Over the past 3 decades, there has been an increasing interest in recording  the sympathetic nerve traffic in the skeletal muscle in humans in order to understand the physiology and pathophysiology associated with a number of conditions linked with elevated cardiovascular risk. The technique has been substantially improved in the past 10 years and has been applied to many patient groups and is now available in a number of laboratories all over the world.

Swinburne University of Technology

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Frontiers in Physiology

Integrative Physiology

Sympathetic nervous system activity in health and disease – advances with microneurographic recordings

The recent development and implementation of a catheter-based approach to denervate the renal sympathetic nerves in patients with resistant hypertension has ensured that the sympathetic nervous system (SNS) remains on center stage in cardiovascular medicine (<a href="#B6">Krum et al., 2009</a>). Given this current interest in the field, the research topic “SNS activity in health and disease—advances with microneurographic recordings” is timely as it highlights the technique of microneurography, the only method available that directly assesses sympathetic nerve firing in the clinical setting. Microneurography permits the assessment of muscle (vasoconstrictor) sympathetic nerve activity (MSNA) in humans and was introduced over 40 years ago (<a href="#B4">Hagbarth and Vallbo, 1968</a>). The eight articles compiled demonstrate how the technique has evolved and, importantly, how it has facilitated the understanding of sympathetic regulation in the healthy state as well as the sympathetic neural abnormalities underlying a number of conditions ranging from poor orthostatic control to chronic diseases linked with elevated cardiovascular risk.Sympathetic neural drive is dependent on a range of factors including race, sex, and age. This idea is developed further in the review of <a href="#B3">Fu (2012)</a> who points out that the sex and age-related differences in the prevalence of hypertension and cardiovascular disease in humans may be determined, at least in part, by differences in sympathetic control. Evidence derived from studies examining MSNA during phases of the menstrual cycle, pre- and post-menopause or during pregnancy highlights the role of sex hormones in neural control in women. Fu also draws attention to a number of conditions such as postural tachycardia, obesity, polycystic ovary syndrome, hypertensive pregnancy, essential hypertension, heart failure, and myocardial infarction where elevated sympathetic tone plays a major role in disease severity and prognosis. In line with the concept of age and sex differences in the control of SNS activity, the original contribution from <a href="#B1">Barnes et al. (2012)</a> reveals distinct differences between young women, young men, and older women with regards to sympathetic and cardiac baroreflex sensitivity in response to a hypotensive challenge, again highlighting the potential importance of female sex hormones in sympathetic control. Multiunit MSNA has also been extensively used to investigate conditions linked with orthostatic intolerance. <a href="#B5">Ichinose and Nishiyasu (2012)</a> and <a href="#B11">Ryan et al. (2012)</a> extensively studied neural responses during syncope or until the point of decompensation induced by haemorrhage. <a href="#B5">Ichinose and Nishiyasu (2012)</a> used multiunit MSNA to assess the arterial baroreflex (ABR) control under orthostatic stress and proposed that enhancement of the ABR control under orthostatic stress is an excellent defence against orthostatic hypotension and suggest that impairment of ABR control over sympathetic vasomotor activity leads to the severe hypotension associated with orthostatic syncope. <a href="#B11">Ryan et al. (2012)</a> discuss the possible mechanisms involved in eliciting alterations in sympathetic activation to explain hemodynamic decompensation during severe hypovolemia. Altogether, these articles clearly indicate that multiunit MSNA provides valuable insight into the role of the SNS in the maintenance of blood pressure during various challenges. Nonetheless, the use of multiunit MSNA is not limited to this type of investigations and, as reviewed by <a href="#B2">Bruno et al. (2012)</a>, recent studies using multiunit MSNA recordings have highlighted that the SNS may be critically influenced, at the central and at the peripheral level, by factors regulating vascular function such as nitric oxide, reactive oxygen species, endothelin, and the renin-angiotensin system. This is an important issue and certainly merits further investigation as the interaction between the SNS and endothelial function may be of important clinical significance (<a href="#B12">Sverrisdottir et al., 2010</a>).Three articles acknowledge the limitations of multiunit MSNA and emphasize the increased information associated with recording single unit MSNA. Single unit recording is technically more difficult; however, it provides a more precise description of the way vasoconstrictor neurons behave during a sympathetic burst. Upon our previous findings, we (<a href="#B7">Lambert et al., 2012</a>) highlight the fact that in conditions associated with anxiety disorders, single unit recording uncovers an atypical firing pattern of vasoconstrictor neurons even though multiunit MSNA is normal. We discuss the role of the firing pattern in sympathetic neural adaptation to long-term sympatho-inhibition seen during weight loss and the possible implication of aberration in the firing pattern in cardiovascular health taking into consideration that multiple firing during a sympathetic burst may carry adverse end organ consequences. Similarly, in their review, <a href="#B10">Murai et al. (2012)</a> emphasize that in congestive heart failure (CHF) patients, the level of multiunit MSNA is nearly maximal at rest, so the frequency of pulse synchronized MSNA cannot increase further. Thus, single unit MSNA analysis is more useful for determining actual sympathetic neural firing within one cardiac interval. For example, they show that the firing of multiple spikes within one cardiac interval is significantly augmented during the Valsalva maneuver and exercise. This response is thought to influence strong effector organ responses, increasing peripheral vascular tone and may be seen as a contributor to exercise intolerance in these patients. This idea is reinforced by the findings that aberrant sympathetic firing pattern is associated with large noradrenaline release from the heart (<a href="#B8">Lambert et al., 2011</a>). Macefield et al. (<a href="#B9">Macefield, 2012</a>) reinforces the idea of the superiority of single-unit recordings compared to multiunit MSNA in conditions such as obstructive sleep apnea, chronic obstructive pulmonary disease, and bronchiectasis. These conditions are all associated with an elevation in multiunit MSNA to the same extent to that commonly seen in CHF, yet only single-unit MSNA reveals great differences in the sympathetic firing pattern in these respiratory diseases.The SNS has long been recognized to play a central role in cardiovascular regulation, and targeting sympathetic activity is certainly a therapeutical approach in the treatment of many cardiovascular diseases. Thus, a reliable tool to assess SNS activity such as microneurography remains essential in order to comprehend the physiological mechanisms underlying disturbed SNS activity and to assess the effects of therapeutical strategies. It is anticipated that assessment of both multiunit and single unit will remain central in future investigations related to cardiovascular health.

