Bradykinin preconditioning in coronary artery bypass grafting.
BACKGROUND
Experimental studies have shown that activation of bradykinin B2 receptor is one of the most important triggers of ischemic preconditioning. However, the effect of exogenous administration of bradykinin in cardiac surgery is not yet known. The present prospective randomized study was designed to investigate the effect of bradykinin pretreatment in patients undergoing elective coronary artery bypass surgery.


METHODS
Forty-one patients with multiple-vessel coronary artery disease and stable angina, admitted for the first time for elective coronary artery bypass surgery, were randomized into control or bradykinin (BK) groups. Patients in the BK group received bradykinin infusion for 7 minutes (total dose 25 microg) before the initiation of cardiopulmonary bypass. Perioperative cardiac specific troponin I (cTnI) and creatine kinase cardiac isoenzyme (CKMB) release and hemodynamics were recorded.


RESULTS
Bradykinin infusion caused acute decrease of blood pressure in most of the cases and the mean minimum mean blood pressure during bradykinin infusion was 72.7% of the original mean blood pressure (MBP) level (74.7 +/- 7.9 vs 54.4 +/- 12.1 mm Hg, p < 0.01). There were no differences in baseline levels of cTnI and CKMB between the groups. The postoperative cTnI levels were lower than 10 ng/mL in most patients in both groups (18 in the BK group and 15 in the control group). There was no difference in cTnI between the groups. However, patients who received bradykinin released significantly less CKMB than did the controls postoperatively (6 hours, BK, 22.1 +/- 9.5 vs control, 23.6 +/- 12.7 U/L; 12 hours, BK, 19.4 +/- 12.4 vs control, 28.7 +/- 23.8 U/L; 24 hours, BK, 21.5 +/- 14.7 vs control, 35.5 +/- 28.9 U/L; 48 hours, BK, 14.4 +/- 7.5 vs control, 23.5 +/- 13.6 U/L; analysis of variance [ANOVA] for repeated measurement, p = 0.036). Maximum CKMB was also lower in the BK group (22.4 +/- 14.4 vs 37.7 +/- 27.5 U/L, p = 0.044). There was no significant difference between the groups in any of the hemodynamic variables.


CONCLUSIONS
Exogenous bradykinin infusion showed weak cardioprotective effect in the low-risk patients undergoing coronary artery bypass surgery but the dose used in the study caused acute decrease of systemic blood pressure.
Division of Cardiothoracic Surgery, Tampere University Hospital, FIN-33521 Tampere, Finland.
Minxin
M
Wei
Xin
X
Wang
Pekka
P
Kuukasjärvi
Jari
J
Laurikka
Timo
T
Rinne
Eva-Liisa
EL
Honkonen
Matti
M
Tarkka
D000368:Aged; D000787:Angina Pectoris / Q000097:blood / Q000601:surgery*; D015415:Biomarkers; D001920:Bradykinin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001026:Coronary Artery Bypass; D003402:Creatine Kinase / Q000097:blood; D052279:Creatine Kinase, MB Form; D017558:Elective Surgical Procedures; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007022:Hypotension / Q000139:chemically induced; D007262:Infusions, Intravenous; D007431:Intraoperative Complications / Q000139:chemically induced; D019194:Ischemic Preconditioning / Q000379:methods*; D007527:Isoenzymes / Q000097:blood; D008297:Male; D008875:Middle Aged; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control; D011229:Preanesthetic Medication; D011446:Prospective Studies; D016896:Treatment Outcome; D019210:Troponin I / Q000097:blood
D015415:Biomarkers; D002316:Cardiotonic Agents; D007527:Isoenzymes; D019210:Troponin I; D003402:Creatine Kinase; D052279:Creatine Kinase, MB Form; D001920:Bradykinin