Altered myocardial Ca(2+) and Na(+) handling in congestive heart failure
(CHF) may be expected to decrease the tolerance to ischemia by augmenting
reperfusion Ca(2+) overload. The aim of the present study was to
investigate tolerance to hypoxia-reoxygenation by measuring enzyme
release, cell death, ATP level, and cell Ca(2+) and Na(+) in cardiomyocytes
from failing rat hearts. CHF was induced in Wistar rats by ligation
of the left coronary artery during isoflurane anesthesia, after which
cardiac failure developed within 6 wk. Isolated cardiomyocytes were
cultured for 24 h and subsequently exposed to 4 h of hypoxia and
2 h of reoxygenation. Cell damage was measured as lactate dehydrogenase
(LD) release, cell death as propidium iodide uptake, and ATP by firefly
luciferase assay. Cell Ca(2+) and Na(+) were determined with radioactive
isotopes, and free intracellular Ca(2+) concentration (Ca(2+)(i))
with fluo-3 AM. CHF cells showed less increase in LD release and
cell death after hypoxia-reoxygenation and had less relative reduction
in ATP level after hypoxia than sham cells. CHF cells accumulated
less Na(+) than sham cells during hypoxia (117 vs. 267 nmol/mg protein).
CHF cells maintained much lower Ca(2+)(i) than sham cells during
hypoxia (423 vs. 1,766 arbitrary units at 4 h of hypoxia), and exchangeable
Ca(2+) increased much less in CHF than in sham cells (1.4 vs. 6.7
nmol/mg protein) after 120 min of reoxygenation. Ranolazine, an inhibitor
of late Na(+) current, significantly attenuated both the increase
in exchangeable Ca(2+) and the increase in LD release in sham cells
after reoxygenation. This supports the suggestion that differences
in Na(+) accumulation during hypoxia cause the observed differences
in Ca(2+) accumulation during reoxygenation. Tolerance to hypoxia
and reoxygenation was surprisingly higher in CHF than in sham cardiomyocytes,
probably explained by lower hypoxia-mediated Na(+) accumulation and
subsequent lower Ca(2+) accumulation in CHF after reoxygenation.
%0 Journal Article
%1 Shar_2009_787
%A Sharikabad, Mohammad Nouri
%A Aronsen, Jan Magnus
%A Haugen, Espen
%A Pedersen, Janne
%A M�ller, Anne-Sophie W
%A M�rk, Halvor Kjeang
%A Aass, Hans C D
%A Sejersted, Ole M
%A Sjaastad, Ivar
%A Br�rs, Odd
%D 2009
%J Am J Physiol Heart Circ Physiol
%K /&/ ATPase, Acetanilides, Adenosine Animal; Animals; Blockers, Calcium, Cardiac, Cell Cells, Channel Cultured; Death; Dehydrogenase, Disease Exchanger, Factors Failure, Heart Hypoxia; Infarction, Injury, L-Lactate Male; Models, Myocardial Myocytes, Oxygen, Piperazines, Potassium, Radioisotopes; Rats, Rats; Reperfusion Rubidium Sodium Sodium, Sodium-Calcium Sodium-Potassium-Exchanging Time Triphosphate, Wistar; complications/metabolism/pathology; control; drug effects/enzymology/metabolism/pathology; etiology/metabolism/pathology; etiology/metabolism/prevention metabolism; pharmacology;
%N 3
%P H787--H795
%R 10.1152/ajpheart.00796.2008
%T Cardiomyocytes from postinfarction failing rat hearts have improved
ischemia tolerance.
%U http://dx.doi.org/10.1152/ajpheart.00796.2008
%V 296
%X Altered myocardial Ca(2+) and Na(+) handling in congestive heart failure
(CHF) may be expected to decrease the tolerance to ischemia by augmenting
reperfusion Ca(2+) overload. The aim of the present study was to
investigate tolerance to hypoxia-reoxygenation by measuring enzyme
release, cell death, ATP level, and cell Ca(2+) and Na(+) in cardiomyocytes
from failing rat hearts. CHF was induced in Wistar rats by ligation
of the left coronary artery during isoflurane anesthesia, after which
cardiac failure developed within 6 wk. Isolated cardiomyocytes were
cultured for 24 h and subsequently exposed to 4 h of hypoxia and
2 h of reoxygenation. Cell damage was measured as lactate dehydrogenase
(LD) release, cell death as propidium iodide uptake, and ATP by firefly
luciferase assay. Cell Ca(2+) and Na(+) were determined with radioactive
isotopes, and free intracellular Ca(2+) concentration (Ca(2+)(i))
with fluo-3 AM. CHF cells showed less increase in LD release and
cell death after hypoxia-reoxygenation and had less relative reduction
in ATP level after hypoxia than sham cells. CHF cells accumulated
less Na(+) than sham cells during hypoxia (117 vs. 267 nmol/mg protein).
