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Esmolol improves left ventricular function via enhanced beta-adrenergic receptor signaling in a canine model of
John V Booth1, Donat R Spahn, Robert L McRae
1Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Insights
Beta-adrenergic receptor (beta AR) antagonists like esmolol improve heart function after acute coronary syndromes. Esmolol enhances myocardial beta AR signaling, protecting the heart during reperfusion injury.
Area of Science:
- Cardiology
- Pharmacology
- Cardiovascular Research
Background:
- Limited data exists on beta-adrenergic receptor (beta AR) antagonist use post-acute coronary syndromes (ACS) and revascularization.
- Assessing beta AR antagonists for cardioprotection and improved ventricular function in this context is crucial.
Purpose of the Study:
- To investigate the effects of esmolol, an ultra-short-acting beta AR antagonist, on left ventricular function.
- To determine if esmolol treatment preserves beta AR signaling during myocardial ischemia and reperfusion.
Main Methods:
- Canine model of acute reversible coronary ischemia followed by reperfusion during cardiopulmonary bypass (CPB).
- Randomized dogs to esmolol or saline infusions during CPB (n=29).
- Measured left ventricular function, myocardial beta AR density, and adenylyl cyclase activity via biopsies and plasma catecholamines.
Main Results:
- Esmolol administration significantly improved left ventricular systolic shortening post-reperfusion compared to controls (72% vs. 48% of pre-CPB values).
- Isoproterenol-stimulated adenylyl cyclase activity increased in the esmolol group but decreased in the control group, indicating enhanced beta AR signaling.
Conclusions:
- Esmolol administration demonstrates prospective evidence of improved myocardial function following ischemia-reperfusion injury.
- The cardioprotective mechanism of esmolol involves enhanced myocardial beta AR signaling.
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.