The effect of cyclosporin-A on peri-operative myocardial injury in adult patients undergoing coronary artery bypass graft surgery: a randomised controlled clinical trial.
OBJECTIVE
Cyclosporin-A (CsA) has been reported to reduce myocardial infarct size in both the experimental and clinical settings. This protective effect is dependent on its ability to prevent the opening of the mitochondrial permeability transition pore, a critical determinant of cell death in the setting of acute ischaemia-reperfusion injury. Whether CsA can reduce the extent of peri-operative myocardial injury (PMI) in patients undergoing coronary artery bypass graft (CABG) surgery is unknown, and is investigated in this randomised controlled clinical trial.


METHODS
78 adult patients undergoing elective CABG surgery were randomised to receive either an intravenous bolus of CsA (2.5 mg/kg) or placebo administered after induction of anaesthesia and prior to sternotomy. PMI was assessed by measuring serum cardiac enzymes, troponin T (cTnT) and CK-MB at 0, 6, 12, 24, 48 and 72 h after surgery.


RESULTS
There was no significant difference in mean peak cTnT levels between control (n=43) and CsA treatment (n=40) patients (0.56±0.06 ng/mL with control vs 0.35±0.05 ng/mL with CsA; p=0.07). However, in higher-risk patients with longer cardiopulmonary bypass times, there was a significant reduction in PMI with CsA therapy (p=0.049), with a reduced postoperative cTnT rise by 0.03 ng/mL for every 10 min, when compared with control.


CONCLUSIONS
In patients with longer cardiopulmonary bypass times, a single intravenous bolus of CsA administered prior to CABG surgery reduced the extent of PMI.
The Hatter Cardiovascular Institute, University College London, , London, UK.
Dj
Dj
Hausenloy
G
G
Kunst
E
E
Boston-Griffiths
S
S
Kolvekar
S
S
Chaubey
L
L
John
J
J
Desai
Dm
D
Yellon
D000368:Aged; D001026:Coronary Artery Bypass / Q000009:adverse effects*; D016572:Cyclosporine / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006331:Heart Diseases / Q000209:etiology* / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D011446:Prospective Studies
D007166:Immunosuppressive Agents; D016572:Cyclosporine
Cardiac Surgery; Myocardial Ischaemia and Infarction (IHD)