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      Micromorphological changes in cardiac tissue of drug-related deaths with emphasis on chronic illicit opioid abuse

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          Abstract

          Aims

          The main intention of this retrospective study was to investigate whether chronic illicit drug abuse, especially the intravenous use of opioids (heroin), could potentially trigger the development of myocardial fibrosis in drug addicts.

          Design

          A retrospective case–control study was performed using myocardial tissue samples from both drug-related deaths (DRD) with verifiable opioid abuse and non-drug-related deaths in the same age group.

          Setting

          Department of Forensic Medicine, Medical University of Vienna, Austria (1993–94).

          Participants

          Myocardial specimens were retrieved from 76 deceased intravenous opioid users and compared to those of 23 deceased non-drug users.

          Measurements

          Drug quantification was carried out using the enzyme-multiplied immunoassay technique (EMIT), followed by [gas chromatography–mass spectrometry (GC–MS), MAT 112®], and analysed using the Integrator 3390A by Hewlett Packard® and LABCOM.1 computer (MSS-G.G.). The amount of fibrous connective tissue (FCT) in the myocardium was determined by using the morphometric software LUCIA Net version 1.16.2 ©, Laboratory Imaging, with NIS Elements 3.0®.

          Findings

          Drug analysis revealed that 67.11% were polydrug users and the same proportion was classified as heroin addicts (6-monoacetylmorphine, 6-MAM)—32.89% were users of pure heroin. In 76.32% of DRD cases, codeine was detected. Only 2.63% consumed cocaine. The mean morphine concentrations were 389.03 ng/g in the cerebellum and 275.52 ng/g in the medulla oblongata, respectively. Morphometric analysis exhibited a strong correlation between DRD and myocardial fibrosis. The mean proportion of FCT content in the drug group was 7.6 ± 2.9% (females: 6.30 ± 2.19%; males: 7.91 ± 3.01%) in contrast to 5.2 ± 1.7% (females: 4.45 ± 1.23%; males: 5.50 ± 1.78%) in the control group, indicating a significant difference ( P = 0.0012), and a significant difference in the amount of FCT between females and males ( P = 0.0383). There was no significant interaction of age and FCT ( P = 0.8472).

          Conclusions

          There is a long-term risk of cardiac dysfunction following chronic illicit drug abuse with opioids as a principal component. Regular cardiological examination of patients receiving substitution treatment with morphine is strongly recommended.

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          Most cited references41

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          The Pharmacological Basis of Therapeutics

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            Gene expression in fibroblasts and fibrosis: involvement in cardiac hypertrophy.

            Structural remodeling of the ventricular wall is a key determinant of clinical outcome in heart disease. Such remodeling involves the production and destruction of extracellular matrix proteins, cell proliferation and migration, and apoptotic and necrotic cell death. Cardiac fibroblasts are crucially involved in these processes, producing growth factors and cytokines that act as autocrine and paracrine factors, as well as extracellular matrix proteins and proteinases. Recent studies have shown that the interactions between cardiac fibroblasts and cardiomyocytes are essential for the progression of cardiac remodeling. This review addresses the functional role played by cardiac fibroblasts and the molecular mechanisms that govern their activity during cardiac hypertrophy and remodeling. A particular focus is the recent progress toward our understanding of the transcriptional regulatory mechanisms involved.
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              Infarct scar: a dynamic tissue.

              Y. Sun (2000)
              Infarct scar, a requisite to the rebuilding of necrotic myocardium following myocardial infarction (MI), has long been considered inert. Earlier morphologic studies suggested healing at the infarct site was complete within 6-8 weeks following MI and resultant scar tissue, albeit necessary, was acellular and simply fibrillar collagen. Utilizing molecular and cellular biologic technologies, recent studies indicate otherwise. Infarct scar is composed of phenotypically transformed fibroblast-like cells, termed myofibroblasts (myoFb) because they express alpha-smooth muscle actin (alpha-SMA) and these microfilaments confer contractile behavior in response to various peptides and amines. These cells are nourished by a neovasculature and are persistent at the MI site, where they are metabolically active expressing components requisite to angiotensin (Ang) peptide generation, including converting enzyme, receptors for AngII and transforming growth factor (TGF)-beta1. They continue to elaborate fibrillar type I collagen. Their generation of these peptides contribute to ongoing scar tissue collagen turnover and to fibrous tissue formation of noninfarcted myocardium. Infarct scar contraction accounts for its thinning and its tonus may contribute to abnormal ventricular chamber stiffness with diastolic dysfunction. Infarct scar is a dynamic tissue: cellular, vascularized, metabolically active and contractile. Pharmacologic interventions with angiotensin converting enzyme inhibitor or AT1 receptor antagonist has proven effective in attenuating scar tissue metabolic activity and minimizing adverse accumulation of fibrous tissue in noninfarcted myocardium.
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                Author and article information

                Journal
                Addiction
                Addiction
                add
                Addiction (Abingdon, England)
                Blackwell Publishing Ltd
                0965-2140
                1360-0443
                July 2013
                12 April 2013
                : 108
                : 7
                : 1287-1295
                Affiliations
                Department of Forensic Medicine, Medical University Vienna Vienna, Austria
                Author notes
                Correspondence to: Daniele U. Risser, Department of Forensic Medicine, Medical University of Vienna, Sensengasse 2, A-1090 Vienna, Austria. E-mail: daniele.risser@ 123456meduniwien.ac.at
                Article
                10.1111/add.12106
                3746107
                23297783
                af346060-3229-446a-a296-019f2e7f1021
                © 2013 Society for the Study of Addiction

                Re-use of this article is permitted in accordance with the Creative Commons Deed, Attribution 2.5, which does not permit commercial exploitation.

                History
                : 12 January 2012
                : 13 March 2012
                : 21 December 2012
                Categories
                Research Reports

                Clinical Psychology & Psychiatry
                drug-related deaths,heroin addiction,micromorphological changes,myocard fibrosis,opiates,opioids

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