Ischemic preconditioning stimulates sodium and proton transport in isolated rat hearts

R. Ramasamy, Hong Liu, S. Anderson, J. Lundmark, Saul Schaefer

Research output: Contribution to journalArticle

75 Citations (Scopus)

Abstract

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 (Na(i)) 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 Na(i) by 6.24 ± 2.04 U, resulting in a significantly higher level of Na(i) before ischemia than in the control hearts. Na(i) 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 Na(i) accumulation during ischemia, but the decline in Na(i) 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 Na(i) 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, ΔpH = 0.35 ± 0.04 U over 5 min; control, ΔpH = 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 Na(i) 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.

Original languageEnglish (US)
Pages (from-to)1464-1472
Number of pages9
JournalJournal of Clinical Investigation
Volume96
Issue number3
StatePublished - 1995

Fingerprint

Ischemic Preconditioning
Protons
Sodium
Ischemia
Sodium-Hydrogen Antiporter
Reperfusion
Bumetanide
Creatine Kinase
Acidosis
Magnetic Resonance Spectroscopy
Acids

Keywords

  • ischemia
  • magnetic resonance spectroscopy
  • Na-K-2Cl cotransporter
  • NaH exchanger
  • preconditioning

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Ischemic preconditioning stimulates sodium and proton transport in isolated rat hearts. / Ramasamy, R.; Liu, Hong; Anderson, S.; Lundmark, J.; Schaefer, Saul.

In: Journal of Clinical Investigation, Vol. 96, No. 3, 1995, p. 1464-1472.

Research output: Contribution to journalArticle

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abstract = "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 (Na(i)) 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 Na(i) by 6.24 ± 2.04 U, resulting in a significantly higher level of Na(i) before ischemia than in the control hearts. Na(i) 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 Na(i) accumulation during ischemia, but the decline in Na(i) 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 Na(i) 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, ΔpH = 0.35 ± 0.04 U over 5 min; control, ΔpH = 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 Na(i) 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.",
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T1 - Ischemic preconditioning stimulates sodium and proton transport in isolated rat hearts

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AU - Liu, Hong

AU - Anderson, S.

AU - Lundmark, J.

AU - Schaefer, Saul

PY - 1995

Y1 - 1995

N2 - 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 (Na(i)) 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 Na(i) by 6.24 ± 2.04 U, resulting in a significantly higher level of Na(i) before ischemia than in the control hearts. Na(i) 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 Na(i) accumulation during ischemia, but the decline in Na(i) 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 Na(i) 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, ΔpH = 0.35 ± 0.04 U over 5 min; control, ΔpH = 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 Na(i) 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.

AB - 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 (Na(i)) 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 Na(i) by 6.24 ± 2.04 U, resulting in a significantly higher level of Na(i) before ischemia than in the control hearts. Na(i) 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 Na(i) accumulation during ischemia, but the decline in Na(i) 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 Na(i) 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, ΔpH = 0.35 ± 0.04 U over 5 min; control, ΔpH = 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 Na(i) 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.

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