Cocaine is known to produce life-threatening cardiovascular complications. When cocaine abuse is suspected, the investigation of the causes of death may be challenging in forensic medicine. No exhaustive answer can be obtained in most cases, reinforcing the need of further investigational tools to be used in this field. The increasing knowledge in the available biomarkers of cardiac function together with the availability of high sensitive assays can provide new tools in the investigation of sudden cardiac death in chronic abuser. In this work, the assessment of cardiac dysfunction was assessed by measuring troponin I and natriuretic peptides as biomarkers, and considering other standard endpoints used in preclinical toxicology studies. All the procedures and endpoints considered were designed to allow an easy and complete translation from the laboratory animals to human beings. Lister Hooded rats were treated with cocaine in chronic (up to 12-18 weeks) self administration studies. Troponin I (cTnI) and Atrial Natriuretic Peptide (ANP) were evaluated at different timepoints and heart weight and histopathology was assessed at the end of the treatment period. Furthermore, cocaine and its main metabolites were measured in the rat fur, to assess rats’ cocaine exposure. The results obtained showed that no morphological changes were present in the rat hearts, despite their chronic exposure to cocaine. Cardiac troponin I values in cocaine treated rats were normal, not different from control rats, further supporting the absence of morphological changes. On the contrary, ANP showed an increasing trend with time in all cocaine treated animals considered. The same approach was also adopted with a group of chronic health human cocaine abusers: 10 healthy cocaine abuser volunteers (with no cardiac pathologies) were considered, and troponin T, NT proBNP serum levels, cocaine and metabolites hair concentrations were measured. As in rats, no changes were observed in troponin serum levels, whereas the natriuretic peptides showed variations that suggest a parallelism with the minimal changes observed in rats. Similar changes are described in subjects considered at risk for hypertension. Natriuretic peptides are normally adopted as diagnostic/prognostic markers in the follow up of a number of cardiac or cardiovascular diseases; in this context, natriuretic peptides may represent a sensitive biomarker of heart dysfunction after cocaine chronic exposure.
|Titolo:||Natriuretic peptides elevations after chronic exposure to cocaine|
|Data di pubblicazione:||2012|
|Appare nelle tipologie:||07.13 Doctoral Thesis|
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|A Casartelli - Natriuretic peptides elevations after chronic exposure to cocaine.pdf||Tesi di Dottorato||Open Access Visualizza/Apri|