Metoprolol and coronary artery bypass grafting surgery: does intraoperative metoprolol attenuate acute beta-adrenergic receptor desensitization during cardiac surgery?
Cardiac surgery results in significant impairment of beta-adrenergic receptor (beta AR) function and is a cause of depressed myocardial function after surgery. We previously demonstrated that acute administration of beta AR blocker during cardiopulmonary bypass (CPB) in an animal model of coronary artery bypass grafting (CABG) surgery attenuates beta AR desensitization, whereas chronic oral beta-blockade therapy in patients undergoing CABG surgery does not prevent it. Therefore we hypothesized that acute administration of metoprolol during CABG surgery would prevent acute myocardial beta AR desensitization. A placebo-controlled initial phase (n = 72) was performed whereby patients were randomized to either metoprolol 10 mg or placebo immediately before CPB. Then a second dose-finding study was performed where patients received 20 mg (n = 20) or 30 mg (n = 20) of metoprolol. Hemodynamic monitoring, atrial membrane adenylyl cyclase activity, atrial beta AR density, and postoperative outcomes were measured. All groups showed similar decreases in isoproterenol-stimulated adenylyl cyclase activity (13%-24%). Cardiac output remained similar in all 4 groups throughout the intraoperative and postoperative period. In addition, patients receiving metoprolol 20 or 30 mg had less supraventricular arrhythmias 24 h postoperatively compared with patients receiving metoprolol 10 mg or placebo. Therefore, unlike our previous animal model of CABG surgery, metoprolol did not attenuate myocardial beta AR desensitization.


CONCLUSIONS
We investigated whether IV metoprolol given during cardiac surgery attenuates myocardial beta-adrenergic receptor (beta AR) desensitization. Although metoprolol did not reduce beta AR desensitization, the incidence of supraventricular arrhythmias was reduced by 75% in patients receiving 20 mg or 30 mg metoprolol.
Booth
John V
JV
Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina 27710, USA. booth006@mc.duke.edu
Ward
Erin E
EE
Colgan
Kelly C
KC
Funk
Bonita L
BL
El-Moalem
Habib
H
Smith
Michael P
MP
Milano
Carmelo
C
Smith
Peter K
PK
Newman
Mark F
MF
Schwinn
Debra A
DA
D000262:Adenylyl Cyclases / Q000378:metabolism; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D000368:Aged; D002302:Cardiac Output / Q000502:physiology; D006348:Cardiac Surgical Procedures; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D001026:Coronary Artery Bypass; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D023381:Endpoint Determination; D005260:Female; D006321:Heart / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007275:Injections, Intravenous; D007432:Intraoperative Period; D008297:Male; D008790:Metoprolol / Q000008:administration & dosage / Q000627:therapeutic use*; D008875:Middle Aged; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000187:drug effects* / Q000502:physiology*; D013617:Tachycardia, Supraventricular / Q000503:physiopathology / Q000517:prevention & control
D000319:Adrenergic beta-Antagonists; D002316:Cardiotonic Agents; D011943:Receptors, Adrenergic, beta; D000262:Adenylyl Cyclases; D008790:Metoprolol