the sympathetic nervous system activity, and related factors in patients with acute myocardial infarction by measuring plasma chromogrnin A. Subjects and Methods The study subjects included in this study were classified into two groups: patients with acute myocardial infarction (n = 45) and a group of apparently healthy subjects (n = 30). General information and history were completed, then measurement of vital signs, serum electrolytes, glomerular filtration rate (GFR), echocardiography parameters (ejection fraction and fractional shortening), plasma concentration of chromogranin A and serum concentrations of cardiac biomarkers (markers of myocardial injury) and uric acid were performed. In MI group, the samples were obtained within 24 hours of the onset of symptoms. Results A significant increase in the mean plasma chromogranin A level was observed in patients with acute myocardial infarction compared to the healthy subjects (182.6 Vs 307.4 ng/ml, respectively. P < 0.001). This was associated with significant increases in the serum levels of cardiac biomarkers (CK-MB and troponin I) and hs-CRP. Using receiver-operating characteristics (ROC) curve analysis, measurement of plasma chromogranin A level turned out to be a valid test for evaluation of sympathetic system activity with an area under the curve (AUC) of 0.817 (P < 0.001). The value of plasma chromogranin A level greater than or equal to 252.1ng/ml had an accuracy of 77.3 %, sensitivity of 64.4 % and 96.7 % specificity for establishing increased sympathetic system activity in patients with acute MI. In patients with acute MI, no significant correlation was observed between the plasma chromogranin A level and the time of sampling after the onset of symptoms (r = 0.056, P = 0.72). Moreover, patients with acute inferior wall MI showed no appreciable difference in plasma chromogranin A level from patients with other sites of myocardial wall infarction (308.1 Vs 306.8 ng/ml, respectively), associated with no significant difference in the vital signs between these two subgroups. Sympathetic system activity (represented by plasma chromogranin A level) was significantly lower in MI patients who received morphine compared to those with negative history of morphine administration (325.2 Vs 236 ng/ml, respectively with P = 0.01). However, plasma chromogranin A level was not influenced by gender, history of diabetes mellitus and smoking history. Conclusions: These data indicate that AMI is associated with increased sympathetic nervous system activity and measurement of plasma chromogranin A levels can be used readily to assess the extent of this activity. The magnitude of increased sympathetic system activity is not different in patients with acute inferior wall MI and patients with other sites of myocardial wall infarction. Morphine administration modulates sympathetic system activity after AMI.