Role of mechanical stress in the form of cardiomyocyte death during the early phase of reperfusion.
BACKGROUND
The hypothesis that mechanical stress during reperfusion produces myocyte oncosis and inhibits apoptosis was tested in the present study.


RESULTS
Isolated and perfused rat hearts were subjected to 30 min ischemia followed by 150 min reperfusion. In the control-reperfusion heart, the form of myocyte death was a mixture of apoptosis only, oncosis only, and both apoptosis and oncosis. Apoptotic myocytes contained mitochondria that maintained membrane potential (Deltapsim), whereas oncotic myocytes contained only Deltapsim-collapsed mitochondria. Treatment with the contractile blocker 2,3-butanedione monoxime (BDM) during reperfusion increased caspase-3 activity and produced predominantly apoptosis. However, withdrawal of BDM provoked oncosis in terminal deoxynucleotide nick-end labeling (TUNEL)-positive myocytes. Myocardial stretch by inflating an intraventricular balloon at the time of reperfusion with BDM increased only oncotic myocytes, whereas the same mechanical stress 120 min after reperfusion increased oncotic myocytes positive for TUNEL. Increased mechanical stress at the time of reperfusion by treatment with isoproterenol or hyposmotic buffer inhibited caspase-3 activity and increased only oncotic myocytes. Co-treatment with the caspase-3 inhibitor, Ac-DEVD-CHO, and BDM during reperfusion inhibited myocyte apoptosis and oncosis but did not inhibit oncosis after withdrawal of BDM.


CONCLUSIONS
These results suggest that mechanical stress is a critical determinant of the form of myocyte death during the early phase of reperfusion.
Otani
Hajime
H
Cardiovascular Center, Kansai Medical University, Moriguchi, Japan. otanih@takii.kmu.ac.jp
Matsuhisa
Seiji
S
Akita
Yuzo
Y
Kyoi
Shiori
S
Enoki
Chiharu
C
Tatsumi
Kimiko
K
Fujiwara
Hiroyoshi
H
Hattori
Reiji
R
Imamura
Hiroji
H
Iwasaka
Toshiji
T
D000818:Animals; D017209:Apoptosis; D016923:Cell Death; D066298:In Vitro Techniques; D015428:Myocardial Reperfusion Injury / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000473:pathology*; D051381:Rats; D013314:Stress, Mechanical; D013997:Time Factors