CHF cells maintained much lower Ca(2+)(i) than sham cells during
hypoxia (423 vs. 1,766 arbitrary units at 4 h of hypoxia), and exchangeable
Ca(2+) increased much less in CHF than in sham cells (1.4 vs. 6.7
nmol/mg protein) after 120 min of reoxygenation. Ranolazine, an inhibitor
of late Na(+) current, significantly attenuated both the increase
in exchangeable Ca(2+) and the increase in LD release in sham cells
after reoxygenation. This supports the suggestion that differences
in Na(+) accumulation during hypoxia cause the observed differences
in Ca(2+) accumulation during reoxygenation. Tolerance to hypoxia
and reoxygenation was surprisingly higher in CHF than in sham cardiomyocytes,
probably explained by lower hypoxia-mediated Na(+) accumulation and
subsequent lower Ca(2+) accumulation in CHF after reoxygenation.
@article{Shar_2009_787,
abstract = {Altered myocardial Ca(2+) and Na(+) handling in congestive heart failure
(CHF) may be expected to decrease the tolerance to ischemia by augmenting
reperfusion Ca(2+) overload. The aim of the present study was to
investigate tolerance to hypoxia-reoxygenation by measuring enzyme
release, cell death, ATP level, and cell Ca(2+) and Na(+) in cardiomyocytes
from failing rat hearts. CHF was induced in Wistar rats by ligation
of the left coronary artery during isoflurane anesthesia, after which
cardiac failure developed within 6 wk. Isolated cardiomyocytes were
cultured for 24 h and subsequently exposed to 4 h of hypoxia and
2 h of reoxygenation. Cell damage was measured as lactate dehydrogenase
(LD) release, cell death as propidium iodide uptake, and ATP by firefly
luciferase assay. Cell Ca(2+) and Na(+) were determined with radioactive
isotopes, and free intracellular Ca(2+) concentration ([Ca(2+)](i))
with fluo-3 AM. CHF cells showed less increase in LD release and
cell death after hypoxia-reoxygenation and had less relative reduction
in ATP level after hypoxia than sham cells. CHF cells accumulated
less Na(+) than sham cells during hypoxia (117 vs. 267 nmol/mg protein).
CHF cells maintained much lower [Ca(2+)](i) than sham cells during
hypoxia (423 vs. 1,766 arbitrary units at 4 h of hypoxia), and exchangeable
Ca(2+) increased much less in CHF than in sham cells (1.4 vs. 6.7
nmol/mg protein) after 120 min of reoxygenation. Ranolazine, an inhibitor
of late Na(+) current, significantly attenuated both the increase
in exchangeable Ca(2+) and the increase in LD release in sham cells
after reoxygenation. This supports the suggestion that differences
in Na(+) accumulation during hypoxia cause the observed differences
in Ca(2+) accumulation during reoxygenation. Tolerance to hypoxia
and reoxygenation was surprisingly higher in CHF than in sham cardiomyocytes,
probably explained by lower hypoxia-mediated Na(+) accumulation and
subsequent lower Ca(2+) accumulation in CHF after reoxygenation.},
added-at = {2009-06-03T11:20:58.000+0200},
author = {Sharikabad, Mohammad Nouri and Aronsen, Jan Magnus and Haugen, Espen and Pedersen, Janne and M�ller, Anne-Sophie W and M�rk, Halvor Kjeang and Aass, Hans C D and Sejersted, Ole M and Sjaastad, Ivar and Br�rs, Odd},
biburl = {https://www.bibsonomy.org/bibtex/2497878c2e64f45e5ed33f39445dd5a61/hake},
description = {The whole bibliography file I use.},
doi = {10.1152/ajpheart.00796.2008},
file = {Shar_2009_787.pdf:Shar_2009_787.pdf:PDF},
institution = {Dept. of Clinical Chemistry, Ullev�l Univ. Hopital, 0407 Oslo, Norway.
m.n.sharikabad@medisin.uio.no},
interhash = {16d9360ce0773bcf8dd836712412523c},
intrahash = {497878c2e64f45e5ed33f39445dd5a61},
journal = {Am J Physiol Heart Circ Physiol},
keywords = {/&/ ATPase, Acetanilides, Adenosine Animal; Animals; Blockers, Calcium, Cardiac, Cell Cells, Channel Cultured; Death; Dehydrogenase, Disease Exchanger, Factors Failure, Heart Hypoxia; Infarction, Injury, L-Lactate Male; Models, Myocardial Myocytes, Oxygen, Piperazines, Potassium, Radioisotopes; Rats, Rats; Reperfusion Rubidium Sodium Sodium, Sodium-Calcium Sodium-Potassium-Exchanging Time Triphosphate, Wistar; complications/metabolism/pathology; control; drug effects/enzymology/metabolism/pathology; etiology/metabolism/pathology; etiology/metabolism/prevention metabolism; pharmacology;},
month = Mar,
number = 3,
pages = {H787--H795},
pdf = {Shar_2009_787.pdf},
pii = {00796.2008},
pmid = {19136604},
timestamp = {2009-06-03T11:21:30.000+0200},
title = {Cardiomyocytes from postinfarction failing rat hearts have improved
ischemia tolerance.},
url = {http://dx.doi.org/10.1152/ajpheart.00796.2008},
volume = 296,
year = 2009
}