Esmolol acutely alters oxygen supply-demand balance in exercising muscles of healthy humans

David N Proctor,J Carter Luck,Matthew D Muller,Urs A Leuenberger,Stephan R Maman

doi:10.14814/phy2.13673

David N Proctor, J Carter Luck + Show 3 more

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https://doi.org/10.14814/phy2.13673

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Abstract

Beta‐adrenoreceptor antagonists (β blockers) reduce systemic O2 delivery and blood pressure (BP) during exercise, but the subsequent effects on O2 extraction within the active limb muscles are unknown. In this study, we examined the effects of the fast‐acting, β 1 selective blocker esmolol on systemic hemodynamics and leg muscle O2 saturation (near infrared spectroscopy, NIRS) during submaximal leg ergometry. Our main hypothesis was that esmolol would augment exercise‐induced reductions in leg muscle O2 saturation. Eight healthy adults (6 men, 2 women; 23–67 year) performed light and moderate intensity bouts of recumbent leg cycling before (PRE), during (β 1‐blocked), and 45 min following (POST) intravenous infusion of esmolol. Oxygen uptake, heart rate (HR), BP, and O2 saturation (SmO2) of the vastus lateralis (VL) and medial gastrocnemius (MG) muscles were measured continuously. Esmolol attenuated the increases in HR and systolic BP during light (−12 ± 9 bpm and −26 ± 12 mmHg vs. PRE) and moderate intensity (−20 ± 10 bpm and −40 ± 18 mmHg vs. PRE) cycling (all P < 0.01). Exercise‐induced reductions in SmO2 occurred to a greater extent during the β 1‐blockade trial in both the VL (P = 0.001 vs. PRE) and MG muscles (P = 0.022 vs. PRE). HR, SBP and SmO2 were restored during POST (all P < 0.01 vs. β 1‐blocked). In conclusion, esmolol rapidly and reversibly increases O2 extraction within exercising muscles of healthy humans.

Highlights

Beta-adrenoreceptor antagonist drugs (b blockers) are the standard of care for patients with cardiac diseases such as previous myocardial infarction, stable angina, and heart failure (Freemantle et al 1999; Frishman 2013; de Shu et al 2012)
These whole limb measures of O2 extraction/venous O2 content do not indicate where these b1-induced alterations in limb O2 supply-demand are taking place, nor do they provide insight into the dynamic nature of these responses. Insight into these questions would advance our understanding of the local compensatory effects of these widely used drugs. We addressed these gaps in knowledge using esmolol, a fast-acting b1 selective blocker, in combination with the high temporal resolution of near infrared spectroscopy (NIRS)
The systolic blood pressure (BP) response was attenuated by esmolol (P < 0.001 compared to the Pretrial) and was restored 45 min after ending the esmolol infusion (P = 0.001 compared to beta-blocked trial)

Summary

Introduction

Beta-adrenoreceptor antagonist drugs (b blockers) are the standard of care for patients with cardiac diseases such as previous myocardial infarction, stable angina, and heart failure (Freemantle et al 1999; Frishman 2013; de Shu et al 2012). Esmolol and Muscle O2 Extraction taking these medications due to limitations in systemic O2 delivery (via an impaired ability to raise heart rate and cardiac output) and active muscle blood flow (via a reduction in local perfusion pressure and/or augmented sympathetic vasoconstriction) (Hughson and Kowalchuk 1991; Pawelczyk et al 1992; Tesch 1985). For people taking b blockers and performing activities of daily living (e.g. walking, climbing stairs, yard/house work), further widening of the arteriovenous O2 difference becomes an important compensatory mechanism for meeting O2 demand in peripheral tissues (Hughson and Kowalchuk 1991)

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