Isoflurane preconditions myocardium against infarction via release of free radicals.
BACKGROUND
Isoflurane exerts cardioprotective effects that mimic the ischemic preconditioning phenomenon. Generation of free radicals is implicated in ischemic preconditioning. The authors investigated whether isoflurane-induced preconditioning may involve release of free radicals.


METHODS
Sixty-one alpha-chloralose-anesthetized rabbits were instrumented for measurement of left ventricular (LV) pressure (tip-manometer), cardiac output (ultrasonic flowprobe), and myocardial infarct size (triphenyltetrazolium staining). All rabbits were subjected to 30 min of occlusion of a major coronary artery and 2 h of subsequent reperfusion. Rabbits of all six groups underwent a treatment period consisting of either no intervention for 35 min (control group, n = 11) or 15 min of isoflurane inhalation (1 minimum alveolar concentration end-tidal concentration) followed by a 10-min washout period (isoflurane group, n = 12). Four additional groups received the radical scavenger N-(2-mercaptoproprionyl)glycine (MPG; 1 mg. kg-1.min-1) or Mn(III)tetrakis(4-benzoic acid)porphyrine chloride (MnTBAP; 100 microg.kg-1.min-1) during the treatment period with (isoflurane + MPG; n = 11; isoflurane + MnTBAP, n = 9) or without isoflurane inhalation (MPG, n = 11; MnTBAP, n = 7).


RESULTS
Hemodynamic baseline values were not significantly different between groups (LV pressure, 97 +/- 17 mmHg [mean +/- SD]; cardiac output, 228 +/- 61 ml/min). During coronary artery occlusion, LV pressure was reduced to 91 +/- 17% of baseline and cardiac output to 94 +/- 21%. After 2 h of reperfusion, recovery of LV pressure and cardiac output was not significantly different between groups (LV pressure, 83 +/- 20%; cardiac output, 86 +/- 23% of baseline). Infarct size was reduced from 49 +/- 17% of the area at risk in controls to 29 +/- 19% in the isoflurane group (P = 0.04). MPG and MnTBAP themselves had no effect on infarct size (MPG, 50 +/- 14%; MnTBAP, 56 +/- 15%), but both abolished the preconditioning effect of isoflurane (isoflurane + MPG, 50 +/- 24%, P = 0.02; isoflurane + MnTBAP, 55 +/- 10%, P = 0.001).


CONCLUSIONS
Isoflurane-induced preconditioning depends on the release of free radicals.
Müllenheim
Jost
J
Klinik für Anaesthesiologie and Institut für Herz- und Kreislaufphysiologie, Heinrich Heine Universität Düsseldorf, Düsseldorf, Germany.
Ebel
Dirk
D
Frässdorf
Jan
J
Preckel
Benedikt
B
Thämer
Volker
V
Schlack
Wolfgang
W
D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D005609:Free Radicals; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects; D019157:Ischemic Preconditioning, Myocardial; D007530:Isoflurane / Q000494:pharmacology*; D008665:Metalloporphyrins / Q000494:pharmacology; D009203:Myocardial Infarction / Q000517:prevention & control*; D011817:Rabbits; D013438:Sulfhydryl Compounds / Q000494:pharmacology
D018685:Anesthetics, Inhalation; D005609:Free Radicals; D008665:Metalloporphyrins; C110658:N-(2-mercaptoproprionyl)-glycine; D013438:Sulfhydryl Compounds; C097284:manganese(III)-tetrakis(4-benzoic acid)porphyrin; D007530:Isoflurane; D005998:Glycine