An Enantiomerically Pure Formulation of Esmolol Attenuates Hypotension and Preserves Heart Rate Control in Dogs
| Autor: | Justin Daller, Jeffrey S. McKee, Barrett E. Rabinow, Benjamin D Brooks, Bernhard Baumgartner, Priyanka Rohatgi |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
medicine.medical_specialty
Cardiac output Adrenergic beta-Antagonists Propanolamines Negative Inotropy Dogs Drug Stability Heart Rate Internal medicine Heart rate medicine Animals Arterial Pressure Cardiac Surgical Procedures business.industry Isoproterenol Stereoisomerism Adrenergic beta-Agonists Esmolol Anesthesiology and Pain Medicine Blood pressure Anesthesia Cardiac chronotropy Cardiology Hypotension business medicine.drug |
| Zdroj: | Anesthesiology. 121:1184-1193 |
| ISSN: | 0003-3022 |
| DOI: | 10.1097/aln.0000000000000408 |
| Popis: | Background: Esmolol is marketed as a racemate (RS-esmolol) with hypotension being the most frequently reported adverse event. Previously, it has been shown that the S-enantiomer (S-esmolol) possesses all of the heart rate (HR) control. The authors studied whether S-esmolol alone mitigates hypotension at similar degrees of HR control compared with RS-esmolol. Methods: The effects of RS- and S-esmolol on blood pressure (BP) were compared at multiple infusion rates producing similar HR control in dogs (N = 21). Differences in BP were further interrogated by monitoring global cardiovascular function and included the R-enantiomer (R-esmolol) (N = 3). Results: S-esmolol at half the rate (μg kg−1 min−1) of RS-esmolol provided the same degree of HR control over all infusion rates. RS-esmolol lowered BP by 3, 6, 11, 20, and 38 mmHg at 90, 300, 600, 1,000, and 2,000 μg kg−1 min−1, compared with 2, 4, 5, 10, and 16 mmHg at 45, 150, 300, 500, and 1,000 μg kg−1 min−1 for S-esmolol. Decreased BP with RS-esmolol was attributed to decreases in left ventricular developed pressure (LVDP) (−34 mmHg), LVdP/dt+max (−702 mmHg/s), and cardiac output (−1 l/min). R-esmolol also decreased BP (−10 mmHg), LVDP (−10 mmHg), LVdP/dt+max (−241 mmHg/s), and cardiac output (to −0.2 l/min). S-esmolol reversed these trends toward pre-esmolol values by increasing BP (+13 mmHg), LVDP (+12 mmHg), LVdP/dt+max (+76 mmHg/s), and cardiac output (+0.4 l/min). Conclusions: R-enantiomer provided no HR control, but contributed to the hypotension with RS-esmolol, which appears to be due to negative inotropy. Thus, an S-enantiomer formulation of esmolol may provide similar HR control with less hypotension. |
| Databáze: | OpenAIRE |
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