title: Mechanisms of a reduced cardiac output and the effects of milrinone and levosimendan in a model of infant cardiopulmonary bypass.
abstract: OBJECTIVE
  A low cardiac output state is an important cause of morbidity after pediatric cardiopulmonary bypass. The objectives of our study were to define the early precipitants of the reduced cardiac output and to investigate the effects on these of milrinone and levosimendan in a model of pediatric cardiopulmonary bypass.
  
  
  METHODS
  Experimental study.
  
  
  METHODS
  : Research laboratory at a university-affiliated, tertiary pediatric center.
  
  
  METHODS
  Eighteen piglets.
  
  
  METHODS
  Piglets, instrumented with systemic, pulmonary arterial, and coronary sinus catheters, pulmonary and circumflex arterial flow probes, and a left ventricular conductance-micromanometer-tipped catheter, underwent cardiopulmonary bypass with aortic cross-clamp and cardioplegic arrest. At 120 mins, they were assigned to control, milrinone, or levosimendan groups and studied for a further 120 mins.
  
  
  RESULTS
  In controls, between 120 and 240 mins, cardiac output decreased by 15%. Systemic vascular resistance was unchanged, but pulmonary vascular resistance increased by 19%. Systemic arterial elastance increased by 17%, indicating increased afterload. End-systolic elastance was unchanged, and coronary sinus oxygen tension decreased by 4.0 +/- 1.7 mm Hg. In animals receiving milrinone cardiac output was preserved, and in animals receiving levosimendan cardiac output increased by 14%. Both drugs prevented an increase in arterial elastance and pulmonary vascular resistance after cardiopulmonary bypass. Systemic vascular resistance decreased by 31% after levosimendan, and end-systolic elastance increased by 48%, indicating improved contractility. Both agents prevented a decrease in coronary sinus oxygen tension.
  
  
  CONCLUSIONS
  Increased afterload, which is not matched by an equivalent elevation in contractility, contributes to the reduced cardiac output early after pediatric cardiopulmonary bypass in this model. This increase is prevented by milrinone and levosimendan. Both agents exert additional beneficial effects on pulmonary vascular resistance and myocardial oxygen balance, although levosimendan has greater inotropic properties.
authors.affiliation: Departments of Intensive Care, The Royal Children's Hospital, Melbourne, Australia.
authors.forename: Christian F
authors.initials: CF
authors.lastname: Stocker
authors.forename: Lara S
authors.initials: LS
authors.lastname: Shekerdemian
authors.forename: Martin A
authors.initials: MA
authors.lastname: Nørgaard
authors.forename: Christan P
authors.initials: CP
authors.lastname: Brizard
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Mynard
authors.forename: Steven B
authors.initials: SB
authors.lastname: Horton
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Penny
mesh_terms: D000367:Age Factors; D000818:Animals; D002302:Cardiac Output / Q000187:drug effects; D002303:Cardiac Output, Low / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D002316:Cardiotonic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D003971:Diastole / Q000187:drug effects; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006835:Hydrazones / Q000494:pharmacology / Q000627:therapeutic use*; D007223:Infant; D020105:Milrinone / Q000494:pharmacology / Q000627:therapeutic use*; D010101:Oxygen Consumption / Q000187:drug effects; D011659:Pulmonary Gas Exchange / Q000187:drug effects; D011724:Pyridazines / Q000494:pharmacology / Q000627:therapeutic use*; D012307:Risk Factors; D000077464:Simendan; D013552:Swine; D013997:Time Factors; D014655:Vascular Resistance / Q000187:drug effects; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D002316:Cardiotonic Agents; D006835:Hydrazones; D011724:Pyridazines; D000077464:Simendan; D020105:Milrinone