Bromine inhalation mimics ischemia-reperfusion cardiomyocyte injury and calpain activation in rats

被引:20
作者
Ahmad, Shama [1 ]
Juncos, Juan Xavier Masjoan [1 ]
Ahmad, Aftab [1 ]
Zaky, Ahmed [1 ]
Wei, Chih-Chang [2 ,3 ]
Bradley, Wayne E. [2 ,3 ]
Zafar, Iram [1 ]
Powell, Pamela [2 ,3 ]
Mariappan, Nithya [1 ]
Vetal, Nilam [1 ]
Louch, William E. [4 ,5 ,6 ,7 ]
Ford, David A. [8 ,9 ]
Doran, Stephen F. [1 ]
Matalon, Sadis [1 ]
Dell'Italia, Louis J. [2 ,3 ]
机构
[1] Univ Alabama Birmingham, Dept Anesthesiol & Perioperat Med, 322 BMRII,901 19th St S, Birmingham, AL 35294 USA
[2] Univ Alabama Birmingham, Dept Med, Div Cardiovasc Dis, Birmingham, AL 35294 USA
[3] Dept Vet Affairs Med Ctr, Birmingham, AL USA
[4] Oslo Univ Hosp, Inst Expt Med Res, Oslo, Norway
[5] Univ Oslo, Oslo, Norway
[6] Univ Oslo, KG Jebsen Cardiac Res Ctr, Oslo, Norway
[7] Univ Oslo, Ctr Heart Failure Res, Oslo, Norway
[8] St Louis Univ, Dept Biochem & Mol Biol, St Louis, MO 63103 USA
[9] St Louis Univ, Ctr Cardiovasc Res, St Louis, MO 63103 USA
来源
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY | 2019年 / 316卷 / 01期
基金
美国国家卫生研究院;
关键词
calcium; calpains; cardiac; halogen; neutrophil; sarco(endo) plasmic reticulum Ca2+-ATPase; RETICULUM CA2+ ATPASE; INDUCED LUNG INJURY; MYOCARDIAL-ISCHEMIA; CHLORINATED LIPIDS; HEART; TARGET; MYELOPEROXIDASE; OVERLOAD; ALPHA; INFLAMMATION;
D O I
10.1152/ajpheart.00652.2017
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Halogens are widely used, highly toxic chemicals that pose a potential threat to humans because of their abundance. Halogens such as bromine (Br-2) cause severe pulmonary and systemic injuries; however, the mechanisms of their toxicity are largely unknown. Here, we demonstrated that Br-2 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. Br-2-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 Br-2 reactant-exposed rats. Increased bromination of sarco(endo) plasmic reticulum Ca2+-ATPase (SERCA) and increased phosphalamban after Br-2 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 (Br-2) 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 Br-2 exposure but also defines calpains as a potential target to treat Br-2-induced toxicity.
引用
收藏
页码:H212 / H223
页数:12
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