Sympathetic nervous system activity in health and disease—advances with microneurographic recordings

The mechanisms by which blood pressure is maintained against the orthostatic stress caused by gravity's effect on the fluid distribution within the body are important issues in physiology, especially in humans who usually adopt an upright posture. Peripheral vasoconstriction and increased heart rate (HR) are major cardiovascular adjustments to orthostatic stress and comprise part of the reflex response elicited via the carotid sinus and aortic baroreceptors (arterial baroreflex: ABR) and cardiopulmonary stretch receptors (cardiopulmonary baroreflex). In a series of studies, we have been characterizing the ABR-mediated regulation of cardiovascular hemodynamics and muscle sympathetic nerve activity (MSNA) while applying orthostatic stress in humans. We have found that under orthostatic stress, dynamic carotid baroreflex responses are modulated as exemplified by the increases in the MSNA, blood pressure, and HR responses elicited by carotid baroreflex unloading and the shorter period of MSNA suppression, comparable reduction and faster recovery of mean arterial blood pressure (MAP) and greater HR response to carotid baroreflex stimulation. Our results also show that ABR-mediated beat-to-beat control over burst incidence, burst strength and total MSNA is progressively modulated as orthostatic stress is increased until induction of syncope, and that the sensitivity of ABR control over the aforementioned MSNA variables is substantially reduced during the development of syncope. We suggest that in humans, the modulation of ABR function under orthostatic stress may be one of the mechanisms by which blood pressure is maintained and orthostatic hypotension limited, and impairment of ABR control over sympathetic vasomotor activity leads to the severe hypotension associated with orthostatic syncope.

The mechanisms by which blood pressure is maintained against the orthostatic stress caused by gravity&apos;s effect on the fluid distribution within the body are important issues in physiology, especially in humans who usually adopt an upright posture. Peripheral vasoconstriction and increased heart rate (HR) are major cardiovascular adjustments to orthostatic stress and comprise part of the reflex response elicited via the carotid sinus and aortic baroreceptors (arterial baroreflex: ABR) and cardiopulmonary stretch receptors (cardiopulmonary baroreflex). In a series of studies, we have been characterizing the ABR-mediated regulation of cardiovascular hemodynamics and muscle sympathetic nerve activity (MSNA) while applying orthostatic stress in humans. We have found that under orthostatic stress, dynamic carotid baroreflex responses are modulated as exemplified by the increases in the MSNA, blood pressure, and HR responses elicited by carotid baroreflex unloading and the shorter period of MSNA suppression, comparable reduction and faster recovery of mean arterial blood pressure (MAP) and greater HR response to carotid baroreflex stimulation. Our results also show that ABR-mediated beat-to-beat control over burst incidence, burst strength and total MSNA is progressively modulated as orthostatic stress is increased until induction of syncope, and that the sensitivity of ABR control over the aforementioned MSNA variables is substantially reduced during the development of syncope. We suggest that in humans, the modulation of ABR function under orthostatic stress may be one of the mechanisms by which blood pressure is maintained and orthostatic hypotension limited, and impairment of ABR control over sympathetic vasomotor activity leads to the severe hypotension associated with orthostatic syncope.

