Flumazenil mimics whereas midazolam abolishes ischemic preconditioning in a rabbit heart model of ischemia-reperfusion.
Anesthesiology
; 105(1): 65-71, 2006 Jul.
Article
em En
| MEDLINE
| ID: mdl-16809996
ABSTRACT
BACKGROUND:
The goal of the current study was to assess the effects of flumazenil, a benzodiazepine receptor antagonist, in limiting infarct size and in reducing hydroxyl free radical production.METHODS:
After intravenous salicylate (100 mg/kg) administration, rabbits were subjected to 40 min of regional myocardial ischemia and 2 h of reperfusion. In one group, flumazenil (0.05 mg/kg) and, in another, midazolam (0.05 mg/kg) was administered 15 min before 40 min of ischemia. Ischemic preconditioning (IP) was elicited by 5 min of ischemia followed by 10 min of reperfusion (before the 40-min ischemia period). In two other groups, midazolam was added to flumazenil and IP. Infarct size was determined using triphenyl tetrazolium chloride staining. The authors quantified the hydroxyl-mediated conversion of salicylate to its 2,3- and 2,5-dihydroxybenzoate derivatives during reperfusion by high-performance liquid chromatography coupled with electrochemical detection. Results are expressed as mean +/- SEM.RESULTS:
Flumazenil, like IP, significantly decreased infarct size (23 +/- 4 and 22 +/- 5%, respectively, vs. 57 +/- 6% in control group; P < 0.01). Midazolam inhibited the effects of flumazenil and IP. Flumazenil and IP significantly limited the increase in the normalized concentrations of 2,3- and 2,5-dihydroxybenzoic acids. With midazolam, however, the increase was comparable to that of the control group. 5-Hydroxydecanoate, a selective mitochondrial adenosine triphosphate-sensitive K channel blocker, given with flumazenil, abolished the protection obtained with the latter.CONCLUSIONS:
Flumazenil mimics preconditioning to decrease infarct size and hydroxyl radical production during reperfusion. Midazolam, however, abolishes these effects. Blockade of benzodiazepine receptors is upstream to the mitochondrial adenosine triphosphate-sensitive K channels in the preconditioning cascade.
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Base de dados:
MEDLINE
Assunto principal:
Midazolam
/
Traumatismo por Reperfusão Miocárdica
/
Flumazenil
/
Precondicionamento Isquêmico Miocárdico
Idioma:
En
Ano de publicação:
2006
Tipo de documento:
Article