Esmolol improves left ventricular function via enhanced beta-adrenergic receptor signaling in a canine model of coronary revascularization.
BACKGROUND
Recent American Heart Association guidelines highlight the paucity of data on effectiveness and/or mechanisms underlying use of beta-adrenergic receptor (beta AR) antagonists after acute coronary syndromes in patients subsequently undergoing revascularization. It is important to assess whether beta AR antagonists might protect the heart and improve ventricular function in this scenario. The authors therefore used esmolol (an ultra-short-acting beta AR antagonist) to determine whether beta AR antagonist treatment improves left ventricular function in a canine model of acute reversible coronary ischemia followed by coronary reperfusion during cardiopulmonary bypass (CPB). The authors also tested whether the mechanism includes preserved beta AR signaling.


METHODS
Dogs were randomized to either esmolol or saline infusions administered during CPB (n = 29). Pre-CPB and end-CPB transmyocardial left ventricular biopsies were obtained; plasma catecholamine concentrations, myocardial beta AR density, and adenylyl cyclase activity were measured. In addition, left ventricular systolic shortening and postsystolic shortening were determined immediately prior to each biopsy.


RESULTS
While beta AR density remained unchanged in each group, isoproterenol-stimulated adenylyl cyclase activity decreased 26 +/- 6% in the control group but increased 38 +/- 10% in the esmolol group (pre-CPB to end-CPB, mean +/- SD, P = 0.0001). Left ventricular systolic shortening improved in both groups after release of coronary (LAD) ligature; however, the esmolol group increased to 72 +/- 23% of pre-CPB values compared to 48 +/- 12% for the control group (P = 0.0008).


CONCLUSIONS
These data provide prospective evidence that esmolol administration results in improved myocardial function. Furthermore, the mechanism appears to involve enhanced myocardial beta AR signaling.
Booth
John V
JV
Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Spahn
Donat R
DR
McRae
Robert L
RL
Chesnut
Lynn C
LC
El-Moalem
Habib
H
Atwell
Darryl M
DM
Leone
Bruce J
BJ
Schwinn
Debra A
DA
D000262:Adenylyl Cyclases / Q000097:blood; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D002315:Cardiopulmonary Bypass; D002395:Catecholamines / Q000097:blood; D004285:Dogs; D023421:Models, Animal; D009204:Myocardial Revascularization; D011412:Propanolamines / Q000494:pharmacology*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects* / Q000502:physiology; D013599:Systole / Q000187:drug effects; D016277:Ventricular Function, Left / Q000187:drug effects*
D000319:Adrenergic beta-Antagonists; D002395:Catecholamines; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; D000262:Adenylyl Cyclases; C036604:esmolol