Abstract P061: The Possible Apoptosis Pathways Involved in Mechanical Trauma-Induced Secondary Heart Injury
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. The activities of cardiomyocyte Caspase 3, 8, 9, 12 were detected respectively by Fluorometric assays. The cardiac function in vitro was determined using a Langendorff isolated heart perfusion system.
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 6h after trauma (51±4 vs. 16±2, P<0.01). 12h after trauma myocardial Caspase-3 activity reached the peak (69±4 vs. Sham, P<0.01), which still remained at high level (46±3 vs. Sham, P<0.01) 24h after trauma. (2) Administration of Z-VAD-FMK, a broad-spectrum caspase inhibitor, could reverse post-traumatic cardiac dysfunction evidenced by increased +dP/dtmax [(4111±189) mmHg/sec, vs. sham (3414±208) mmHg/sec, P<0.01], and decreased -dP/dtmax [(-4997±351) mmHg/sec, vs. sham group (-3301±458) mmHg/sec, P<0.01] 24h after trauma. (3) Compared with the sham group, myocardial Caspase-12 activity significantly increased 3h after trauma (66±8 vs. 27±10, P<0.01). 6h after trauma Caspase-12 activity reached the peak (89±16, P<0.01 vs. Sham) , but 12h after trauma it decreased (P>0.05 vs. Sham). Both myocardial Caspase-8 activity and Caspase-9 activity markedly increased 24h after trauma (2312±648 vs. 1449±296, P<0.01 vs. Sham; 875±460 vs. 470±222, P<0.01 vs. Sham, respectively).
Conclusion: Caspase-dependent apoptotic pathway played an important role in post-traumatic secondary cardiac dysfunction. Moreover, in the early period of trauma, cardiomyocyte apoptosis was 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).
- © 2011 by American Heart Association, Inc.