Effect of sodium bicarbonate infusion on hepatocyte Ca2+ overload during resuscitation from hemorrhagic shock.
Ischemia/reperfusion events alter the cellular ion homeostasis by intracellular acidosis and a subsequent rise of sodium and calcium concentrations. Since disturbance of intracellular Ca2+ signaling pathways impairs cellular function, we investigated the effect of sodium bicarbonate infusion on hepatocellular Ca2+ dysregulation induced by resuscitation from hemorrhagic shock. Anesthetized Sprague-Dawley rats were bled to a mean arterial blood pressure of 40 mmHg for 60 min. Rats were resuscitated by retransfusion of shed blood (60%) in 20 min and three-fold the bleed out volume as lactated Ringers' during 60 min and received either a bolus infusion of sodium bicarbonate (2 mval/kg body weight) or an equal volume of sodium chloride (0.9%). After hepatocyte isolation by portal collagenase perfusion, the rate of Ca2+ influx (Ca2+in) in the absence and presence of epinephrine (100 nM), cellular Ca2+ uptake (Ca2+up) and membrane Ca2+ flux (Ca2+flux) were determined using 45Ca2+ incubation techniques. Hemorrhage/resuscitation substantially increased hepatocyte Ca2+up (3.44 +/- 0.2 nmol/mg protein) and Ca2+flux (32.8 +/- 5 pmol/mg protein x min) compared to sham-operated controls (2.57 +/- 0.1 and 15.2 +/- 3.5; P < 0.05). Resuscitation with sodium bicarbonate significantly prevented altered hepatocyte Ca2+ regulation (2.31 +/- 0.1 and 14.4 +/- 4.6; P < 0.05). These findings suggested that postischemic hepatocyte Ca2+ overload could partly be due to enhanced membrane Ca2+ movements to correct for altered intracellular pH homeostasis.
Department of Anesthesiology and Critical Care Medicine, University of Saarland, Homburg/Saar, Germany.
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Silomon
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Rose
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D016887:Cardiopulmonary Resuscitation; D002462:Cell Membrane / Q000378:metabolism; D006439:Hemodynamics / Q000502:physiology; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012771:Shock, Hemorrhagic / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*; D017693:Sodium Bicarbonate / Q000494:pharmacology*
D017693:Sodium Bicarbonate; D002118:Calcium