PMID- 19298539
OWN - NLM
STAT- MEDLINE
DCOM- 20121227
LR  - 20181201
IS  - 1440-1681 (Electronic)
IS  - 0305-1870 (Linking)
VI  - 36
IP  - 9
DP  - 2009 Sep
TI  - Hypoxia inducible factor-1 improves the actions of positive inotropic agents in 
      stunned cardiac myocytes.
PG  - 904-11
LID - 10.1111/j.1440-1681.2009.05165.x [doi]
AB  - 1. In the present study, we tested hypothesis that upregulation of 
      hypoxia-inducible factor-1 (HIF-1) would improve the actions of positive 
      inotropic agents in cardiac myocytes after simulated ischaemia-reperfusion (I/R). 
      2. Hypoxia-inducible factor-1alpha was upregulated with deferoxamine (150 mg/kg per 
      day for 2 days). Rabbit cardiac myocytes were subjected to simulated ischaemia 
      (15 min, 95% N(2)-5% CO2) and reperfusion (re-oxygenation) and compared with 
      control myocytes. Cell contraction and calcium transients were measured at 
      baseline and after forskolin (10(-7) and 10(-6) mol/L) or ouabain (10(-5) and 
      10(-4) mol/L). 3. Under control conditions, high-dose forskolin and ouabain 
      increased percentage shortening by 20 and 18%, respectively. Deferoxamine-treated 
      control myocytes responded similarly. In stunned myocytes, forskolin and ouabain 
      did not significantly increase shortening (increases of 8% and 9%, respectively). 
      Deferoxamine restored the effects of forskolin (+26%) and ouabain (+28%) in 
      stunning. The results for maximum shortening and relaxation rates were similar. 
      The increased calcium transients caused by forskolin and ouabain were also 
      depressed in stunned myocytes, but were maintained by HIF-1 upregulation. 4. 
      These results suggest that simulated I/R impaired the functional and calcium 
      transient effects of positive inotropic agents. Upregulation of HIF-1 protects 
      cardiac myocyte function after I/R by maintaining calcium release.
FAU - Tan, Tao
AU  - Tan T
AD  - Heart and Brain Circulation Laboratory, Department of Physiology and Biophysics, 
      University of Medicine and Dentistry of New Jersey Robert Wood Johnson Medical 
      School Piscataway, NJ 08854, USA.
FAU - Luciano, Jason A
AU  - Luciano JA
FAU - Scholz, Peter M
AU  - Scholz PM
FAU - Weiss, Harvey R
AU  - Weiss HR
LA  - eng
GR  - HL 40320/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20090302
PL  - Australia
TA  - Clin Exp Pharmacol Physiol
JT  - Clinical and experimental pharmacology & physiology
JID - 0425076
RN  - 0 (Antifungal Agents)
RN  - 0 (Cardiotonic Agents)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Iron Chelating Agents)
RN  - 0 (Pyridones)
RN  - 19W019ZDRJ (Ciclopirox)
RN  - 1F7A44V6OU (Colforsin)
RN  - 5ACL011P69 (Ouabain)
RN  - J06Y7MXW4D (Deferoxamine)
SB  - IM
MH  - Animals
MH  - Antifungal Agents/pharmacology
MH  - Calcium Signaling/drug effects
MH  - Cardiotonic Agents/*pharmacology
MH  - Ciclopirox
MH  - Colforsin/pharmacology
MH  - Deferoxamine/pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/*metabolism
MH  - Iron Chelating Agents/pharmacology
MH  - Myocardial Contraction/*drug effects
MH  - Myocardial Stunning/*metabolism/physiopathology
MH  - Myocytes, Cardiac/*drug effects/metabolism
MH  - Ouabain/pharmacology
MH  - Pyridones/pharmacology
MH  - Rabbits
MH  - Reperfusion Injury/*metabolism/physiopathology
MH  - Time Factors
MH  - Up-Regulation
EDAT- 2009/03/21 09:00
MHDA- 2012/12/28 06:00
CRDT- 2009/03/21 09:00
PHST- 2009/03/21 09:00 [entrez]
PHST- 2009/03/21 09:00 [pubmed]
PHST- 2012/12/28 06:00 [medline]
AID - CEP5165 [pii]
AID - 10.1111/j.1440-1681.2009.05165.x [doi]
PST - ppublish
SO  - Clin Exp Pharmacol Physiol. 2009 Sep;36(9):904-11. doi: 
      10.1111/j.1440-1681.2009.05165.x. Epub 2009 Mar 2.