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Cocaine-associated increase of atrial natriuretic peptides: an early predictor of cardiac complications in cocaine users?
  1. Alessandro Casartelli1,2,
  2. Lisa Dacome1,
  3. Michela Tessari1,
  4. Jennifer Pascali2,
  5. Federica Bortolotti2,
  6. Maria Teresa Trevisan4,
  7. Oliviero Bosco5,
  8. Patrizia Cristofori3,
  9. Franco Tagliaro2
  1. 1Toxicology and Pathology Department, Aptuit Medicine Research centre, Verona, Italy
  2. 2Faculty of Medicine and Surgery, Public Health and Community Medicine Department, University of Verona, Verona, Italy
  3. 3GlaxoSmithKline Pathology-Safety Assessment, Ware Herfordshire, UK
  4. 4Analysis Laboratory, Fracastoro Hospital, Verona, Italy
  5. 5Servizio Tossicodipendenze (SERT), Verona, Italy
  1. Correspondence to Dr Alessandro Casartelli, Toxicology and Pathology Department, Aptuit Medicine Research centre, via Fleming 4, Verona 37135, Italy; alessandro.casartelli{at}aptuit.com

Abstract

Objective Cocaine is known to produce life-threatening cardiovascular complications, and the investigation of the causes of death may be challenging in forensic medicine. The increasing knowledge of the cardiac function biomarkers and the increasing sensitivity of assays provide new tools in monitoring the cardiac life-threatening pathological conditions and in the sudden death investigation in chronic abusers. In this work, cardiac dysfunction was assessed in an animal model by measuring troponin I and natriuretic peptides as biomarkers, and considering other standard endpoints used in preclinical toxicology studies.

Methods Lister Hooded rats were treated with cocaine in chronic self-administration studies. Troponin I (cTnI) and atrial natriuretic peptide (ANP) were evaluated at different time points and heart weight and histopathology were 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. All the procedures and endpoints considered were designed to allow an easy and complete translation from the laboratory animals to human beings, and the same approach was also adopted with a group of 10 healthy cocaine abuse volunteers with no cardiac pathologies.

Results Cardiac troponin I values were unaffected, and ANP showed an increasing trend with time in all cocaine-treated animals considered. Similarly, in the healthy volunteers, no changes were observed in troponin serum levels, whereas the N-terminal brain natriuretic pro-peptide (NT proBNP) showed variations comparable with the changes observed in rats.

Conclusions In conclusion, natriuretic peptides could represent an early indicator of heart dysfunction liability in chronic cocaine abusers.

  • Heart Failure

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