Anesthetic-induced preconditioning: previous administration of isoflurane decreases myocardial infarct size in rabbits.
BACKGROUND
Experimental evidence suggests that ATP-sensitive potassium channels are involved in myocardial ischemic preconditioning. Because some pharmacologic effects of isoflurane are mediated by K(ATP) channels, the authors tested the hypothesis: Isoflurane administration, before myocardial ischemia, can induce or mimic myocardial preconditioning.


METHODS
Myocardial infarct size was measured in three groups of propofol-anesthetized rabbits, each subjected to 30 min of anterolateral coronary occlusion followed by 3 h of reperfusion. Groups differed in their pretreatment: Group 1 (control, N = 13) no pretreatment, Group 2 (ischemic preconditioning, N = 8), 5 min of coronary occlusion and 15 min of reperfusion; Group 3 (isoflurane pretreatment; N = 15), 15 min of isoflurane (1.1% end-tidal) and 15 min of washout. Hemodynamics were monitored serially. Myocardial infarct size and the area at risk were defined using triphenyltetrazolium chloride staining and fluorescent microspheres, respectively, and both were measured using computerized planimetry.


RESULTS
Infarct size expressed as a percentage of area at risk was 23.4 +/- 8.5% (mean +/- SD) in the isoflurane group compared with 33.1 +/- 13.3% in controls, and 8.7 +/- 6.2% in the ischemia-preconditioned group. Analysis for coincidental regressions, followed by tests for equality of slope and elevation, showed that the linear relationship between infarct size and area at risk was significantly (P < 0.05) different in all three groups because of differences in line elevation. Minor differences in hemodynamic variables were found between groups, which were unlikely to account for the significant differences in infarct size.


CONCLUSIONS
Preadministration of isoflurane, before myocardial ischemia, reduces myocardial infarct size, and mimics myocardial preconditioning.
Cason
B A
BA
University of California, San Francisco, Department of Anesthesia, Veterans Affairs Medical Center, 94121, USA. Brian__Cason@quickmail.ucsf.edu
Gamperl
A K
AK
Slocum
R E
RE
Hickey
R F
RF
D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D006439:Hemodynamics / Q000187:drug effects*; D019157:Ischemic Preconditioning, Myocardial; D007530:Isoflurane / Q000494:pharmacology*; D009203:Myocardial Infarction / Q000517:prevention & control*; D011817:Rabbits; D014693:Ventricular Fibrillation / Q000517:prevention & control
D018685:Anesthetics, Inhalation; D007530:Isoflurane