Protection of myocardium by cyclosporin A and insulin: in vitro simulated ischemia study in human myocardium.
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 (O(2), G-PBS). After 30 minutes of stabilization the sections were exposed to 90 minutes of simulated ischemia (N(2), PBS without glucose) followed by 90 minutes reoxygenation (O(2), G-PBS). Cyclosporin A (0.2 micromol/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.
Schneider
Aviva
A
Joseph Lunenfeld Cardiac Surgery Research Center, and Cardiothoracic Sugery Department, Hadassah University Hospital, Jerusalem, Israel.
Ad
Niv
N
Izhar
Uzi
U
Khaliulin
Igor
I
Borman
Joseph B
JB
Schwalb
Herzl
H
D002470:Cell Survival / Q000187:drug effects; D016572:Cyclosporine / Q000494:pharmacology*; D003652:Decanoic Acids / Q000494:pharmacology; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D006325:Heart Atria / Q000187:drug effects*; D006801:Humans; D006880:Hydroxy Acids / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000494:pharmacology; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D015425:Myocardial Reperfusion
D003652:Decanoic Acids; D006880:Hydroxy Acids; D007004:Hypoglycemic Agents; D007328:Insulin; C052853:5-hydroxydecanoic acid; D016572:Cyclosporine; D005905:Glyburide