title: l-Arginine Pathway Metabolites Predict Need for Intra-operative Shunt During Carotid Endarterectomy.
abstract: OBJECTIVE
  Asymmetric dimethylarginine (ADMA) inhibits nitric oxide (NO) synthesis and is a marker of atherosclerosis. This study examined the correlation between pre-operative l-arginine and ADMA concentration during carotid endarterectomy (CEA), and jugular lactate indicating anaerobic cerebral metabolism, jugular S100B reflecting blood-brain barrier integrity, and with factors of surgical intervention.
  
  
  METHODS
  The concentration of l-arginine, ADMA, and symmetric dimethylarginine was measured in blood taken under regional anaesthesia from the radial artery of 55 patients prior to CEA. Blood gas parameters, concentration of lactate, and S100B were also serially measured in blood taken from both the radial artery and the jugular bulb before and after carotid clamping, and after release of the clamp. To estimate anaerobic metabolism, the jugulo-arterial ratio of CO2gap/oxygen extraction was calculated.
  
  
  RESULTS
  Positive correlation was found between pre-operative ADMA levels and the ratio of jugulo-arterial CO2gap/oxygen extraction during clamp and reperfusion (p = .005 and p = .01, respectively). An inverse correlation was found between the pre-operative l-arginine concentration and jugular lactate at each time point (both p = .002). The critical pre-operative level of l-arginine was determined by receiver operator curve analysis. If l-arginine was below the cutoff value of 35 μmol/L, jugular S100B concentration was higher 24 h post-operatively (p = .03), and jugular lactate levels were increased during reperfusion (p = .02). The median pre-operative concentration of l-arginine was lower in patients requiring an intra-operative shunt than in patients without need of shunt (median: 30.3 μmol/L [interquartile range 24.4-34.4 μmol/L] vs. 57.6 μmol/L [interquartile range 42.3-74.5 μmol/L]; p = .002).
  
  
  CONCLUSIONS
  High pre-operative ADMA concentration predicts poor cerebral perfusion indicated by elevated jugulo-arterial CO2gap/oxygen extraction. Low pre-operative l-arginine concentration predicts the need for a shunt. The inverse correlation between pre-operative l-arginine concentration and both jugular lactate and S100B during carotid clamping suggests a protective role of the NO donor l-arginine.
authors.affiliation: Department of Anesthesiology and Intensive Care, University of Pecs, 7624 Ifjusag u 13, Pecs, Hungary.
authors.forename: P
authors.initials: P
authors.lastname: Szabo
authors.affiliation: Department of Surgical Research and Techniques, University of Pecs, 7624 Szigeti u 12, Pecs, Hungary.
authors.forename: J
authors.initials: J
authors.lastname: Lantos
authors.affiliation: Department of Applied Chemistry, University of Debrecen, 4032 Egyetem tér 1, Debrecen, Hungary.
authors.forename: L
authors.initials: L
authors.lastname: Nagy
authors.affiliation: Department of Applied Chemistry, University of Debrecen, 4032 Egyetem tér 1, Debrecen, Hungary.
authors.forename: S
authors.initials: S
authors.lastname: Keki
authors.affiliation: Department of Anesthesiology and Intensive Care, University of Pecs, 7624 Ifjusag u 13, Pecs, Hungary.
authors.forename: E
authors.initials: E
authors.lastname: Volgyi
authors.affiliation: Department of Vascular Surgery, University of Pecs, 7635 Ifjusag 13, Pecs, Hungary.
authors.forename: G
authors.initials: G
authors.lastname: Menyhei
authors.affiliation: Department of Neurology, Odense University Hospital, Odense, Denmark; Department of Clinical Research, University of Southern Denmark, Odense, Denmark; SDR, Boulevard 29, Odense 5000, Denmark.
authors.forename: Z
authors.initials: Z
authors.lastname: Illes
authors.affiliation: Department of Anesthesiology and Intensive Care, University of Pecs, 7624 Ifjusag u 13, Pecs, Hungary. Electronic address: tihamermolnar@yahoo.com.
authors.forename: T
authors.initials: T
authors.lastname: Molnar
mesh_terms: D000368:Aged; D000693:Anaerobiosis; D019540:Area Under Curve; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood; D015415:Biomarkers / Q000097:blood; D001784:Blood Gas Analysis; D001812:Blood-Brain Barrier / Q000378:metabolism; D002199:Capillary Permeability; D016893:Carotid Stenosis / Q000097:blood / Q000175:diagnosis / Q000503:physiopathology / Q000601:surgery*; D002560:Cerebrovascular Circulation; D003250:Constriction; D016894:Endarterectomy, Carotid / Q000009:adverse effects*; D005260:Female; D006801:Humans; D007601:Jugular Veins; D019344:Lactic Acid / Q000097:blood; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012372:ROC Curve; D017534:Radial Artery; D015203:Reproducibility of Results; D012307:Risk Factors; D064568:S100 Calcium Binding Protein beta Subunit / Q000097:blood; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D064568:S100 Calcium Binding Protein beta Subunit; C579160:S100B protein, human; D019344:Lactic Acid; C024917:symmetric dimethylarginine; C018524:N,N-dimethylarginine; D001120:Arginine
keywords: Asymmetric and symmetric dimethylarginine; Carotid stenosis; Endarterectomy; Lactate; S100B; l-arginine