%0 Journal Article %1 Imah_2005_916 %A Imahashi, Kenichi %A Pott, Christian %A Goldhaber, Joshua I %A Steenbergen, Charles %A Philipson, Kenneth D %A Murphy, Elizabeth %D 2005 %J Circ. Res. %K 16179590 Action Animals, Ca, Calcium, Cardiac, Contraction, Energy Exchanger, Extramural, Gov't, Injury, Isoproterenol, Knockout, Metabolism, Mice, Myocardial Myocardium, Myocytes, N.I.H., Non-U.S. P.H.S., Phenotype, Potentials, Reperfusion Research Sarcolemma, Sodium, Sodium-Calcium Support, U.S. lcium, %N 9 %P 916--921 %R 10.1161/01.RES.0000187456.06162.cb %T Cardiac-specific ablation of the Na$^+$-Ca$^2+$ exchanger confers protection against ischemia/reperfusion injury. %U http://dx.doi.org/10.1161/01.RES.0000187456.06162.cb %V 97 %X During ischemia and reperfusion, with an increase in intracellular Na$^+$ and a depolarized membrane potential, Ca$^2+$ may enter the myocyte in exchange for intracellular Na$^+$ via reverse-mode Na$^+$-Ca$^2+$ exchange (NCX). To test the role of Ca$^2+$ entry via NCX during ischemia and reperfusion, we studied mice with cardiac-specific ablation of NCX (NCX-KO) and demonstrated that reverse-mode Ca$^2+$ influx is absent in the NCX-KO myocytes. Langendorff perfused hearts were subjected to 20 minutes of global ischemia followed by 2 hours of reperfusion, during which time we monitored high-energy phosphates using 31P-NMR and left-ventricular developed pressure. In another group of hearts, we monitored intracellular Na$^+$ using 23Na-NMR. Consistent with Ca$^2+$ entry via NCX during ischemia, we found that hearts lacking NCX exhibited less of a decline in ATP during ischemia, delayed ischemic contracture, and reduced maximum contracture. Furthermore, on reperfusion following ischemia, NCX-KO hearts had much less necrosis, better recovery of left-ventricular developed pressure, improved phosphocreatine recovery, and reduced Na$^+$ overload. The improved recovery of function following ischemia in NCX-KO hearts was not attributable to the reduced preischemic contractility in NCX-KO hearts, because when the preischemic workload was matched by treatment with isoproterenol, NCX-KO hearts still exhibited improved postischemic function compared with wild-type hearts. Thus, NCX-KO hearts were significantly protected against ischemia-reperfusion injury, suggesting that Ca$^2+$ entry via reverse-mode NCX is a major cause of ischemia/reperfusion injury.

@article{Imah_2005_916, abstract = {During ischemia and reperfusion, with an increase in intracellular {N}a$^{+}$ and a depolarized membrane potential, {C}a$^{2+}$ may enter the myocyte in exchange for intracellular {N}a$^{+}$ via reverse-mode {N}a$^{+}$-{C}a$^{2+}$ exchange (NCX). To test the role of {C}a$^{2+}$ entry via NCX during ischemia and reperfusion, we studied mice with cardiac-specific ablation of NCX (NCX-KO) and demonstrated that reverse-mode {C}a$^{2+}$ influx is absent in the NCX-KO myocytes. Langendorff perfused hearts were subjected to 20 minutes of global ischemia followed by 2 hours of reperfusion, during which time we monitored high-energy phosphates using 31P-NMR and left-ventricular developed pressure. In another group of hearts, we monitored intracellular {N}a$^{+}$ using 23Na-NMR. Consistent with {C}a$^{2+}$ entry via NCX during ischemia, we found that hearts lacking NCX exhibited less of a decline in ATP during ischemia, delayed ischemic contracture, and reduced maximum contracture. Furthermore, on reperfusion following ischemia, NCX-KO hearts had much less necrosis, better recovery of left-ventricular developed pressure, improved phosphocreatine recovery, and reduced {N}a$^{+}$ overload. The improved recovery of function following ischemia in NCX-KO hearts was not attributable to the reduced preischemic contractility in NCX-KO hearts, because when the preischemic workload was matched by treatment with isoproterenol, NCX-KO hearts still exhibited improved postischemic function compared with wild-type hearts. Thus, NCX-KO hearts were significantly protected against ischemia-reperfusion injury, suggesting that {C}a$^{2+}$ entry via reverse-mode NCX is a major cause of ischemia/reperfusion injury.}, added-at = {2009-06-03T11:20:58.000+0200}, author = {Imahashi, Kenichi and Pott, Christian and Goldhaber, Joshua I and Steenbergen, Charles and Philipson, Kenneth D and Murphy, Elizabeth}, biburl = {https://www.bibsonomy.org/bibtex/29188e73b83dc2ed734536b4d31608776/hake}, description = {The whole bibliography file I use.}, doi = {10.1161/01.RES.0000187456.06162.cb}, file = {Imah_2005_916.pdf:Imah_2005_916.pdf:PDF}, interhash = {29ee758291e71c13b7e9b1ac20b42f8e}, intrahash = {9188e73b83dc2ed734536b4d31608776}, journal = {Circ. Res.}, keywords = {16179590 Action Animals, Ca, Calcium, Cardiac, Contraction, Energy Exchanger, Extramural, Gov't, Injury, Isoproterenol, Knockout, Metabolism, Mice, Myocardial Myocardium, Myocytes, N.I.H., Non-U.S. P.H.S., Phenotype, Potentials, Reperfusion Research Sarcolemma, Sodium, Sodium-Calcium Support, U.S. lcium,}, month = Oct, number = 9, pages = {916--921}, pii = {01.RES.0000187456.06162.cb}, pmid = {16179590}, timestamp = {2009-06-03T11:21:16.000+0200}, title = {Cardiac-specific ablation of the {N}a$^{+}$-{C}a$^{2+}$ exchanger confers protection against ischemia/reperfusion injury.}, url = {http://dx.doi.org/10.1161/01.RES.0000187456.06162.cb}, volume = 97, year = 2005 }