engleski

Cardiomyocytes calpain 2 expression: Diagnostic forensic marker for sudden cardiac death caused by early myocardial ischemia and an indicator of the duration of myocardial agonal period?

Sudden cardiac death (SCD) is an unexpected natural death of cardiac etiology and occurs within one hour of the onset of cardiac symptoms in an apparently healthy subject or within 24 h if death is not witnessed. The diagnosis of early myocardial ischemia (EMI) or acute myocardial infarction (AMI) after death is a challenge for forensic pathologists especially when death occurs in a short period of time after the onset of myocardial ischemia. Disorder of cardiomyocytes Ca2+ homeostasis caused by myocardial ischemia during SCD can lead to the activation of calcium-activated non-lysosomal cysteine protease, including calpains. They serve as a proteolytic unit for cell balance and also participate in the processes of apoptosis and necrosis. Agony is a period that precedes somatic death that differs from cellular agony which may evolve for hours after somatic death lasting differently depending on the cell type and mechanism of death. We hypothesize that the expression of calpain 2 in cardiomyocytes could be a specific and sensitive diagnostic forensic marker for SCD caused by EMI and an indicator of the duration of myocardial agonal period. We will conduct a retrospective study that will prove this hypothesis on the respondents who died of SCD by EMI and AMI, instant death by head gunshot and hanging. There is no data on such an analysis in the available literature. The standard hematoxylin-eosin staining will be used to detect cardiac tissue damage. The expression of calpain 2 in cardiomyocytes will be analyzed immunohistochemically. In SCD caused by EMI we expect lower level of calpain 2 expressionin comparison to AMI due to shorter duration of dying. Similar, we predict in the remote region lower calpain 2 expression than in the region of ischemia for both EMI and AMI. In instant death caused by perforating traumatic brain injury we expect mild or no calpain 2 expression throughout the whole myocardium because of very short (immediate) duration of dying. In death caused by hanging calpain 2 expression throughout the whole myocardium should be strong because of longer cellular agonal period. We expect that our results would indicate the immediate activation of calpain 2 in different causes of cardiomyocytes death. From the degree of expression of calpain 2 we could conclude about the duration of cardiomyocytes agony so calpain 2 could be used as a marker for the assessment the duration of somatic and cellular agony.

Calpain ; Sudden cardiac death ; Early myocardial ischemia ; Acute myocardial infarction ; Forensic pathology ; Immunohistochemistry

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