The Effects of Volatile General Anesthetics on Adenosine Diphosphate-induced Platelet Aggregation

Ueda, Issaku

doi:10.1097/00000542-197105000-00006

Cited by 60 publications

(18 citation statements)

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“…While anesthetic drugs primarily act on neuronal cells in the central nervous system [1], thereby inducing general anesthetic states, the report that halothane impairs adenosine diphosphate (ADP)-induced platelet aggregation by Ueda [2] triggered subsequent studies on the effect of hemostasis. Clinical observational investigations into the effects of anesthetics on hemostasis during surgery [3], point to an intriguing trend that intra-operative bleedings were less severe in anesthesia with the intravenous anesthetic propofol than volatile anesthetics isoflurane and sevoflurane [3], [4], [5], [9], [10] ( Table 1 ).…”

Section: Introductionmentioning

confidence: 99%

Volatile Anesthetics, Not Intravenous Anesthetic Propofol Bind to and Attenuate the Activation of Platelet Receptor Integrin αIIbβ3

Yuki

Shimaoka

et al. 2013

PLoS ONE

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BackgroundIn clinical reports, the usage of isoflurane and sevoflurane was associated with more surgical field bleeding in endoscopic sinus surgeries as compared to propofol. The activation of platelet receptor αIIbβ3 is a crucial event for platelet aggregation and clot stability. Here we studied the effect of isoflurane, sevoflurane, and propofol on the activation of αIIbβ3.MethodsThe effect of anesthetics on the activation of αIIbβ3 was probed using the activation sensitive antibody PAC-1 in both cell-based (platelets and αIIbβ3 transfectants) and cell-free assays. The binding sites of isoflurane on αIIbβ3 were explored using photoactivatable isoflurane (azi-isoflurane). The functional implication of revealed isoflurane binding sites were studied using alanine-scanning mutagenesis.ResultsIsoflurane and sevoflurane diminished the binding of PAC-1 to wild-type αIIbβ3 transfectants, but not to the high-affinity mutant, β3-N305T. Both anesthetics also impaired PAC-1 binding in a cell-free assay. In contrast, propofol did not affect the activation of αIIbβ3. Residues adducted by azi-isoflurane were near the calcium binding site (an important regulatory site termed SyMBS) just outside of the ligand binding site. The mutagenesis experiments demonstrated that these adducted residues were important in regulating integrin activation.ConclusionsIsoflurane and sevoflurane, but not propofol, impaired the activation of αIIbβ3. Azi-isoflurane binds to the regulatory site of integrin αIIbβ3, thereby suggesting that isoflurane blocks ligand binding of αIIbβ3 in not a competitive, but an allosteric manner.

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Section: Introductionmentioning

confidence: 99%

Volatile Anesthetics, Not Intravenous Anesthetic Propofol Bind to and Attenuate the Activation of Platelet Receptor Integrin αIIbβ3

Yuki

Shimaoka

et al. 2013

PLoS ONE

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“…Moreover, although in some cases the effects in humans may not be important from the clinical point of view, it is preferable to know to what extent these drugs affect platelet aggregation. The effects of different inhaled anaesthetic agents on platelet aggregation have been widely studied, demonstrating, for example, that halothane inhibits in vitro and in vivo platelet aggregation, [1][2][3][4][5] while isoflurane appears to have any inhibitory effect. 3 ,6 The inhibitory effects of intravenous anaesthetics have also been assessed, showing that barbiturates appear to have no impact on platelet aggregation.…”

Section: Introductionmentioning

confidence: 99%

Optical aggregometry versus the PFA–100™: experimental studies in pigs treated with propofol

et al. 2001

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An experimental study of platelet aggregation was performed in 22 male Landrace x Large-White crossbred pigs treated with propofol at different doses, to compare the results of optical aggregometry with those of the PFA-100 (Dade Int., Miami, FL, USA), a new platelet function analyzer. Platelet aggregation was analyzed in basal blood samples by both methods, after which the pigs were divided into three groups: G1, anaesthetic induction with propofol (2 mg/kg intravenously (i.v.)); G2, anaesthetic induction with propofol (2 mg/kg i.v.), followed by a second dose of 1.5 mg/kg; and G3, anaesthetic induction with propofol (2 mg/kg i.v.), followed by 1 h of continuous i.v. infusion at 13 mg/kg/h. Four minutes after propofol injection, blood samples were again taken from each group and studied by both methods. In groups G2 and G3, both methods showed reduced platelet aggregation, while in group G1 neither evidenced an anti-aggregating effect of propofol. Under our experimental conditions: (1) the propofol effect on platelet aggregation depends on the plasma concentration; (2) the results obtained with the two methods are comparable; (3) PFA-100 may provide an alternative to optical aggregometry for detecting the effects of anaesthetic agents ex vivo.

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“…Reports by Ueda (1971) and O'Brien ef ul. ( 197 1) have provided evidence to suggest that volatile anesthetics could have potent and significant effects on platelet function.…”

Section: Introductionmentioning

confidence: 99%

Immediate and long‐term effects of halothane anesthesia on equine platelet function

Kelly

Steffey

McNeal

et al. 1985

Vet Pharm & Therapeutics

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The acute and long-term quantitative and qualitative effects of halothane anesthesia on equine platelet performance were studied in fourteen horses. Horses were anesthetized with only halothane in O2 for about 8.0 MAC hours. Platelet numbers declined during the anesthetic period but returned to normal within 24 h. Platelet aggregation was significantly diminished during the anesthetic period and for up to 4 days after anesthesia. A period of hyperaggregability occurred at the 7th day.

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The Effects of Volatile General Anesthetics on Adenosine Diphosphate-induced Platelet Aggregation

Cited by 60 publications

References 0 publications

Volatile Anesthetics, Not Intravenous Anesthetic Propofol Bind to and Attenuate the Activation of Platelet Receptor Integrin αIIbβ3

Volatile Anesthetics, Not Intravenous Anesthetic Propofol Bind to and Attenuate the Activation of Platelet Receptor Integrin αIIbβ3

Optical aggregometry versus the PFA–100™: experimental studies in pigs treated with propofol

Immediate and long‐term effects of halothane anesthesia on equine platelet function

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