Bromine inhalation mimics ischemia-reperfusion cardiomyocyte injury and calpain activation in rats
| Autor: | Nilam Vetal, Shama Ahmad, Nithya Mariappan, Pamela C. Powell, Stephen F. Doran, Aftab Ahmad, David A. Ford, Juan Xavier Masjoan Juncos, Wayne E. Bradley, Iram Zafar, Chih-Chang Wei, Sadis Matalon, William E. Louch, Ahmed Zaky, Louis J. Dell’Italia |
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| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine Physiology Diastole Ischemia chemistry.chemical_element Myocardial Reperfusion Injury 030204 cardiovascular system & hematology Pharmacology Calcium Mitochondria Heart Sarcoplasmic Reticulum Calcium-Transporting ATPases Rats Sprague-Dawley 03 medical and health sciences 0302 clinical medicine Physiology (medical) Administration Inhalation Ventricular Dysfunction medicine Animals Myocytes Cardiac Cells Cultured Ventricular Remodeling biology Inhalation Calpain Chemistry Hemodynamics Bromine medicine.disease Myocardial Contraction Rats 030104 developmental biology cardiovascular system biology.protein Cardiology and Cardiovascular Medicine Biomarkers Research Article |
| Zdroj: | American Journal of Physiology-Heart and Circulatory Physiology. 316:H212-H223 |
| ISSN: | 1522-1539 0363-6135 |
| DOI: | 10.1152/ajpheart.00652.2017 |
| Popis: | Halogens are widely used, highly toxic chemicals that pose a potential threat to humans because of their abundance. Halogens such as bromine (Br2) cause severe pulmonary and systemic injuries; however, the mechanisms of their toxicity are largely unknown. Here, we demonstrated that Br2 and reactive brominated species produced in the lung and released in blood reach the heart and cause acute cardiac ultrastructural damage and dysfunction in rats. Br2-induced cardiac damage was demonstrated by acute (3–24 h) increases in circulating troponin I, heart-type fatty acid-binding protein, and NH2-terminal pro-brain natriuretic peptide. Transmission electron microscopy demonstrated acute (3–24 h) cardiac contraction band necrosis, disruption of z-disks, and mitochondrial swelling and disorganization. Echocardiography and hemodynamic analysis revealed left ventricular (LV) systolic and diastolic dysfunction at 7 days. Plasma and LV tissue had increased levels of brominated fatty acids. 2-Bromohexadecanal (Br-HDA) injected into the LV cavity of a normal rat caused acute LV enlargement with extensive disruption of the sarcomeric architecture and mitochondrial damage. There was extensive infiltration of neutrophils and increased myeloperoxidase levels in the hearts of Br2- or Br2 reactant-exposed rats. Increased bromination of sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) and increased phosphalamban after Br2 inhalation decreased cardiac SERCA activity by 70%. SERCA inactivation was accompanied by increased Ca2+-sensitive LV calpain activity. The calpain-specific inhibitor MDL28170 administered within 1 h after exposure significantly decreased calpain activity and acute mortality. Bromine inhalation and formation of reactive brominated species caused acute cardiac injury and myocardial damage that can lead to heart failure. NEW & NOTEWORTHY The present study defines left ventricular systolic and diastolic dysfunction due to cardiac injury after bromine (Br2) inhalation. A calpain-dependent mechanism was identified as a potential mediator of cardiac ultrastructure damage. This study not only highlights the importance of monitoring acute cardiac symptoms in victims of Br2 exposure but also defines calpains as a potential target to treat Br2-induced toxicity. |
| Databáze: | OpenAIRE |
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