PMID- 19098935
OWN - NLM
STAT- MEDLINE
DCOM- 20090421
LR  - 20211020
IS  - 1745-7254 (Electronic)
IS  - 1671-4083 (Print)
IS  - 1671-4083 (Linking)
VI  - 30
IP  - 1
DP  - 2009 Jan
TI  - Cardioprotection by polysaccharide sulfate against ischemia/reperfusion injury in 
      isolated rat hearts.
PG  - 54-60
LID - 10.1038/aps.2008.12 [doi]
AB  - AIM: Polysaccharide sulfate (PSS) is a new type of heparinoid synthesized with 
      alginic acid as the basic material and then by chemical introduction of effective 
      groups. Although PSS is successfully applied in ischemic cardio-cerebrovascular 
      disease, its effect on cardiac function after ischemia/reperfusion (I/R) injury 
      has previously not been investigated. The aim of the present study was to 
      investigate whether PSS can protect the heart from I/R injury and the underlying 
      mechanism of protection. METHODS: Isolated rat hearts were perfused (Langendorff) 
      and subjected to 20 min global ischemia followed by 60 min reperfusion with 
      Kreb's Henseleit solution or PSS (0.3-100 mg/L). Myocardial contractile function 
      was continuously recorded. Creatine kinase (CK) and lactate dehydrogenase (LDH) 
      leakage were measured. Tumor necrosis factor-alpha (TNF-alpha) expression in 
      cardiomyocytes was investigated. Western blot analysis for extracellular 
      regulated kinases (ERKs), c-jun amino-terminal kinase (JNKs) and p38 
      mitogen-activated protein kinase (MAPK) activity was performed. RESULTS: After 
      I/R, cardiac contractility decreased, CK and LDH levels increased in the coronary 
      effluent, and TNF-alpha expression increased in cardiomyocytes. PSS 
      administration at concentrations of 1-30 mg/L improved cardiac contractility, 
      reduced CK and LDH release and inhibited TNF-alpha production. 
      Phosphorylated-p38MAPK (p-p38MAPK) and p-p54/p46-JNK increased in I/R rat hearts 
      but diminished in PSS (1-30 mg/L) treated hearts. P-p44/p42-ERK levels were 
      unchanged. In contrast, high concentrations of PSS (100 mg/L) had adverse effects 
      that caused a worsening of heart function. CONCLUSION: PSS has dose-dependent 
      cardioprotective effects on the rat heart after I/R injury. The beneficial 
      effects may be mediated through normalization of the activity of p38 MAPK and JNK 
      pathways as well as controlling the level of TNF-alpha expression.
FAU - Yang, Ying
AU  - Yang Y
AD  - Institute of Cardiology, The First Affiliated Hospital, College of Medicine, 
      Zhejiang University, Hangzhou 310003, China.
FAU - Hu, Shen-jiang
AU  - Hu SJ
FAU - Li, Liang
AU  - Li L
FAU - Chen, Guo-ping
AU  - Chen GP
LA  - eng
PT  - Journal Article
DEP - 20081222
PL  - United States
TA  - Acta Pharmacol Sin
JT  - Acta pharmacologica Sinica
JID - 100956087
RN  - 0 (Cardiotonic Agents)
RN  - 0 (Polysaccharides)
RN  - 0 (Sulfates)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 1.1.1.27 (L-Lactate Dehydrogenase)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - EC 2.7.3.2 (Creatine Kinase)
SB  - IM
MH  - Animals
MH  - Cardiotonic Agents/*pharmacology
MH  - Creatine Kinase/metabolism
MH  - Extracellular Signal-Regulated MAP Kinases/metabolism
MH  - Heart/*drug effects/physiology
MH  - JNK Mitogen-Activated Protein Kinases/metabolism
MH  - L-Lactate Dehydrogenase/metabolism
MH  - MAP Kinase Signaling System/physiology
MH  - Myocardial Contraction/drug effects/physiology
MH  - Polysaccharides/chemistry/*pharmacology
MH  - Random Allocation
MH  - Rats
MH  - Reperfusion Injury/*prevention & control
MH  - Sulfates/chemistry/*pharmacology
MH  - Tumor Necrosis Factor-alpha/metabolism
MH  - p38 Mitogen-Activated Protein Kinases/metabolism
PMC - PMC4006537
EDAT- 2008/12/23 09:00
MHDA- 2009/04/22 09:00
PMCR- 2009/01/01
CRDT- 2008/12/23 09:00
PHST- 2008/12/23 09:00 [entrez]
PHST- 2008/12/23 09:00 [pubmed]
PHST- 2009/04/22 09:00 [medline]
PHST- 2009/01/01 00:00 [pmc-release]
AID - aps200812 [pii]
AID - 10.1038/aps.2008.12 [doi]
PST - ppublish
SO  - Acta Pharmacol Sin. 2009 Jan;30(1):54-60. doi: 10.1038/aps.2008.12. Epub 2008 Dec 
      22.