Background: Trauma induces not only primary heart injury but also secondary heart injury.Our previous study has demonstrated that mechanical trauma could cause cardiomyocyte apoptosis which contributes to posttraumatic secondary cardiac dysfunction.The aim of the present study was to elaborate the potential mechanism involved in secondary post-traumatic cardiac dysfunction.Methods: Male adult rats were subjected to Noble-Collip drum with a total of 200 revolutions at a rate of 40 rpm.Then myocardial Caspase 3, 8, 9, 12activities, cardiac function in vitro, superoxide anion (O2-), total nitric oxide (NOx) content, nitrotyrosine (NT)content and nitric oxide synthase (NOS) expression in myocardial tissue were determined.Results: No direct mechanical traumatic injury was observed in the heart immediately after trauma.(1) Compared with the sham group, myocardial Caspase-3 activity in the traumatized rats significantly increased 6 h after trauma.And 12 h after trauma myocardial Caspase-3 activity reached the peak, which still remained at high level 24 h after trauma.(2) Administration of Z-VAD-FMK, a broad-spectrum caspase inhibitor, could reverse post-traumatic cardiac dysfunction evidenced by increased +dP/dtmax and decreased-dP/dtmax 24 h after trauma.(3) Compared with the sham group, myocardial Caspase-12 activity significantly increased 3h after trauma.6 h after trauma Caspase-12 activity reached the peak, but 12 h after trauma it decreased.Both myocardial Caspase-8 activity and Caspase-9activity markedly increased 24 h after trauma.(4) The myocardial O2-levels and NOx content obviously increased 6h after trauma, 12h after trauma it still remained at high level.The myocardial NT content, which reflected peroxynitrite (ONOO-) levels, increased 12 h after trauma.After FeTMPyP (ONOO- decomposition catalyst)treatment, the myocardial NT content and Caspase-3 activity significantly decreased.(5) iNOS expression in myocardial tissue significantly increased 6 h after trauma, and 12 h after trauma it reached its peak.While the myocardial eNOS expression at each time point in trauma group had no significant difference compared with trauma group.Administration of 1400W (a selective iNOS inhibitor) prevented the trauma-induced increase of the myocardial NOx, NT content and Caspase-3 activity.Conclusions: (1) Caspase-dependent apoptotic pathway played an important role in post-traumatic secondary cardiac dysfunction.(2) In the early period of trauma, cardiomyocyte apoptosis might be induced by activation the Caspase-12, an endoplasmic reticulum (ER)-specific caspase, following by activation of Caspase-8 (extrinsic pathway) and Caspase-9 (intrinsic pathway).(3)Mechanical trauma significantly increased the levels of O2, NO, ONOO and iNOS in myocardial tissues.The cleavage of ONOO and inhibition of iNOS significantly reduced cardiomyocyte apoptosis induced by mechanical trauma.