title: The myocardial protective effect of adenosine as an adjunct to intermittent blood cardioplegia during open heart surgery.
abstract: BACKGROUND
  Although adenosine (ADO) has been shown to have beneficial effects against tissue injury after myocardial ischaemia, the controversy still remains regarding the optimal timing, dose, temperature, method of ADO administration and duration of exposure to the drug. This study investigates the cardioprotective effect of exogenous ADO pretreatment as an adjunct to 1 mmol l(-1) ADO cold (12 degrees C) blood cardioplegia during heart valve replacement surgery.
  
  
  METHODS
  Thirty patients with rheumatic heart valve disease undergoing heart valve replacement operations were randomly assigned to two groups: group C (n=15) and group A (n=15). Patients in group C were the control group and received antegrade cold (12 degrees C) high-potassium ([K(+)]=20 mol l(-1)) institute blood cardioplegia. The patients in group A received 10-min 100 microgkg(-1)min(-1) ADO pretreatment before application of the aortic cross-clamp and antegrade 1 mmol l(-1) adenosine high-potassium ([K(+)]=20 mol l(-1)) cold (12 degrees C) blood cardioplegia. Clinical outcomes were observed before, during and after the operation. Plasma level markers of myocardial damage: cardiac Troponin I (cTnI), creatine kinase (CK-MB) and inflammatory factors (interleukin (IL)-6 and IL-8) were obtained from serial venous blood samples after induction, 5 min after cross-clamp of aorta, 10 min after clamp-off, 1h after return to ICU and postoperatively 24 h and 48 h. Right atrial samples were harvested before cross-clamp and after clamp-off.
  
  
  RESULTS
  Heart valve replacement was successful in all patients. There were no differences regarding operative parameters in the two groups. Time to arrest (during cardiolegia perfusion electrocardiography (ECG) change to a line) was shorter in group A compared to group C (19.9+/-4.6s vs 29.3+/-10.6s; p=0.03). Group A also had lower cTnI and IL-8 levels (p=0.03) at 10 min after aortic declamping, and lower IL-6 (p=0.04) at 24h postoperatively as well. Ultrastructural changes were slighter in group A than group C after clamp-off. Compared to group C, post-reperfusion biopsies in group A displayed only slight overall ultrastructural changes, and scored significantly better on mitochondrial damage (group A 2.23+/-0.65 vs group C 2.85+/-0.66) (p=0.04).
  
  
  CONCLUSIONS
  Compared with simple cold blood cardioplegia in heart valve replacement patients, ADO pretreatment as an adjunct to 1 mmol l(-1) ADO cold blood cardioplegia may reduce cTnI, IL-6 and IL-8 release, resulting in reduced myocardial injury in ultrastructure after surgery.
authors.affiliation: Department of Cardiopulmonary Bypass, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, PR China.
authors.forename: Ruifang
authors.initials: R
authors.lastname: Liu
authors.forename: Jialin
authors.initials: J
authors.lastname: Xing
authors.forename: Na
authors.initials: N
authors.lastname: Miao
authors.forename: Weiran
authors.initials: W
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Yong-Qiang
authors.initials: YQ
authors.lastname: Lai
authors.forename: Yi
authors.initials: Y
authors.lastname: Luo
authors.forename: Bingyang
authors.initials: B
authors.lastname: Ji
mesh_terms: D000241:Adenosine / Q000008:administration & dosage / Q000627:therapeutic use*; D000328:Adult; D015415:Biomarkers / Q000097:blood; D002315:Cardiopulmonary Bypass / Q000009:adverse effects; D052279:Creatine Kinase, MB Form / Q000097:blood; D004334:Drug Administration Schedule; D005260:Female; D006324:Heart Arrest, Induced / Q000379:methods*; D019918:Heart Valve Prosthesis Implantation / Q000009:adverse effects* / Q000379:methods; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D007430:Intraoperative Care / Q000379:methods; D008297:Male; D008875:Middle Aged; D008929:Mitochondria, Heart / Q000648:ultrastructure; D015428:Myocardial Reperfusion Injury / Q000209:etiology / Q000517:prevention & control*; D011446:Prospective Studies; D019210:Troponin I / Q000097:blood; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D015415:Biomarkers; D015850:Interleukin-6; D016209:Interleukin-8; D019210:Troponin I; D014665:Vasodilator Agents; D052279:Creatine Kinase, MB Form; D000241:Adenosine