PMID- 15094104
OWN - NLM
STAT- MEDLINE
DCOM- 20040507
LR  - 20040419
IS  - 0002-9149 (Print)
IS  - 0002-9149 (Linking)
VI  - 93
IP  - 8A
DP  - 2004 Apr 22
TI  - Nutritional supplementation with mixed essential amino acids enhances myocyte 
      survival, preserving mitochondrial functional capacity during 
      ischemia-reperfusion injury.
PG  - 35A-40A
AB  - In patients undergoing coronary surgery, the uptake of amino acids, which has 
      been shown to correlate with oxygen consumption, is a mechanism of cardiac 
      adaptation to the iatrogenic ischemia-reperfusion injury associated with 
      cardioplegic arrest. Based on these premises, we sought to determine whether oral 
      supplementation with mixed amino acids may protect the rat heart exposed to 
      ischemia-reperfusion and to address whether this hypothesized cardioprotection is 
      achieved, at least in part, through preservation of the energy-producing 
      properties of mitochondria. Sprague-Dawley rats were fed (by enteral route) a 
      liquid diet, with or without mixed essential amino acids (daily dose of 1 g/kg) 
      for 30 days. Hearts from anesthetized rats were perfused by the Langendorff 
      method and randomized to 3 groups. The control group was perfused with buffer for 
      60 minutes; the ischemia-reperfusion control and the amino acid-treated groups 
      were exposed to 35 minutes of ischemia, followed by 60 or 120 minutes of 
      reperfusion. Amino acid supplements minimized infarct size (22 +/- 1.8% vs 33 +/- 
      2.5%; p <0.05) and occurrence of cardiomyocyte apoptosis, as assessed by 
      co-localization of terminal deoxynucleotidyl transferase-mediated dUTP nick end 
      labeling (TUNEL) and caspase-3-positive staining (p <0.01). Long-term treatment 
      with amino acids also reduced the proportion of cardiomyocytes exhibiting 
      immunostaining for cleaved caspase-9 (p <0.01) but was ineffective on processing 
      of caspase-8. Similar results were obtained in the whole heart by caspase 
      activity assays (p <0.01). The lessened activation of caspase-9 detected in amino 
      acid-treated hearts paralleled a strong reduction in mitochondrial release of 
      cytochrome c. Adenosine triphosphate (ATP) content and rate of ATP production in 
      isolated mitochondria were reduced by >75% in control hearts after 2 hours of 
      reperfusion (p <0.05 vs control hearts); these values returned toward those of 
      the control group in hearts supplemented with amino acids (p <0.01). Finally, the 
      oxygen consumption rate in myocardial skinned bundles was markedly reduced in 
      ischemia-reperfusion control hearts and almost normalized in amino acid-treated 
      hearts (approximately 20% and 93% of the value for normoxic hearts; p <0.01). 
      These results suggest that oral amino acid supplementation attenuates the extent 
      of ischemia-reperfusion injury in the rat heart, through preservation of the 
      mitochondria-generated production of high-energy phosphates.
FAU - Scarabelli, Tiziano M
AU  - Scarabelli TM
AD  - Division of Cardiology, St. John Hospital and Medical Center, Wayne State 
      University, Detroit, Michigan, USA. tiziano.scarabelli@stjohn.org
FAU - Pasini, Evasio
AU  - Pasini E
FAU - Stephanou, Anastasis
AU  - Stephanou A
FAU - Chen-Scarabelli, Carol
AU  - Chen-Scarabelli C
FAU - Saravolatz, Louis
AU  - Saravolatz L
FAU - Knight, Richard A
AU  - Knight RA
FAU - Latchman, David S
AU  - Latchman DS
FAU - Gardin, Julius M
AU  - Gardin JM
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Am J Cardiol
JT  - The American journal of cardiology
JID - 0207277
RN  - 0 (Amino Acids, Essential)
RN  - 0 (Dietary Proteins)
SB  - IM
MH  - Amino Acids, Essential/*administration & dosage
MH  - Animals
MH  - Dietary Proteins/*administration & dosage
MH  - *Dietary Supplements
MH  - Male
MH  - Mitochondria/metabolism
MH  - Myocytes, Cardiac/metabolism
MH  - Oxygen Consumption
MH  - Random Allocation
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Reperfusion Injury/*diet therapy/pathology
EDAT- 2004/04/20 05:00
MHDA- 2004/05/08 05:00
CRDT- 2004/04/20 05:00
PHST- 2004/04/20 05:00 [pubmed]
PHST- 2004/05/08 05:00 [medline]
PHST- 2004/04/20 05:00 [entrez]
AID - S0002914903015145 [pii]
AID - 10.1016/j.amjcard.2003.11.008 [doi]
PST - ppublish
SO  - Am J Cardiol. 2004 Apr 22;93(8A):35A-40A. doi: 10.1016/j.amjcard.2003.11.008.