Effect of anaesthesia and cardiopulmonary bypass on blood endocannabinoid concentrations during cardiac surgery.
BACKGROUND
The endocannabinoid system (ECS) is an endogenous signalling system which includes the endocannabinoids anandamide (AEA) and 2-arachidonoylglycerol (2-AG) and specific G-protein-coupled endocannabinoid receptors (CB1 and CB2). Recent studies have described important roles of the peripheral ECS in human atherosclerosis, cardiometabolic disorders, heart failure, and systemic inflammation. We sought to study changes in plasma endocannabinoid concentrations during cardiac surgery (CS) under general anaesthesia with isoflurane/sufentanil, and during cardiopulmonary bypass (CPB).


METHODS
We studied 30 patients undergoing CS with CPB. All patients received midazolam and sufentanil for induction and isoflurane and sufentanil for maintenance of general anaesthesia. Blood samples were drawn before and after induction of general anaesthesia, after the beginning of surgery, during and after weaning from CPB, and after admission to intensive care unit (ICU) after surgery. Endocannabinoid measurements were performed by HPLC-tandem mass spectrometry.


RESULTS
Induction of general anaesthesia led to a significant decline in plasma AEA concentrations [from mean (sd) 0.39 (0.03) to 0.27 (0.03) ng ml(-1), P<0.01]. CPB induced a pronounced increase in 2-AG concentrations [from 112.5 (163.5) to 321.0 (120.4) ng ml(-1), P<0.01], whereas AEA concentrations remained persistently low until admission to the ICU. 2-AG concentrations returned to preoperative values after surgery.


CONCLUSIONS
General anaesthesia with isoflurane significantly reduces plasma AEA concentrations. This could be a consequence of stress reduction after loss of consciousness. The significant increase in 2-AG after initiation of CPB may be part of an inflammatory response. These findings suggest that anaesthesia and surgery have differential effects on the ECS which could have substantial clinical consequences.
Klinikum Grosshadern, Department of Anesthesiology, Ludwig-Maximilians University, Munich, Germany. florian.weis@med.uni-muenchen.de
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F
Weis
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Beiras-Fernandez
D
D
Hauer
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C
Hornuss
R
R
Sodian
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Kreth
J
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Briegel
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Schelling
D000368:Aged; D019162:Anesthetics, Combined / Q000494:pharmacology; D018681:Anesthetics, General / Q000494:pharmacology*; D018685:Anesthetics, Inhalation / Q000494:pharmacology; D018686:Anesthetics, Intravenous / Q000494:pharmacology; D001095:Arachidonic Acids / Q000097:blood; D063385:Cannabinoid Receptor Modulators / Q000097:blood*; D006348:Cardiac Surgical Procedures; D002315:Cardiopulmonary Bypass; D063388:Endocannabinoids; D005260:Female; D006801:Humans; D007432:Intraoperative Period; D007530:Isoflurane / Q000494:pharmacology; D008297:Male; D008874:Midazolam / Q000494:pharmacology; D008875:Middle Aged; D053284:Polyunsaturated Alkamides / Q000097:blood; D011446:Prospective Studies; D017409:Sufentanil / Q000494:pharmacology
D019162:Anesthetics, Combined; D018681:Anesthetics, General; D018685:Anesthetics, Inhalation; D018686:Anesthetics, Intravenous; D001095:Arachidonic Acids; D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D053284:Polyunsaturated Alkamides; D017409:Sufentanil; D007530:Isoflurane; D008874:Midazolam; C078814:anandamide