title: Carvedilol-Enriched Cold Oxygenated Blood Cardioplegia Improves Left Ventricular Diastolic Function After Weaning From Cardiopulmonary Bypass.
abstract: OBJECTIVE
  To investigate whether adding carvedilol, a nonselective β- and selective α1-receptor blocking agent with antioxidant properties, to oxygenated blood cardioplegia improves myocardial function after weaning from bypass.
  
  
  METHODS
  A randomized controlled study.
  
  
  METHODS
  A university laboratory.
  
  
  METHODS
  Twenty anesthetized pigs, Norwegian Landrace.
  
  
  METHODS
  On cardiopulmonary bypass, cardiac arrest was induced with cold (12°C), oxygenated blood cardioplegia, enriched with carvedilol or vehicle, and repeated every 20 minutes. After 100 minutes, the heart was reperfused and weaned.
  
  
  RESULTS
  Left ventricular function was evaluated with pressure-volume loops, local myocardial systolic strain, and strain rate from Speckle tracking analysis and multilayer short-axis tissue Doppler Imaging. In the carvedilol group, the load-independent logarithmic end-diastolic pressure volume relationship, β, decreased from 1 to 3 hours of reperfusion and was low, 0.028±0.004 v 0.042±0.007 (p<0.05) in controls at 3 hours, demonstrating improved left ventricular compliance. The diastolic relaxation constant τ was decreased, 28.9±0.6 ms v 34.6±1.3 ms (pg<0.035), and dP/dtmin was more negative,-1,462±145 mmHg/s v-1,105±105 mmHg/s (pg = 0.024), for carvedilol v control group. The systolic variables, preload recruitable stroke work and end-systolic pressure-volume relationship, did not differ between groups, neither did left ventricular systolic strain and strain rate. Myocardial oxidative stress, measured as tissue levels of malondialdehyde, was reduced by carvedilol, 0.19±0.01 compared to 0.24±0.01 nmol/mg (p = 0.004) in controls.
  
  
  CONCLUSIONS
  Carvedilol added to blood cardioplegia improved diastolic cardiac function and reduced oxidative stress during the first 3 hours after reperfusion in a porcine model, with 100 minutes of cardioplegic arrest.
authors: Section of Cardiothoracic Surgery, Department of Heart Disease, Haukeland University Hospital, Bergen, Norway;; Department of Clinical Science, University of Bergen, Bergen, Norway;. Electronic address: geir.olav.dahle@helse-bergen.no.
authors: Geir Olav
authors: GO
authors: Dahle
authors: Section of Cardiothoracic Surgery, Department of Heart Disease, Haukeland University Hospital, Bergen, Norway;; Department of Clinical Science, University of Bergen, Bergen, Norway;
authors: Pirjo-Riitta
authors: PR
authors: Salminen
authors: Department of Clinical Science, University of Bergen, Bergen, Norway;
authors: Christian Arvei
authors: CA
authors: Moen
authors: Section of Cardiothoracic Surgery, Department of Heart Disease, Haukeland University Hospital, Bergen, Norway;
authors: Finn
authors: F
authors: Eliassen
authors: Section of Cardiothoracic Surgery, Department of Heart Disease, Haukeland University Hospital, Bergen, Norway;
authors: Else
authors: E
authors: Nygreen
authors: Heart Center, Turku University Hospital, University of Turku, Turku, Finland;; Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland.
authors: Ville
authors: V
authors: Kytö
authors: Department of Pathology and Forensic Medicine, University of Turku, Turku, Finland.
authors: Pekka
authors: P
authors: Saukko
authors: Section of Cardiothoracic Surgery, Department of Heart Disease, Haukeland University Hospital, Bergen, Norway;; Department of Clinical Science, University of Bergen, Bergen, Norway;
authors: Rune
authors: R
authors: Haaverstad
authors: Department of Clinical Science, University of Bergen, Bergen, Norway;
authors: Knut
authors: K
authors: Matre
authors: Department of Clinical Science, University of Bergen, Bergen, Norway;
authors: Ketil
authors: K
authors: Grong
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D002227:Carbazoles / Q000008:administration & dosage / Q000494:pharmacology*; D002315:Cardiopulmonary Bypass / Q000009:adverse effects / Q000379:methods*; D000077261:Carvedilol; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006324:Heart Arrest, Induced / Q000009:adverse effects / Q000379:methods*; D015425:Myocardial Reperfusion; D018384:Oxidative Stress / Q000187:drug effects; D010100:Oxygen / Q000097:blood; D011412:Propanolamines / Q000008:administration & dosage / Q000494:pharmacology*; D011897:Random Allocation; D034421:Sus scrofa; D018487:Ventricular Dysfunction, Left / Q000209:etiology / Q000517:prevention & control; D016277:Ventricular Function, Left / Q000187:drug effects* / Q000502:physiology
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol; D010100:Oxygen
keywords: cardiac function; cardioplegia; cardiopulmonary bypass; carvedilol; oxidative stress