PMID- 18408129
OWN - NLM
STAT- MEDLINE
DCOM- 20080815
LR  - 20200930
IS  - 0363-6135 (Print)
IS  - 0363-6135 (Linking)
VI  - 294
IP  - 6
DP  - 2008 Jun
TI  - Role of glucose metabolism in the recovery of postischemic LV mechanical 
      function: effects of insulin and other metabolic modulators.
PG  - H2576-86
LID - 10.1152/ajpheart.00942.2007 [doi]
AB  - The role of proton (H+) production from glucose metabolism in the recovery of 
      myocardial function during postischemic reperfusion and its alteration by insulin 
      and other metabolic modulators were examined. Rat hearts were perfused in vitro 
      with Krebs-Henseleit solution containing palmitate (1.2 mmol/l) and glucose (11 
      mmol/l) under nonischemic conditions or during reperfusion following no-flow 
      ischemia. Perfusate contained normal insulin (n-Ins, 50 mU/l), zero insulin 
      (0-Ins), or supplemental insulin (s-Ins, 1,000 mU/l) or other metabolic 
      modulators [dichloroacetate (DCA) at 3 mmol/l, oxfenicine at 1 mmol/l, and 
      N6-cyclohexyladenosine (CHA) at 0.5 micromol/l]. Relative to n-Ins, 0-Ins 
      depressed rates of glycolysis and glucose oxidation in nonischemic hearts and 
      impaired recovery of postischemic function. Relative to n-Ins, s-Ins did not 
      affect aerobic glucose metabolism and did not improve recovery when present 
      during reperfusion. When present during ischemia and reperfusion, s-Ins impaired 
      recovery. Combinations of metabolic modulators with s-Ins stimulated glucose 
      oxidation approximately 2.5-fold in nonischemic hearts and reduced H+ production. 
      DCA and CHA, in combination with s-Ins, improved recovery of function, but 
      addition of oxfenicine to this combination provided no further benefit. Although 
      DCA and CHA were each partially protective in hearts perfused with n-Ins, optimal 
      protection was achieved with DCA + CHA; recovery of function was inversely 
      proportional to H+ production during reperfusion. Although supplemental insulin 
      is not beneficial, elimination of H+ production from glucose metabolism by 
      simultaneous inhibition of glycolysis and stimulation of glucose oxidation 
      optimizes recovery of postischemic mechanical function.
FAU - Gandhi, Manoj
AU  - Gandhi M
AD  - Department of Pharmacology, Faculty of Medicine and Dentistry, University of 
      Alberta, Edmonton, Alberta, Canada.
FAU - Finegan, Barry A
AU  - Finegan BA
FAU - Clanachan, Alexander S
AU  - Clanachan AS
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080411
PL  - United States
TA  - Am J Physiol Heart Circ Physiol
JT  - American journal of physiology. Heart and circulatory physiology
JID - 100901228
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Insulin)
RN  - 2V16EO95H1 (Palmitic Acid)
RN  - 36396-99-3 (N(6)-cyclohexyladenosine)
RN  - 7UYG7X0F53 (4-hydroxyphenylglycine)
RN  - 9LSH52S3LQ (Dichloroacetic Acid)
RN  - IY9XDZ35W2 (Glucose)
RN  - K72T3FS567 (Adenosine)
RN  - TE7660XO1C (Glycine)
SB  - IM
MH  - Adenosine/analogs & derivatives/pharmacology
MH  - Animals
MH  - Dichloroacetic Acid/pharmacology
MH  - *Energy Metabolism/drug effects
MH  - Enzyme Inhibitors/pharmacology
MH  - Glucose/*metabolism
MH  - Glycine/analogs & derivatives/pharmacology
MH  - Glycolysis
MH  - Hydrogen-Ion Concentration
MH  - In Vitro Techniques
MH  - Insulin/*metabolism
MH  - Myocardial Ischemia/*complications/metabolism
MH  - Myocardial Reperfusion Injury/etiology/*metabolism
MH  - Myocardium/*metabolism
MH  - Palmitic Acid/metabolism
MH  - Perfusion
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Time Factors
MH  - Ventricular Dysfunction, Left/etiology/*metabolism
EDAT- 2008/04/15 09:00
MHDA- 2008/08/16 09:00
CRDT- 2008/04/15 09:00
PHST- 2008/04/15 09:00 [pubmed]
PHST- 2008/08/16 09:00 [medline]
PHST- 2008/04/15 09:00 [entrez]
AID - 00942.2007 [pii]
AID - 10.1152/ajpheart.00942.2007 [doi]
PST - ppublish
SO  - Am J Physiol Heart Circ Physiol. 2008 Jun;294(6):H2576-86. doi: 
      10.1152/ajpheart.00942.2007. Epub 2008 Apr 11.