title: Early markers for myocardial ischemia and sudden cardiac death.
abstract: The post-mortem diagnosis of acute myocardial ischemia remains a challenge for both clinical and forensic pathologists. We performed an experimental study (ligation of left anterior descending coronary artery in rats) in order to identify early markers of myocardial ischemia, to further apply to forensic and clinical pathology in cases of sudden cardiac death. Using immunohistochemistry, Western blots, and gene expression analyses, we investigated a number of markers, selected among those which are currently used in emergency departments to diagnose myocardial infarction and those which are under investigation in basic research and autopsy pathology studies on cardiovascular diseases. The study was performed on 44 adult male Lewis rats, assigned to three experimental groups: control, sham-operated, and operated. The durations of ischemia ranged between 5 min and 24 h. The investigated markers were troponins I and T, myoglobin, fibronectin, C5b-9, connexin 43 (dephosphorylated), JunB, cytochrome c, and TUNEL staining. The earliest expressions (≤30 min) were observed for connexin 43, JunB, and cytochrome c, followed by fibronectin (≤1 h), myoglobin (≤1 h), troponins I and T (≤1 h), TUNEL (≤1 h), and C5b-9 (≤2 h). By this investigation, we identified a panel of true early markers of myocardial ischemia and delineated their temporal evolution in expression by employing new technologies for gene expression analysis, in addition to traditional and routine methods (such as histology and immunohistochemistry). Moreover, for the first time in the autopsy pathology field, we identified, by immunohistochemistry, two very early markers of myocardial ischemia: dephosphorylated connexin 43 and JunB.
authors.affiliation: University Center of Legal Medicine Lausanne-Geneva, Rue Michel-Servet 1, CH 1211, Geneva, Switzerland. sara.sabatasso@hcuge.ch.|Institute of Anatomy, University of Bern, CH 3000, Bern, Switzerland. sara.sabatasso@hcuge.ch.
authors.forename: Sara
authors.initials: S
authors.lastname: Sabatasso
authors.affiliation: University Center of Legal Medicine Lausanne-Geneva, Rue Michel-Servet 1, CH 1211, Geneva, Switzerland.
authors.forename: Patrice
authors.initials: P
authors.lastname: Mangin
authors.affiliation: University Center of Legal Medicine Lausanne-Geneva, Rue Michel-Servet 1, CH 1211, Geneva, Switzerland.
authors.forename: Tony
authors.initials: T
authors.lastname: Fracasso
authors.affiliation: University Center of Legal Medicine Lausanne-Geneva, Rue Michel-Servet 1, CH 1211, Geneva, Switzerland.|Institute of Anatomy, University of Bern, CH 3000, Bern, Switzerland.
authors.forename: Milena
authors.initials: M
authors.lastname: Moretti
authors.affiliation: Genomics platform, Centre Médical Universitaire, University of Geneva, CH 1211, Geneva, Switzerland.
authors.forename: Mylène
authors.initials: M
authors.lastname: Docquier
authors.affiliation: Institute of Anatomy, University of Bern, CH 3000, Bern, Switzerland.
authors.forename: Valentin
authors.initials: V
authors.lastname: Djonov
mesh_terms: D000818:Animals; D000906:Antibodies / Q000032:analysis; D015415:Biomarkers / Q000032:analysis; D015938:Complement Membrane Attack Complex / Q000276:immunology; D018031:Connexin 43 / Q000276:immunology; D045304:Cytochromes c / Q000276:immunology; D016757:Death, Sudden, Cardiac; D005353:Fibronectins / Q000276:immunology; D049429:Forensic Pathology; D007150:Immunohistochemistry; D008297:Male; D023421:Models, Animal; D017202:Myocardial Ischemia / Q000175:diagnosis*; D009211:Myoglobin / Q000276:immunology; D011917:Rats, Inbred Lew; D014157:Transcription Factors / Q000276:immunology; D019210:Troponin I / Q000276:immunology; D020107:Troponin T / Q000276:immunology
chemical_list: D000906:Antibodies; D015415:Biomarkers; D015938:Complement Membrane Attack Complex; D018031:Connexin 43; D005353:Fibronectins; C584097:JunB protein, mouse; D009211:Myoglobin; D014157:Transcription Factors; D019210:Troponin I; D020107:Troponin T; D045304:Cytochromes c
keywords: Clinical pathology; Early markers; Forensic pathology; Myocardial ischemia; Sudden cardiac death