Halothane prevents postischemic production of hydroxyl radicals in the canine heart.
BACKGROUND
Recent studies indicate that during regional myocardial ischemia and subsequent reperfusion, volatile anesthetics may provide protection against free radical-related injury. The effect of halothane on free radical production during ischemia and reperfusion, in the canine heart, was investigated. The level of hydroxyl radical (.OH)-mediated conversion of salicylate to its dehydroxybenzoate derivatives (2,3-DHBA and 2,5-DHBA) was monitored.


METHODS
Under general anesthesia, the heart was exposed through median sternotomy. Salicylate (100 mg/kg given intravenously) was administered 30 min before left anterior descending artery occlusion. Six dogs were studied using inhaled halothane (1.6%) 10 min before and during the 10-min ischemic period, followed by 50 min of reperfusion, and then they were compared with seven other dogs used as controls. Blood concentrations of salicylate, 2,3-DHBA and 2,5-DHBA, K+, lactate, oxygen content, and pH were monitored.


RESULTS
An acute increase in the normalized concentrations of 2,3-DHBA and 2,5-DHBA was observed in the control animals during reperfusion. In contrast, halothane inhalation completely inhibited the production of both metabolites (P < 0.02), but 2,5-DHBA concentrations in the halothane-treated group were even less than the basal level (P < 0.05). The increase in lactate concentrations in the experimental animals was significantly less than that of controls (P < 0.05) and followed the same time-dependent pattern as the changes in K+ and pH. Halothane significantly decreased (P < 0.0001) the difference in oxygen content between coronary sinus and aortic root blood, suggesting decreased oxygen utilization during reperfusion.


CONCLUSIONS
Halothane completely inhibited the production of .OH, and its administration may protect the heart from the deleterious effect of oxygen-derived reactive species, with attenuation of the metabolic response to ischemia.
Glantz
L
L
Department of Anesthesiology and Critical Care Medicine, Hadassah University Hospital, Jerusalem, Israel.
Ginosar
Y
Y
Chevion
M
M
Gozal
Y
Y
Elami
A
A
Navot
N
N
Kitrossky
N
N
Drenger
B
B
D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D004285:Dogs; D005841:Gentisates; D006221:Halothane / Q000494:pharmacology*; D062385:Hydroxybenzoates / Q000032:analysis; D017665:Hydroxyl Radical / Q000378:metabolism*; D017202:Myocardial Ischemia / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*
D018685:Anesthetics, Inhalation; D005841:Gentisates; D062385:Hydroxybenzoates; D017665:Hydroxyl Radical; C009135:2,3-dihydroxybenzoic acid; D006221:Halothane; C010925:2,5-dihydroxybenzoic acid