Anesthetic myocardial protection with sevoflurane.

OBJECTIVE To examine the role of sevoflurane in myocardial protection in patients undergoing coronary artery bypass graft (CABG) surgery. DESIGN Prospective, randomized, controlled, double-blinded study. SETTING Veterans Administration Medical Center (VAMC), Buffalo, New York. SUBJECTS Twenty-one patients undergoing CABG were included in the study. Eleven patients were randomized to receive sevoflurane, and 10 patients served as controls. INTERVENTION Total intravenous anesthesia was provided for both study and control groups by infusion of propofol, fentanyl, and midazolam. Sevoflurane 2% was added to the cardioplegia solution in the experimental group. MEASUREMENTS AND MAIN RESULTS Neutrophil beta-integrins (CD11b/CD18), tumor necrosis factor alpha (TNF-alpha), and interleukin (IL)-6 were measured as indicators of the inflammatory response to myocardial ischemia-reperfusion injury. Blood samples were obtained from the aorta and coronary sinus before (T1) and immediately after cardiopulmonary bypass (CPB) (T2) and, in addition, from a peripheral artery 6 hours (T3) after CPB. Myocardial function was determined in all patients at each time point. Left ventricular stroke work index (LVSWI) was calculated as an estimation of left ventricular function. Left ventricular regional wall motion abnormality (RWMA) was assessed by transesophageal echocardiography at T1 and T2 time points. TNF-alpha was detectable only in the control group in arterial samples at T3. IL-6 levels (pg/mL) were found to be lower in the sevoflurane group compared with controls at T2 arterial circulation (38.2 +/- 21.1 v 60.6 +/- 19.1, p < 0.05) as well as in the coronary circulation (38.4 +/- 19.9 v 118.2 +/- 23.5, p < 0.01) at T2. CD11b/CD18 increased 79% after CPB in the control group while only increasing 36% in the sevoflurane group (p < 0.05). The post-CPB LVSWI was back to its baseline values in the sevoflurane group, whereas it was still significantly depressed in the control group. Eight of 10 patients in the control group showed a transient new-onset RWMA in either the septal or anteroseptal regions. Only 2 of 11 patients in the sevoflurane group showed transient RWMA of the LV. CONCLUSIONS Sevoflurane decreases the inflammatory response after CPB, as measured by the release of IL-6, CD11b/CD18, and TNF-alpha. Myocardial function after CPB, as assessed by RWMA and LVSWI, was also improved with sevoflurane. The role of sevoflurane in myocardial protection and the inflammatory response to myocardial reperfusion should be considered.

[1]  Sania T Haroun-Bizri,et al.  Does isoflurane optimize myocardial protection during cardiopulmonary bypass? , 2001, Journal of cardiothoracic and vascular anesthesia.

[2]  A. Ghini,et al.  Beneficial impact of isoflurane during coronary bypass surgery on troponin I release. , 1999, Giornale italiano di cardiologia.

[3]  M. Entman,et al.  Cytokines and the microcirculation in ischemia and reperfusion. , 1998, Journal of molecular and cellular cardiology.

[4]  F. Incardona,et al.  Endothelin-1 induces production of the neutrophil chemotactic factor interleukin-8 by human brain-derived endothelial cells. , 1998, Blood.

[5]  H. Matsuda,et al.  Interleukin-6 derived from hypoxic myocytes promotes neutrophil-mediated reperfusion injury in myocardium. , 1998, The Journal of thoracic and cardiovascular surgery.

[6]  G. Regel,et al.  Cytokines and adhesion molecules in elective and accidental trauma-related ischemia/reperfusion. , 1998, The Journal of trauma.

[7]  G. Hill.  Cardiopulmonary bypass-induced inflammation: is it important? , 1998, Journal of cardiothoracic and vascular anesthesia.

[8]  A. Harken,et al.  Increased myocardial tumor necrosis factor-alpha in a crystalloid-perfused model of cardiac ischemia-reperfusion injury. , 1998, The Annals of thoracic surgery.

[9]  K. Ichihara,et al.  Sevoflurane preserves endocardial blood flow during coronary ligation in dogs: comparison with adenosine , 1998, Acta anaesthesiologica Scandinavica.

[10]  J. Gurevitch,et al.  Anti-tumor necrosis factor-alpha improves myocardial recovery after ischemia and reperfusion. , 1997, Journal of the American College of Cardiology.

[11]  P. Gaehtgens,et al.  β2 integrins (CD11/CD18) promote apoptosis of human neutrophils , 1997, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[12]  G. Schmitz,et al.  Effects of volatile anaesthetics on human neutrophil oxidative response to the bacterial peptide FMLP. , 1997, British journal of anaesthesia.

[13]  D. Royston.  The inflammatory response and extracorporeal circulation. , 1997, Journal of cardiothoracic and vascular anesthesia.

[14]  Michael V. Cohen,et al.  Volatile Anesthetics Protect the Ischemic Rabbit Myocardium from Infarction , 1997, Anesthesiology.

[15]  S. Zahler,et al.  Halothane, Isoflurane, and Sevoflurane Reduce Postischemic Adhesion of Neutrophils in the Coronary System , 1997, Anesthesiology.

[16]  P. Pagel,et al.  Mechanism of Myocardial Protection by Isoflurane: Role of Adenosine Triphosphate‐regulated Potassium (K sub ATP) Channels , 1996, Anesthesiology.

[17]  P. Pagel,et al.  Glyburide, a KATP Channel Antagonist, Attenuates the Cardioprotective Effects of Isoflurane in Stunned Myocardium , 1996, Anesthesia and analgesia.

[18]  U. Ikeda,et al.  Expression of cytokine-induced neutrophil chemoattractant in rat cardiac myocytes. , 1995, Journal of molecular and cellular cardiology.

[19]  J. Perrard,et al.  Regulation of ICAM‐1 and IL‐6 in Myocardial Ischemia: Effect of Reperfusion a , 1994, Annals of the New York Academy of Sciences.

[20]  W. Dreyer,et al.  Kinetics of C5a release in cardiac lymph of dogs experiencing coronary artery ischemia-reperfusion injury. , 1992, Circulation research.

[21]  J. Mayer,et al.  Evidence for the role of neutrophils in reperfusion injury after cold cardioplegic ischemia in neonatal lambs. , 1992, The Journal of thoracic and cardiovascular surgery.

[22]  D. W. Wilde,et al.  Halothane alters control of intracellular Ca2+ mobilization in single rat ventricular myocytes. , 1991, Anesthesiology.

[23]  M. Arnaout,et al.  Expression of a soluble and functional form of the human beta 2 integrin CD11b/CD18. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[24]  R. Jennings,et al.  Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. , 1986, Circulation.

[25]  W J Stewart,et al.  ASE/SCA guidelines for performing a comprehensive intraoperative multiplane transesophageal echocardiography examination: recommendations of the American Society of Echocardiography Council for Intraoperative Echocardiography and the Society of Cardiovascular Anesthesiologists Task Force for Certifi , 1999, Anesthesia and analgesia.

[26]  S. Wesselingh,et al.  Cytokine mRNA expression in postischemic/reperfused myocardium. , 1995, The American journal of pathology.

[27]  B. Davidson,et al.  Effects hypoxia/reoxygenation on intracellular calcium ion homeostasis in ventricular myocytes during halothane exposure. , 1994, Advances in pharmacology.