Immediate and Delayed Drug Therapy Effects on Low Dose Sarin Exposed Mice Myocardial Performance

Recent studies have shown that a single asymptomatic dose exposure to the nerve agent sarin can lead to long term cardiac dysfunction. This study looked at immediate and delayed treatment therapies post exposure on cardiac function. The mice were studied using electrocardiography (QTc, STc, and Tc intervals) and histological techniques (hematoxylin and eosin staining and brain natriuretic peptide (BNP) staining). Male C57BL/6J mice were injected with sarin (0.4LD50) and studied up to 11 weeks. Mice which were given a single dose of the nerve agent treatment atropine/2PAMCL, showed significantly higher cell size and BNP levels than the control (p = 0.001) and increased QTc and Tc intervals, all of which are indicators of cardiac insult . Mice which received drug treatments after the onset of cardiac remodeling showed increased (thus worsening) normalized heart size for isoproterenol (β agonist) treated mice (p = 0.0018) versus saline treated mice along with inverted T-waves pre cardiac stressing. Propranolol (β blocker) treated mice showed only T-wave depression and no difference in normalized heart size versus the saline group. These results suggest that standard treatment methods for nerve agent exposure are not effective in preventing long term cardiac dysfunction and in fact cause them