Neutrophils pretreated with volatile anesthetics lose ability to cause cardiac dysfunction.
BACKGROUND
Volatile anesthetics can precondition the myocardium against functional depression and infarction following ischemia-reperfusion. Neutrophil activation, adherence, and release of superoxide play major roles in reperfusion injury. The authors tested the hypothesis that pretreatment of neutrophils with a volatile anesthetic, i.e., simulated preconditioning, can blunt their ability to cause cardiac dysfunction.


METHODS
Studies were performed in 60 buffer-perfused and paced isolated rat hearts. Left ventricular developed pressure served as an index of myocardial contractility. Polymorphonuclear neutrophils and/or drugs were added to coronary perfusate for 10 min, followed by 30 min of recovery. Platelet-activating factor was used to stimulate neutrophils. Pretreatment of neutrophils consisted of incubation with 1.0 minimum alveolar concentration (MAC) isoflurane or sevoflurane for 15 min, followed by washout. Additional studies were performed with 0.25 MAC isoflurane. Effects of superoxide dismutase were compared to those of volatile anesthetics. Superoxide production was measured by spectrophotometry. Neutrophil adherence to coronary vascular endothelium was estimated from the difference between neutrophils administered and recovered in coronary venous effluent.


RESULTS
Activated neutrophils caused marked, persistent reduction (> 50%) in left ventricular developed pressure. Isoflurane and sevoflurane at 1.0 MAC and superoxide dismutase abolished this effect. Isoflurane and sevoflurane reduced superoxide production of activated neutrophils by 29% and 33%, respectively, and completely prevented the platelet-activating factor-induced increases in neutrophil adherence. Isoflurane at 0.25 MAC blunted, but did not abolish, the neutrophil-induced decreases in left ventricular developed pressure.


CONCLUSIONS
Neutrophils pretreated with 1.0 MAC isoflurane or sevoflurane lost their ability to cause cardiac dysfunction, while those pretreated with a concentration of isoflurane as low as 0.25 MAC were partially inhibited. This action of the volatile anesthetics was associated with reductions in superoxide production and neutrophil adherence to the coronary vascular endothelium. Our findings suggest that inhibitory actions on neutrophil activation and neutrophil-endothelium interaction may contribute to the preconditioning effects of volatile anesthetics observed in vivo during myocardial ischemia-reperfusion.
Hu
Guochang
G
Advocate Illinois Masonic Medical Center, and Department of Anesthesiology, University of Illinois College of Medicine, Chicago 60657-5193, USA.
Vasiliauskas
Tomas
T
Salem
M Ramez
MR
Rhone
Douglas P
DP
Crystal
George J
GJ
D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D003326:Coronary Circulation; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology; D005260:Female; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods*; D007530:Isoflurane / Q000494:pharmacology; D008297:Male; D008738:Methyl Ethers / Q000494:pharmacology; D009200:Myocardial Contraction; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology; D010972:Platelet Activating Factor / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077149:Sevoflurane; D013481:Superoxides / Q000378:metabolism
D018685:Anesthetics, Inhalation; D008738:Methyl Ethers; D010972:Platelet Activating Factor; D013481:Superoxides; D000077149:Sevoflurane; D007530:Isoflurane