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Ann Thorac Surg 2003;76:1240-1245
© 2003 The Society of Thoracic Surgeons

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Original article: cardiovascular

Protection of myocardium by cyclosporin A and insulin: in vitro simulated ischemia study in human myocardium

^a Joseph Lunenfeld Cardiac Surgery Research Center, Hadassah University Hospital, Jerusalem, Israel
^b Cardiothoracic Surgery Department, Hadassah University Hospital, Jerusalem, Israel

Accepted for publication April 8, 2003.

^* Address reprint requests to Dr Schwalb, Joseph Lunenfeld Cardiac Surgery Research Center, Hadassah University Hospital, PO Box 12000, 91120 Jerusalem, Israel.
e-mail: schwalb{at}hadassah.org.il

BACKGROUND: The efficacy of myocardial protection by cyclosporin A (CSA) and insulin was tested in human right atrial myocardial slices subjected to simulated ischemia and reoxygenation.

METHODS: Slices of right atrial trabeculae were obtained from patients undergoing elective cardiac surgery. Trabeculae were incubated with oxygenated glucose containing phosphate buffered saline (O₂, G-PBS). After 30 minutes of stabilization the sections were exposed to 90 minutes of simulated ischemia (N₂, PBS without glucose) followed by 90 minutes reoxygenation (O₂, G-PBS). Cyclosporin A (0.2 µmol/L) or insulin (5 mU/mL) was added during the stabilization period prior the ischemia. Cell viability was measured by using 3-[4.5 dimethylthiazol 2-yl]-2,5-diphenyltetrazolium bromide (MTT), which is cleaved by active mitochondrial dehydrogenases of living cells.

RESULTS: The viability of untreated slices (control) was 30.45% ± 2.5% versus 52.65% ± 4.4% in the CSA treated slices, p less than 0.001. The extent of protection by CSA was affected by oral antiglycemic drugs (glibenclamide). The effect obtained by CSA was inhibited by 5-hydroxydecanoate (5HD), a specific blocker of mitochondrial K_ATP channels. Protection of the myocardial slices with insulin appears to be superior and not affected by the medication before surgery. This protection was maximal when insulin was present during both preischemic equilibration and reoxygenation periods (68.9% ± 9.3% viability with insulin versus 33.2% ± 6.9% in the control, p < 0.001).

CONCLUSIONS: Protection of right atrial trabeculae slices with insulin is superior to that obtained with CSA and is independent of preoperative medication.

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