Attenuation of isoflurane-induced preconditioning and reactive oxygen species production in the senescent rat heart.
BACKGROUND
Although attenuation of anesthetic preconditioning in aged ex vivo heart models has been studied extensively, there are no comparable in vivo studies. To extend previous work and to address a possible mechanism underlying age-related differences, we investigated isoflurane-induced preconditioning and reactive oxygen species (ROS) production in the aged rat heart in vivo.


METHODS
Male Fisher 344 rats were assigned from their respective age groups (young, 3-5 mo; old, 20-24 mo) to either receive 30 min of 1.0 minimum alveolar concentration isoflurane or to a control group. Rats were subjected to coronary artery occlusion for 30 min followed by 2 h of reperfusion. A fluorescent probe for superoxide anion production (dihydroethidium, 1 mg) was administered in the absence of the isoflurane or just before isoflurane exposure in four additional groups. Myocardial infarct size and superoxide anion production were assessed using triphenyltetrazolium staining and epifluorescence microscopy, respectively.


RESULTS
Isoflurane decreased myocardial infarct size of young rats (26.7% +/- 3.0%) compared with young controls (50.9% +/- 1.9%; P < 0.001), whereas isoflurane did not significantly affect myocardial infarct size of old rats (39.1% +/- 0.9%) compared with old controls (46.5% +/- 2.4%; P > 0.05). Isoflurane increased ROS levels in young rats (430.5 +/- 95.9 arbitrary units [AU]) compared with young controls (162.7 +/- 25.5 AU; P < 0.01). In contrast, no significant changes in ROS levels were observed in old animals (316.4 +/- 56.3 AU isoflurane versus 233.8 +/- 59.2 AU control).


CONCLUSIONS
Reduction in the cardioprotective effects of isoflurane and attenuation of isoflurane-stimulated ROS production were observed in the senescent myocardium in vivo.
Nguyen
Long T
LT
Department of Anesthesiology, Stony Brook University School of Medicine, HSC L4 060, Stony Brook, NY 11794, USA.
Rebecchi
Mario J
MJ
Moore
Leon C
LC
Glass
Peter S A
PS
Brink
Peter R
PR
Liu
Lixin
L
D000375:Aging; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D016922:Cellular Senescence; D006321:Heart / Q000187:drug effects*; D019157:Ischemic Preconditioning, Myocardial; D007530:Isoflurane / Q000494:pharmacology*; D008297:Male; D023421:Models, Animal; D008954:Models, Biological; D009206:Myocardium / Q000473:pathology*; D051381:Rats; D011916:Rats, Inbred F344; D017382:Reactive Oxygen Species; D013997:Time Factors
D018685:Anesthetics, Inhalation; D017382:Reactive Oxygen Species; D007530:Isoflurane