Apoptosis in cardiac myocytes during the early stage after severe burn.
BACKGROUND
Cardiac dysfunction after severe burn is associated with postburn myocardial injury. We hypothesize that myocyte apoptosis is triggered and presented as the pathologic basis of postburn myocardial injury during the early stage after severe burn, and that apoptosis may be related to inflammatory responses in the postburn myocardium.


METHODS
Rats with 40% total body surface area full-thickness burn were used. The following functions were measured at several time points after the burn injury: myocyte apoptosis (TUNEL staining, DNA ladder, and caspase-3 activity assay); mRNA levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (reverse transcriptase-polymerase chain reaction [RT-PCR]); activities of myeloperoxidase and p38 mitogen activated protein (MAP) kinase (Western blots); and left cardiac function.


RESULTS
TUNEL positive myocytes appeared as early as 6-hour and their numbers showed further increases at 12-hour and 24-hour postburn; DNA fragmentation was clearly observed, and caspase-3 activity was significantly increased in the myocardium after burn. Infiltration of neutrophils, evidenced by the levels of myeloperoxidase activity, expression of TNF-alpha, and p38 MAP kinase activity in the heart, were all significantly increased within 24-hour after burn. Cardiac function was decreased after burn, which approximately paralleled the increased amount of cardiac apoptosis.


CONCLUSIONS
These results demonstrate that cardiomyocyte apoptosis progressively develops during the early stage after severe burn, which may in part contribute to burn-induced cardiac dysfunction. Myocardial inflammatory responses, evidenced by the increased infiltration of neutrophils, as well as production of TNF-alpha probably because of the activation of p38 MAP kinase, may be involved in burn-induced cardiomyocyte apoptosis.
Zhang
Jia-Ping
JP
State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Burns Research, Southwest Hospital, Third Military Medical University, Chongqing, PR China. japzhang@yahoo.com.cn
Ying
Xi
X
Liang
Wan-Yi
WY
Luo
Zhong-Hua
ZH
Yang
Zong-Cheng
ZC
Huang
Yue-Sheng
YS
Wang
Wen-Chang
WC
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002056:Burns / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*; D053148:Caspase 3 / Q000378:metabolism; D053938:DNA Fragmentation; D006331:Heart Diseases / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D020287:In Situ Nick-End Labeling; D053583:Interleukin-1beta / Q000378:metabolism; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000502:physiology*; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; D009195:Peroxidase; D048051:p38 Mitogen-Activated Protein Kinases; D053148:Caspase 3