title: Metabolic changes induced by ischemia and cardioplegia: a study employing cardiac microdialysis in pigs.
abstract: OBJECTIVE
  The present study investigates dynamic changes of myocardial metabolism in response to ischemia, cardioplegia, and extracorporeal circulation (ECC) in order to differentiate between the contributing effects of each of these interventions. Furthermore, warm blood cardioplegia versus empty beating of the heart were compared as methods to resuscitate the ischemic myocardial metabolism.
  
  
  METHODS
  Swedish Landrace pigs on ECC (ECC) were compared with pigs on ECC with warm ischemic cardiac arrest (ischemia) or on ECC with warm ischemic arrest followed by warm blood cardioplegia (ischemia-cardioplegia), using sham-operated pigs as controls (n=7 in each group). Microdialysis probes were placed on the surface of the left ventricle and in the femoral artery for serial evaluation of metabolites in the intracardiac extracellular fluid and arterial blood. When hearts started in ventricular fibrillation (VF), it was electroconverted after 10 min of normal blood reperfusion. If VF started after 10 min of reperfusion electroconversion was immediately performed.
  
  
  RESULTS
  There were no differences between groups in arterial contents of serine, citrulline, arginine, inosine, hypoxanthine, guanosine, aspartate, glutamate, pyruvate, or asparagine throughout the observation period. Systemic lactate increased in pigs subjected to ischemia (P<0.001) or ischemia and cardioplegia (P=0.002), highest in the ischemia only group (P=0.002). In left ventricular microdialysates, lactate increased in pigs subjected to ischemia alone (P<0.001 vs. ECC) and ischemia and cardioplegia (P=0.004 vs. ECC). Guanosine increased in ischemia versus ECC (P=0.002), while hypoxanthine was increased in microdialysates of both ischemic (P=0.002) and ischemic-cardioplegic (P=0.001) pig hearts. Inosine was increased in pigs subjected to ischemia and cardioplegia (P<0.001 vs. ECC). All ischemic hearts started with VF, but while in the warm ischemia group VF started within 10 min of reperfusion, the ischemia-cardioplegia group had a longer asystolia with VF starting 11-22 min of blood reperfusion.
  
  
  CONCLUSIONS
  The heart should be allowed to start empty beating rather than by the use of warm continuous blood cardioplegia. Microdialysis and sampling of interstitial metabolites may be advantageous when an increased sensitivity is needed or when repeated blood sampling is difficult or contraindicated in monitoring of the myocardium.
authors.affiliation: Crafoord Laboratory of Experimental Surgery, Karolinska Institute, Stockholm, Sweden. guro.valen@cmm.ki.se
authors.forename: Guro
authors.initials: G
authors.lastname: Valen
authors.forename: Anders
authors.initials: A
authors.lastname: Owall
authors.forename: Shigeto
authors.initials: S
authors.lastname: Takeshima
authors.forename: Michel
authors.initials: M
authors.lastname: Goiny
authors.forename: Urban
authors.initials: U
authors.lastname: Ungerstedt
authors.forename: Jarle
authors.initials: J
authors.lastname: Vaage
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001158:Arteries / Q000378:metabolism; D002956:Citrulline / Q000378:metabolism; D005112:Extracorporeal Circulation / Q000379:methods; D005260:Female; D006151:Guanosine / Q000378:metabolism; D006324:Heart Arrest, Induced; D006352:Heart Ventricles / Q000378:metabolism; D019271:Hypoxanthine / Q000378:metabolism; D007288:Inosine / Q000378:metabolism; D007773:Lactates / Q000378:metabolism; D008297:Male; D017551:Microdialysis; D017202:Myocardial Ischemia / Q000378:metabolism*; D013552:Swine
chemical_list: D007773:Lactates; D006151:Guanosine; D002956:Citrulline; D019271:Hypoxanthine; D007288:Inosine