title: Role of sodium pump activity in warm induction of cardioplegia combined with reperfusion of oxygenated cardioplegic solution.
abstract: Na+/K+ adenosinetriphosphatase (sodium pump) may play a key role in the prevention of reperfusion injury caused by Ca2+ overload. The present study was undertaken to investigate the role of sodium pump activity in warm induction of cardioplegia combined with reperfusion of oxygenated cardioplegic solution. Isolated and perfused rat hearts were subjected to 15 minutes of normothermic ischemia to produce a model of severely failing heart. The hearts then received myocardial preservation. Warm (37 degrees C) or cold (4 degrees C) oxygenated modified St. Thomas' Hospital solution was given for 5 minutes before and after 120 minutes of hypothermic cardioplegic arrest. Reduced myocardial pH during normothermic ischemia was adjusted toward the baseline level by administration of cold or warm oxygenated cardioplegic solution without a significant intergroup difference. Myocardial adenosine triphosphate levels decreased to less than 30% of the preischemic level during 15 minutes of normothermic ischemia, but were increased partly by induction of cold or warm oxygenated cardioplegia. Thus these metabolic indices failed to demonstrate the superiority of warm over cold oxygenated cardioplegia. Na+/K+ adenosinetriphosphatase activity in the membrane fraction was significantly stimulated by a cardioplegic dose of K+ with maximum activity at 16 mEq/L. The enzyme activity of the heart measured after normothermic ischemia was reduced to less than 50% of that in the nonischemic heart. Although warm induction of cardioplegia and reperfusion of oxygenated cardioplegic solution maintained Na+/K+ adenosinetriphosphatase activity at the preischemic level, the enzyme activity was abolished at 4 degrees C, which is the temperature used in cold cardioplegia. A subtoxic dose of ouabain (0.1 mmol/L) inhibited the enzyme activity of the heart undergoing this preservation regimen to approximately 50%. Warm induction and reperfusion of oxygenated cardioplegic solution showed significantly better recovery of isovolumic left ventricular function during reperfusion compared with that obtained with cold oxygenated cardioplegia. However, the beneficial effect of warm oxygenated cardioplegia on left ventricular function was compromised by inclusion of 0.1 mmol/L ouabain without a significant effect on myocardial metabolic parameters. These results suggest that stimulation of Na+ pump activity may account for the beneficial effect of warm induction and reperfusion of oxygenated cardioplegic solution in the energy-depleted heart.
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Kansai Medical University, Osaka, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Ko
authors.forename: H
authors.initials: H
authors.lastname: Otani
authors.forename: H
authors.initials: H
authors.lastname: Imamura
authors.forename: K
authors.initials: K
authors.lastname: Omori
authors.forename: C
authors.initials: C
authors.lastname: Inagaki
mesh_terms: D000136:Acid-Base Equilibrium; D000255:Adenosine Triphosphate / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D002314:Cardioplegic Solutions / Q000008:administration & dosage*; D066298:In Vitro Techniques; D008297:Male; D017202:Myocardial Ischemia / Q000378:metabolism; D010042:Ouabain / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015424:Reperfusion; D015427:Reperfusion Injury / Q000517:prevention & control*; D000254:Sodium-Potassium-Exchanging ATPase / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D013696:Temperature; D016277:Ventricular Function, Left / Q000187:drug effects / Q000502:physiology
chemical_list: D002314:Cardioplegic Solutions; D010042:Ouabain; D000255:Adenosine Triphosphate; D000254:Sodium-Potassium-Exchanging ATPase