Reduction in hemoglobin-oxygen affinity results in the improvement of exercise capacity in mice with chronic heart failure.
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.
Watanabe
Tetsuya
T
Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Osaka, Japan.
Takeda
Toshihiro
T
Omiya
Shigemiki
S
Hikoso
Shungo
S
Yamaguchi
Osamu
O
Nakano
Yuko
Y
Higuchi
Yoshiharu
Y
Nakai
Atsuko
A
Abe
Yusuke
Y
Aki-Jin
Yayoi
Y
Taniike
Masayuki
M
Mizote
Isamu
I
Matsumura
Yasushi
Y
Shimizu
Takahiko
T
Nishida
Kazuhiko
K
Imai
Kiyohiro
K
Hori
Masatsugu
M
Shirasawa
Takuji
T
Otsu
Kinya
K
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*
D000814:Aniline Compounds; D000986:Antisickling Agents; D011422:Propionates; D005914:Globins; C067396:efaproxiral