title: Reduction in hemoglobin-oxygen affinity results in the improvement of exercise capacity in mice with chronic heart failure.
abstract: OBJECTIVE
  This study examined whether a reduction in hemoglobin-oxygen affinity improves exercise capacity in mice with heart failure.
  
  
  BACKGROUND
  Exercise intolerance is a major determinant of quality of life in patients with chronic heart failure. One of the major goals of the treatment for chronic heart failure is to improve quality of life.
  
  
  METHODS
  Four weeks after left coronary ligation, we transplanted bone marrow cells isolated from the transgenic mice expressing a hemoglobin variant with low oxygen affinity, Presbyterian, into the lethally irradiated mice with heart failure or administered a synthetic allosteric modifier of hemoglobin. The mice were then exercised on a treadmill.
  
  
  RESULTS
  Four weeks after the left coronary artery ligation, mice showed cardiac dysfunction and chamber dilation, which were characteristics of heart failure. The transplantation led to a reduction in hemoglobin-oxygen affinity and an increase in oxygen supply for skeletal muscle without changes in muscle properties. The transplanted mice showed improved running performance on a treadmill despite impaired cardiac contractility. Furthermore, administration of the synthetic allosteric modifier of hemoglobin showed a similar effect.
  
  
  CONCLUSIONS
  Allosteric modification of hemoglobin represents a therapeutic option for improving exercise capacity in patients with chronic heart failure. One mechanism of improvement in exercise capacity is enhanced oxygen delivery in the skeletal muscle.
authors: Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Osaka, Japan.
authors: Tetsuya
authors: T
authors: Watanabe
authors: Toshihiro
authors: T
authors: Takeda
authors: Shigemiki
authors: S
authors: Omiya
authors: Shungo
authors: S
authors: Hikoso
authors: Osamu
authors: O
authors: Yamaguchi
authors: Yuko
authors: Y
authors: Nakano
authors: Yoshiharu
authors: Y
authors: Higuchi
authors: Atsuko
authors: A
authors: Nakai
authors: Yusuke
authors: Y
authors: Abe
authors: Yayoi
authors: Y
authors: Aki-Jin
authors: Masayuki
authors: M
authors: Taniike
authors: Isamu
authors: I
authors: Mizote
authors: Yasushi
authors: Y
authors: Matsumura
authors: Takahiko
authors: T
authors: Shimizu
authors: Kazuhiko
authors: K
authors: Nishida
authors: Kiyohiro
authors: K
authors: Imai
authors: Masatsugu
authors: M
authors: Hori
authors: Takuji
authors: T
authors: Shirasawa
authors: Kinya
authors: K
authors: Otsu
mesh_terms: D000814:Aniline Compounds / Q000627:therapeutic use*; D000818:Animals; D000986:Antisickling Agents / Q000627:therapeutic use*; D017079:Exercise Tolerance / Q000502:physiology*; D005914:Globins / Q000378:metabolism*; D006333:Heart Failure / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000378:metabolism; D010101:Oxygen Consumption / Q000502:physiology*; D011422:Propionates / Q000627:therapeutic use*
chemical_list: D000814:Aniline Compounds; D000986:Antisickling Agents; D011422:Propionates; D005914:Globins; C067396:efaproxiral