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

Halogens are widely used highly toxic chemicals that pose potential threat to humans due to their abundance. Halogens such bromine (Br2) cause severe pulmonary and systemic injuries however, the mechanisms of their toxicity are largely unknown. Here we demonstrate 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 (3-24h) increases in circulating troponin I, hFABP and NT-proBNP. Transmission electron microscopy demonstrated acute (3-24h) cardiac contraction band necrosis, disruption of z-discs, and mitochondrial swelling and disorganization.Echocardiography and hemodynamic analysis revealed left ventricular (LV) systolic and diastolic dysfunction at 7 days. Plasma and the 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 SERCA and increased phosphalamban after Br2 inhalation decreased cardiac SERCA activity by 70%. SERCA inactivation was accompanied by increased calcium sensitive LV calpain activity. A calpain specific inhibitor MDL28170 administered within 1h 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.