Efficient limitation of intracellular edema and sodium accumulation by cardioplegia is dissociated from recovery of rat hearts from cold ischemic storage

Nadir Askenasy, Antonio Vivi, Maria Tassini, Gil Navon

Research output: Contribution to journalArticlepeer-review

Abstract

Energy deficiency and disturbances of sodium and water homeostasis are considered as mechanisms of injury during hypothermic preservation of cardiac muscle. The present study attempts to characterize the effect of potassium (K+) and magnesium (Mg2+) cardioplegia on these mechanisms. Cellular parameters were measured by multinuclear NMR spectroscopy in isolated rat hearts during 12 h of ischemia at 4°C and 2 h of normothermic reperfusion with an isoosmotic Krebs-Henseleit (KH) solution. Potassium and magnesium cardioplegia (a) reduced the rate of ATP hydrolysis and cellular acidification during early stages of ischemia; (b) caused an early cessation of the phase of fast sodium influx after 40 min (P < 0.001 vs 120 min with KH); (c) reduced intracellular sodium accumulation to 148-165 μmol/gdw after 12 h (P < 0.01 vs 268 ± 15 μmol/gdw with KH), (d) decreased ischemic volumes to 2.7 ± 0.1 and 2.8 ± 0.1 ml/gdw after 8 and 12 h of storage, respectively (P < 0.005 v 3.0 and 3.3 ml/gdw with KH). Quantitative analysis of these parameters showed that both hypothermia and cardioplegia increased the relative contribution of sodium to intracellular water accumulation by a factor of 2-2.5. In view of the marked reduction in absolute sodium and water contents, the data indicate that cold cardioplegia limits the increase in intracellular osmolarity. Myocardial mechanical and metabolic recoveries, and cellular viability deteriorated during prolongation of the ischemic period from 8 to 12 h in all experimental groups (P < 0.005). Reperfusion was efficient in reversing intracellular sodium and water accumulation in hearts stored with cardioplegia, in contrast to hearts stored in KH. Magnesium, but not potassium cardioplegia, lowered interstitial water contents (P < 0.01 v KH), increased intracellular magnesium concentrations (P < 0.001), improved mechanical and metabolic recoveries (P < 0.01) and cellular viability (P < 0.001). These results indicate (a) cardioplegia reduces intracellular sodium (by ~ 46%) and water accumulation (by 66%) during cold ischemia; (b) both hypothermia and cardioplegia limit the rise in intracellular osmolarity and increase the contribution of sodium to cellular swelling; (c) intracellular sodium and water contents were dissociated from myocardial viability and recovery from cold ischemia in potassium and magnesium cardioplegic solutions. It is concluded that intracellular sodium and water accumulation are not dominant factors in determination of cardiac outcome from ischemia.

Original languageEnglish
Pages (from-to)1795-1808
Number of pages14
JournalJournal of Molecular and Cellular Cardiology
Volume31
Issue number10
DOIs
StatePublished - Oct 1999

Keywords

  • Cardiac presentation
  • Cellular volumes
  • Edema
  • Hypothermic ischemia
  • Magnesium cardioplegia
  • NMR spectroscopy
  • Potassium cardioplegia
  • Sodium ion

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