title: Role of mechanical stress in the form of cardiomyocyte death during the early phase of reperfusion.
abstract: 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.
authors.affiliation: Cardiovascular Center, Kansai Medical University, Moriguchi, Japan. otanih@takii.kmu.ac.jp
authors.forename: Hajime
authors.initials: H
authors.lastname: Otani
authors.forename: Seiji
authors.initials: S
authors.lastname: Matsuhisa
authors.forename: Yuzo
authors.initials: Y
authors.lastname: Akita
authors.forename: Shiori
authors.initials: S
authors.lastname: Kyoi
authors.forename: Chiharu
authors.initials: C
authors.lastname: Enoki
authors.forename: Kimiko
authors.initials: K
authors.lastname: Tatsumi
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Fujiwara
authors.forename: Reiji
authors.initials: R
authors.lastname: Hattori
authors.forename: Hiroji
authors.initials: H
authors.lastname: Imamura
authors.forename: Toshiji
authors.initials: T
authors.lastname: Iwasaka
mesh_terms: 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