PMID- 31151453
OWN - NLM
STAT- MEDLINE
DCOM- 20200224
LR  - 20200309
IS  - 1475-2840 (Electronic)
IS  - 1475-2840 (Linking)
VI  - 18
IP  - 1
DP  - 2019 May 31
TI  - Impact of hyperglycemia on myocardial ischemia-reperfusion susceptibility and 
      ischemic preconditioning in hearts from rats with type 2 diabetes.
PG  - 66
LID - 10.1186/s12933-019-0872-7 [doi]
LID - 66
AB  - BACKGROUND: The mechanisms underlying increased mortality in patients with 
      diabetes and admission hyperglycemia after an acute coronary syndrome may involve 
      reduced capacity for cardioprotection. We investigated the impact of 
      hyperglycemia on exogenously activated cardioprotection by ischemic 
      preconditioning (IPC) in hearts from rats with type 2 diabetes mellitus (T2DM) 
      that were endogenously cardioprotected by an inherent mechanism, and the 
      involvement of myocardial glucose uptake (MGU) and myocardial O-linked 
      beta-N-acetylglucosamine (O-GlcNAc). METHODS AND RESULTS: In isolated, perfused rat 
      hearts subjected to ischemia-reperfusion, infarct size (IS) was overall larger 
      during hyper- ([Glucose] = 22 mmol/L]) than normoglycemia 
      ([Glucose] = 11 mmol/L]) (p < 0.001). IS was smaller in 12-week old Zucker 
      diabetic fatty rats with recent onset T2DM (fa/fa) than in rats without T2DM 
      (fa/+) (n = 8 in each group) both during hyperglycemia (p < 0.05) and 
      normoglycemia (p < 0.05). IPC (2 x 5 min cycles) reduced IS during normo- 
      (p < 0.01 for both groups) but not during hyperglycemia independently of the 
      presence of T2DM. During hyperglycemia, an intensified IPC stimulus (4 x 5 min 
      cycles) reduced IS only in hearts from animals with T2DM (p < 0.05). IPC 
      increased MGU and O-GlcNAc levels during reperfusion in animals with and without 
      T2DM at normoglycemia (MGU: p < 0.05, O-GlcNAc: p < 0.01 for both groups) but not 
      during hyperglycemia. Intensified IPC at hyperglycemia increased MGU (p < 0.05) 
      and O-GlcNAc levels (p < 0.05) only in hearts from animals with T2DM. CONCLUSION: 
      While the effect of IPC is reduced during hyperglycemia in rats without T2DM, 
      endogenous cardioprotection in animals with T2DM is not influenced by 
      hyperglycemia and the capacity for exogenous cardioprotection by IPC is 
      preserved. MGU and O-GlcNAc levels are increased by exogenously induced 
      cardioprotection by IPC but not by endogenous cardioprotection in animals with 
      T2DM reflecting different underlying mechanisms by exogenous and endogenous 
      cardioprotection.
FAU - Kristiansen, Steen Buus
AU  - Kristiansen SB
AUID- ORCID: 0000-0001-5565-0914
AD  - Department of Cardiology, Aarhus University Hospital, Skejby Sygehus, Palle 
      Juul-Jensens Boulevard 99, 8200, Aarhus N, Denmark. sbk@clin.au.dk.
FAU - Paelestik, Kim Bolther
AU  - Paelestik KB
AD  - Department of Cardiology, Aarhus University Hospital, Skejby Sygehus, Palle 
      Juul-Jensens Boulevard 99, 8200, Aarhus N, Denmark.
FAU - Johnsen, Jacob
AU  - Johnsen J
AD  - Department of Cardiology, Aarhus University Hospital, Skejby Sygehus, Palle 
      Juul-Jensens Boulevard 99, 8200, Aarhus N, Denmark.
FAU - Jespersen, Nichlas Riise
AU  - Jespersen NR
AD  - Department of Cardiology, Aarhus University Hospital, Skejby Sygehus, Palle 
      Juul-Jensens Boulevard 99, 8200, Aarhus N, Denmark.
FAU - Pryds, Kasper
AU  - Pryds K
AD  - Department of Cardiology, Aarhus University Hospital, Skejby Sygehus, Palle 
      Juul-Jensens Boulevard 99, 8200, Aarhus N, Denmark.
FAU - Hjortbak, Marie Vognstoft
AU  - Hjortbak MV
AD  - Department of Cardiology, Aarhus University Hospital, Skejby Sygehus, Palle 
      Juul-Jensens Boulevard 99, 8200, Aarhus N, Denmark.
FAU - Jensen, Rebekka Vibjerg
AU  - Jensen RV
AD  - Department of Cardiology, Aarhus University Hospital, Skejby Sygehus, Palle 
      Juul-Jensens Boulevard 99, 8200, Aarhus N, Denmark.
FAU - Botker, Hans Erik
AU  - Botker HE
AD  - Department of Cardiology, Aarhus University Hospital, Skejby Sygehus, Palle 
      Juul-Jensens Boulevard 99, 8200, Aarhus N, Denmark.
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190531
PL  - England
TA  - Cardiovasc Diabetol
JT  - Cardiovascular diabetology
JID - 101147637
RN  - 0 (Biomarkers)
RN  - 0 (Blood Glucose)
RN  - EC 3.2.1.50 (hexosaminidase C)
RN  - EC 3.2.1.52 (beta-N-Acetylhexosaminidases)
RN  - V956696549 (Acetylglucosamine)
SB  - IM
MH  - Acetylglucosamine/metabolism
MH  - Animals
MH  - Biomarkers/blood
MH  - Blood Glucose/*metabolism
MH  - Diabetes Mellitus, Type 2/*blood/complications
MH  - Disease Models, Animal
MH  - *Ischemic Preconditioning, Myocardial
MH  - Isolated Heart Preparation
MH  - Myocardial Infarction/blood/etiology/pathology/*prevention & control
MH  - Myocardial Reperfusion Injury/blood/etiology/pathology/*prevention & control
MH  - Myocardium/*metabolism/pathology
MH  - Rats, Zucker
MH  - beta-N-Acetylhexosaminidases/metabolism
PMC - PMC6543682
OTO - NOTNLM
OT  - Hyperglycemia
OT  - Infarction
OT  - Ischemia
OT  - O-GlcNAc
OT  - Reperfusion
OT  - Type 2 diabetes mellitus
COIS- The authors declare that they have no competing interests.
EDAT- 2019/06/04 06:00
MHDA- 2020/02/25 06:00
PMCR- 2019/05/31
CRDT- 2019/06/02 06:00
PHST- 2019/03/02 00:00 [received]
PHST- 2019/05/20 00:00 [accepted]
PHST- 2019/06/02 06:00 [entrez]
PHST- 2019/06/04 06:00 [pubmed]
PHST- 2020/02/25 06:00 [medline]
PHST- 2019/05/31 00:00 [pmc-release]
AID - 10.1186/s12933-019-0872-7 [pii]
AID - 872 [pii]
AID - 10.1186/s12933-019-0872-7 [doi]
PST - epublish
SO  - Cardiovasc Diabetol. 2019 May 31;18(1):66. doi: 10.1186/s12933-019-0872-7.