PMID- 14715509
OWN - NLM
STAT- MEDLINE
DCOM- 20040521
LR  - 20220316
IS  - 0363-6135 (Print)
IS  - 0363-6135 (Linking)
VI  - 286
IP  - 5
DP  - 2004 May
TI  - Differential contribution of necrosis and apoptosis in myocardial 
      ischemia-reperfusion injury.
PG  - H1923-35
AB  - Necrosis and apoptosis differentially contribute to myocardial injury. 
      Determination of the contribution of these processes in ischemia-reperfusion 
      injury would allow for the preservation of myocardial tissue. Necrosis and 
      apoptosis were investigated in Langendorff-perfused rabbit hearts (n = 47) 
      subjected to 0 (Control group), 5 (GI-5), 10 (GI-10), 15 (GI-15), 20 (GI-20), 25 
      (GI-25), and 30 min (GI-30) of global ischemia (GI) and 120 min of reperfusion. 
      Myocardial injury was determined by triphenyltetrazolium chloride (TTC) staining, 
      terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL), 
      bax, bcl2, poly(ADP)ribose polymerase (PARP) cleavage, caspase-3, -8, and -9 
      cleavage and activity, Fas ligand (FasL), and Fas-activated death domain (FADD). 
      The contribution of apoptosis was determined separately (n = 42) using 
      irreversible caspase-3, -8, and -9 inhibitors. Left ventricular peak developed 
      pressure (LVPDP) and systolic shortening (SS) were significantly decreased and 
      infarct size and TUNEL-positive cells were significantly increased (P < 0.05 vs. 
      Control group) at GI-20, GI-25, and GI-30. Proapoptotic bax, PARP cleavage, and 
      caspase-3 and -9 cleavage and activity were apparent at GI-5 to GI-30. Fas, FADD, 
      and caspase-8 cleavage and activity were unaltered. Irreversible inhibition of 
      caspase-3 and -9 activity significantly decreased (P < 0.05) infarct size at 
      GI-25 and GI-30 but had no effect on LVPDP or SS. Myocardial injury results from 
      a significant increase in both necrosis and apoptosis (P < 0.05 vs. Control 
      group) evident by TUNEL, TTC staining, and caspase activity at GI-20. Intrinsic 
      proapoptotic activation is evident early during ischemia but does not 
      significantly contribute to infarct size before GI-25. The contribution of 
      necrosis to infarct size at GI-20, GI-25, and GI-30 is significantly greater than 
      that of apoptosis. Apoptosis is significantly decreased by caspase inhibition 
      during early reperfusion, but this protection does not improve immediate 
      postischemic functional recovery.
FAU - McCully, James D
AU  - McCully JD
AD  - Division of Cardiothoracic Surgery, Beth Israel Deaconess Medical Center and 
      Harvard Medical School, Boston, Massachusetts 02115, USA. 
      james_mccully@hms.harvard.edu
FAU - Wakiyama, Hidetaka
AU  - Wakiyama H
FAU - Hsieh, Yng-Ju
AU  - Hsieh YJ
FAU - Jones, Mara
AU  - Jones M
FAU - Levitsky, Sidney
AU  - Levitsky S
LA  - eng
GR  - R01 HL029077/HL/NHLBI NIH HHS/United States
GR  - HL-29077/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20040108
PL  - United States
TA  - Am J Physiol Heart Circ Physiol
JT  - American journal of physiology. Heart and circulatory physiology
JID - 100901228
RN  - 0 (Caspase Inhibitors)
RN  - 0 (Cysteine Proteinase Inhibitors)
RN  - 0 (Oligopeptides)
RN  - 0 (benzoylcarbonyl-aspartyl-glutamyl-valyl-aspartyl-fluoromethyl ketone)
RN  - 0 (benzyloxycarbonyl-isoleucyl-glutamyl-threonyl-aspartic acid fluoromethyl 
      ketone)
RN  - 0 (benzyloxycarbonyl-leucyl-glutamyl-histidyl-aspartic acid fluoromethyl ketone)
RN  - EC 3.4.22.- (Caspases)
SB  - IM
MH  - Animals
MH  - *Apoptosis
MH  - Caspase Inhibitors
MH  - Caspases/chemistry
MH  - Cysteine Proteinase Inhibitors/pharmacology
MH  - Hemodynamics
MH  - In Situ Nick-End Labeling
MH  - Myocardial Contraction
MH  - Myocardial Infarction/pathology
MH  - Myocardial Ischemia/*pathology/*physiopathology
MH  - Myocardial Reperfusion Injury/*pathology/*physiopathology
MH  - Necrosis
MH  - Oligopeptides/pharmacology
MH  - Rabbits
MH  - Recovery of Function
EDAT- 2004/01/13 05:00
MHDA- 2004/05/22 05:00
CRDT- 2004/01/13 05:00
PHST- 2004/01/13 05:00 [pubmed]
PHST- 2004/05/22 05:00 [medline]
PHST- 2004/01/13 05:00 [entrez]
AID - 00935.2003 [pii]
AID - 10.1152/ajpheart.00935.2003 [doi]
PST - ppublish
SO  - Am J Physiol Heart Circ Physiol. 2004 May;286(5):H1923-35. doi: 
      10.1152/ajpheart.00935.2003. Epub 2004 Jan 8.