Current Approaches to Quantifying Tonic and Reflex Autonomic Outflows Controlling Cardiovascular Function in Humans and Experimental Animals

Abstract

The role of the autonomic nervous system in the pathophysiology of human and experimental models of cardiovascular disease is well established. In the recent years, there have been some rapid developments in the diagnostic approaches used to assess and monitor autonomic functions. Although most of these methods are devoted for research purposes in laboratory animals, many have still found their way to routine clinical practice. To name a few, direct long-term telemetry recording of sympathetic nerve activity (SNA) in rodents, single-unit SNA recording using microneurography in human subjects and spectral analysis of blood pressure and heart rate in both humans and animals have recently received an overwhelming attention. In this article, we therefore provide an overview of the methods and techniques used to assess tonic and reflex autonomic functions in humans and experimental animals, highlighting current advances available and procedure description, limitations and usefulness for diagnostic purposes.

Laterality Influences Central Integration of Baroreceptor Afferent Input in Male and Female Sprague Dawley Rats

“…The ADN in rats carries a relatively pure population of barosensitive afferent neurons (Sapru and Krieger, 1977;Sapru et al, 1981;Numao et al, 1985;Kobayashi et al, 1999), which allows for selective investigation of baroreceptor reflex function in this species. Direct electrical stimulation of these afferent fibers enables a defined control of the afferent input into the central nervous system (CNS) and, therefore, assessment of the central portion of the baroreflex arc (Ma et al, 2002;Salman, 2015). A limitation of this method, however, is that the synchronous continuous activation of essentially all afferents within the ADN differs from the physiological pattern of action potential firing, which is in phase with the arterial pressure pulse and is dependent on the recruitment pattern of individual baroreceptor fibers in relation to BP levels, the pressure thresholds of individual fibers, and fiber type (Andresen et al, 1978;Chapleau et al, 1988).…”

“…Activation of this reflex pathway induces inhibition of the sympathetic outflow to the heart and vasculature and upregulates parasympathetic drive to the heart, thereby contributing to reductions in peripheral vascular resistance, cardiac output and ultimately BP (Thomas, 2011;Salman, 2016). Electrical activation of the baroreceptor afferent neurons within the aortic depressor nerve (ADN) in rats represents a reliable method for studying physiological mechanisms pertaining to baroreflex-mediated cardiovascular regulation (Ma et al, 2002;Salman, 2015).…”

Effects of carvedilol or amlodipine on target organ damage in L-NAME hypertensive rats: their relationship with blood pressure variability

“…Spectral densities were calculated in the very low frequency (VLF) (0.1-0.2 Hz), low frequency (LF) (0.2-0.7 Hz) and high frequency (HF) (0.7-2.5 Hz) ranges. Although it is well-known that LF variability is subject to modulation of neural sympathetic vascular tone, the LF/HF ratio was used as an index of this activity, as the normalization procedure tends to reduce the effect of changes in the absolute values of BPV at the LF [16].…”

“…On the other hand, whilst amlodipine significantly reduced interday fluctuations of SAP, the effects of carvedilol on mid-term BPV did not reach statistical significance (Table 1). LF/HF ratio was calculated from BP data points, considering the fact that LF/HF has been suggested as a marker of sympathetic vascular activity [16]. Spectral analysis of BP recordings established that chronic treatment with carvedilol or amlodipine, but not with vehicle, reduced LF/HF ratio in L-NAME hypertensive rats.…”

Low intensity stimulation of aortic baroreceptor afferent fibers as a potential therapeutic alternative for hypertension treatment

“…The overall process mimics spontaneous activation of the baroreceptor reflex, albeit bypassing the process of ABP-induced activation of mechanosensitive baroreceptors in the carotid sinus and the aortic arch. This therefore enables a defined control of afferent input into the central nervous system (CNS) and fine-tunes the magnitude of ABP drop 8 . Indeed, baroreflex activation therapy (BAT) targeting the carotid sinus, via the implantable first-generation Rheo Hypertension Therapy System and then the second-generation Barostim Neo , has produced sustained decreases in SNA and ABP in humans 9 , 10 , with some preclinical studies 11 , 12 and controlled clinical trials 13 – 15 having been undertaken to grant the devices approval to treat patients with resistant hypertension.…”