Oxidative Stress in a Rodent Behavioral Model of Reversible Myocardial Dysfunction

Clinical reports suggest that emotional stress alone is sufficient to cause profound, but completely reversible myocardial dysfunction in patients. We previously reported that a combination of pre-natal and post-natal behavioral stresses results in myocardial dysfunction in a rodent model (Stress). Stress demonstrates both systolic (+dp/dt) and diastolic (−dp/dt) dysfunction by catheter-based hemodynamics, as well as, significantly attenuated hemodynamic and inotropic responses to the beta adrenergic agonist, isoproterenol in vivo and in vitro compared with matched controls (p<.05, for all). The p38 MAP kinase inhibitor, SB203580, both prevented and reversed the baseline reduction in +dp/dt and −dp/dt, as well as the blunted isoproterenol response in vivo and cardiac myocyte dysfunction in vitro (p<.05, for each). These physiologic defects are associated with decreased myocardial ATP and GSH/GSSG levels compared with matched controls (p<.05). We conclude that p38 MAP kinase activation in cardiac myocytes ...