-transparent.png){kind=logo}
One or more brief periods of ischemia, termed preconditioning, dramatically limits infarct size and reduces intracellular acidosis during subsequent ischemia, potentially via enhanced sarcolemmal proton efflux mechanisms. To test the hypothesis that preconditioning increases the functional activity of sodium-dependent proton efflux pathways, isolated rat hearts were subjected to 30 min of global ischemia with or without preconditioning. Intracellular sodium (Nai) was assessed using 23Na magnetic resonance spectroscopy, and the activity of the Na-H exchanger and Na-K-2Cl cotransporter was measured by transiently exposing the hearts to an acid load (NH4Cl washout). Creatine kinase release was reduced by greater than 60% in the preconditioned hearts (P < 0.05) and was associated with improved functional recovery on reperfusion. Preconditioning increased Nai by 6.24 +/- 2.04 U, resulting in a significantly higher level of Nai before ischemia than in the control hearts. Nai increased significantly at the onset of ischemia (8.48 +/- 1.21 vs. 2.57 +/- 0.81 U, preconditioned vs. control hearts; P < 0.01). Preconditioning did not reduce Nai accumulation during ischemia, but the decline in Nai during the first 5 min of reperfusion was significantly greater in the preconditioned than in the control hearts (13.48 +/- 1.73 vs. 2.54 +/- 0.41 U; P < 0.001). Exposure of preconditioned hearts to ethylisopropylamiloride or bumetanide in the last reperfusion period limited in the increase in Nai during ischemia and reduced the beneficial effects of preconditioning. After the NH4Cl prepulse, preconditioned hearts acidified significantly more than control hearts and had significantly more rapid recovery of pH (preconditioned, delta pH = 0.35 +/- 0.04 U over 5 min; control, delta pH = 0.15 +/- 0.02 U over 5 min). This rapid pH recovery was not affected by inhibition of the Na-K-2Cl cotransporter but was abolished by inhibition of the Na-H exchanger. These results demonstrate that preconditioning alters the kinetics of Nai accumulation during global ischemia as well as proton transport after NH4Cl washout. These observations are consistent with stimulation of the Na-K-2Cl cotransporter and Na-H exchanger by preconditioning.
R Ramasamy, and
H Liu, and
S Anderson, and
J Lundmark, and
S Schaefer
November 1995,
The American journal of physiology,
R Ramasamy, and
H Liu, and
S Anderson, and
J Lundmark, and
S Schaefer
January 2015,
International journal of clinical and experimental medicine,
R Ramasamy, and
H Liu, and
S Anderson, and
J Lundmark, and
S Schaefer
December 1995,
The Journal of pharmacology and experimental therapeutics,
R Ramasamy, and
H Liu, and
S Anderson, and
J Lundmark, and
S Schaefer
November 1995,
Journal of cardiovascular pharmacology,
R Ramasamy, and
H Liu, and
S Anderson, and
J Lundmark, and
S Schaefer
September 1996,
Zhongguo yao li xue bao = Acta pharmacologica Sinica,
R Ramasamy, and
H Liu, and
S Anderson, and
J Lundmark, and
S Schaefer
May 2004,
Canadian journal of physiology and pharmacology,
R Ramasamy, and
H Liu, and
S Anderson, and
J Lundmark, and
S Schaefer
June 1996,
Japanese circulation journal,
R Ramasamy, and
H Liu, and
S Anderson, and
J Lundmark, and
S Schaefer
January 2009,
Revista brasileira de cirurgia cardiovascular : orgao oficial da Sociedade Brasileira de Cirurgia Cardiovascular,
R Ramasamy, and
H Liu, and
S Anderson, and
J Lundmark, and
S Schaefer
April 2010,
Journal of anesthesia,
R Ramasamy, and
H Liu, and
S Anderson, and
J Lundmark, and
S Schaefer
March 2000,
Biochemical and biophysical research communications,
