Acute epinephrine test after renal sympathetic denervation in uncontrolled hypertensive patients

Abstract

Studies employing percutaneous renal sympathetic denervation (RSD) [1][2][3][4] showed a reduction in both systolic and diastolic blood pressure (BP) among refractory hypertensive patients. As we described previously [5,6], the reduction in office BP was evident from the 1st month until one year after RSD in refractory hypertensive patients. A recent study in animals showed the pathology of radiofrequencyderived RSD during the time and provided important knowledge of the mechanisms resulting in sustained BP reduction, and reported that the nerve damage post radiofrequency ablation was greatest at 7 days, with maximum functional nerve damage sustained ≤30 days. Focal terminal nerve regeneration was observed only at the sites of ablation as early as 2 months and continued to 6 months [7]. Another study reported a substantial decrease in office systolic BP in relation to the number of ablation points at 6 months [8]. To date, there is no test to prove the acute efficacy of RSD.As a hormone, epinephrine plays on closely all body tissues. Its actions vary by tissue kind and tissue manifestation of adrenergic receptors. Epinephrine acts by binding to a diversity of adrenergic receptors. Epinephrine is a nonselective agonist of altogether adrenergic receptors, comprising the major subtype's α 1 , α 2 , β 1 , β 2 , and β 3 . Its activities are to increase peripheral resistance via α1 receptordependent vasoconstriction and to growth cardiac output via its binding to β1 receptors. Based on this information, we believe that epinephrine can be used to evaluate the acute response of BP and heart rate (HR) to RSD in uncontrolled hypertensive patients.This transversal study involved 25 uncontrolled hypertensive subjects, was conducted in agreement with the Helsinki declaration and approved by the ethics committee of our institution. All subects sign up the informed consent term before inclusion. This study was piloted at the Hospital e Clínica São Gonçalo, Rio de Janeiro, Brazil. Patients were recruited from January 2015 to December 2016 from the Arrhythmias and Artificial Cardiac Pacing Service of the same hospital. Patients with the mixture of the subsequent criteria were successively enrolled: (i) mean 24-hour systolic ambulatory BP measurements (ABPM) of >130 mmHg and mean 24-hour diastolic ambulatory BP >80 mmHg, in use of at least 3 antihypertensive agents in the maximum doses prescribed or tolerated, being one of them a diuretic; (ii) a physically normal heart with an ejection fraction of >50% (Simpson's method) to CRM, without ischemia, fibrosis area, or any other disease; (iii) age of 18 to 80 years, (iv) estimated glomerular filtration rate (eGFR) >60 mL/min/1.73 m 2 estimated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation [9] (without microalbuminuria), and (vi) the capacity to read, understand, and sign the informed consent form and go to the clinical tests. The patients that presented any of the subsequent criteria were excluded: (i) pregnancy; (ii) valvular disease with significant ad...