Arterial baroreflex control of muscle sympathetic nerve activity under orthostatic stress in humans

The sympathetic nervous system (SNS) is known to play a pivotal role in short- and long-term regulation of different functions of the cardiovascular system. In the past decades increasing evidence demonstrated that sympathetic neural control is involved not only in the vasomotor control of small resistance arteries but also in modulation of large artery function. Sympathetic activity and vascular function, both of which are key factors in the development and prognosis of cardiovascular events and disease, are linked at several levels. Evidence from experimental studies indicates that the SNS is critically influenced, at the central and also at the peripheral level, by the most relevant factors regulating vascular function, such as nitric oxide (NO), reactive oxygen species (ROS), endothelin (ET), the renin-angiotensin system. Additionally, there is indirect evidence of a reciprocal relationship between endothelial function and activity of the SNS. A number of cardiovascular risk factors and diseases are characterized both by increased sympathetic outflow and decreased endothelial function. In healthy subjects, muscle sympathetic nerve activity (MSNA) appears to be related to surrogate markers of endothelial function, and an acute increase in sympathetic activity has been associated with a decrease in endothelial function in healthy subjects. However, direct evidence of a cause-effect relationship from human studies is scanty. In humans large artery stiffness has been associated with increased sympathetic discharge, both in healthy subjects and in renal transplant recipients. Peripheral sympathetic discharge is also able to modulate wave reflection. On the other hand, large artery stiffness can interfere with autonomic regulation by impairing carotid baroreflex sensitivity.

The sympathetic nervous system (SNS) is known to play a pivotal role in short- and long-term regulation of different functions of the cardiovascular system. In the past decades increasing evidence demonstrated that sympathetic neural control is involved not only in the vasomotor control of small resistance arteries but also in modulation of large artery function. Sympathetic activity and vascular function, both of which are key factors in the development and prognosis of cardiovascular events and disease, are linked at several levels. Evidence from experimental studies indicates that the SNS is critically influenced, at the central and also at the peripheral level, by the most relevant factors regulating vascular function, such as nitric oxide (NO), reactive oxygen species (ROS), endothelin (ET), the renin-angiotensin system. Additionally, there is indirect evidence of a reciprocal relationship between endothelial function and activity of the SNS. A number of cardiovascular risk factors and diseases are characterized both by increased sympathetic outflow and decreased endothelial function. In healthy subjects, muscle sympathetic nerve activity (MSNA) appears to be related to surrogate markers of endothelial function, and an acute increase in sympathetic activity has been associated with a decrease in endothelial function in healthy subjects. However, direct evidence of a cause-effect relationship from human studies is scanty. In humans large artery stiffness has been associated with increased sympathetic discharge, both in healthy subjects and in renal transplant recipients. Peripheral sympathetic discharge is also able to modulate wave reflection. On the other hand, large artery stiffness can interfere with autonomic regulation by impairing carotid baroreflex sensitivity.

Sympathetic regulation of vascular function in health and disease

This article reviews microneurographic research on sympathetic neural control in women under both physiological and pathophysiological conditions across the lifespan. Specifically, the effects of sex, age, race, the menstrual cycle, oral contraceptives, estrogen replacement therapy, and normal pregnancy on neural control of blood pressure in healthy women are reviewed. In addition, sympathetic neural activity during neurally mediated (pre)syncope, the Postural Orthostatic Tachycardia Syndrome (POTS), obesity, the Polycystic Ovary Syndrome (PCOS), gestational hypertension, and preeclampsia, chronic essential hypertension, heart failure, and myocardial infarction in women are also reviewed briefly. It is suggested that microneurographic studies provide valuable information regarding autonomic circulatory control in women of different ages and in most cases, excessive sympathetic activation is associated with specific medical conditions regardless of age and sex. In some situations, sympathetic inhibition or withdrawal may be the underlying mechanism. Information gained from previous and recent microneurographic studies has significant clinical implications in women's health, and in some cases could be used to guide therapy if more widely available.

This article reviews microneurographic research on sympathetic neural control in women under both physiological and pathophysiological conditions across the lifespan. Specifically, the effects of sex, age, race, the menstrual cycle, oral contraceptives, estrogen replacement therapy, and normal pregnancy on neural control of blood pressure in healthy women are reviewed. In addition, sympathetic neural activity during neurally mediated (pre)syncope, the Postural Orthostatic Tachycardia Syndrome (POTS), obesity, the Polycystic Ovary Syndrome (PCOS), gestational hypertension, and preeclampsia, chronic essential hypertension, heart failure, and myocardial infarction in women are also reviewed briefly. It is suggested that microneurographic studies provide valuable information regarding autonomic circulatory control in women of different ages and in most cases, excessive sympathetic activation is associated with specific medical conditions regardless of age and sex. In some situations, sympathetic inhibition or withdrawal may be the underlying mechanism. Information gained from previous and recent microneurographic studies has significant clinical implications in women&apos;s health, and in some cases could be used to guide therapy if more widely available.

Microneurographic research in women

The magnitude of decrease in blood pressure (BP) during a vasoactive drug bolus may be associated with the calculated baroreflex sensitivity (BRS). The purpose of the present study was to evaluate whether sympathetic and/or cardiac BRS relates to the extent of change in BP and whether this was altered by sex hormones. Fifty-one young women (27 ± 1 years), 14 older women (58 ± 1 years), and 36 young men (27 ± 1 years) were studied. Heart rate, BP, and muscle sympathetic nerve activity (MSNA) were monitored. Sympathetic BRS was analyzed using the slope of the MSNA-diastolic blood pressure (DBP) relationship and cardiac BRS was analyzed using the R–R interval-systolic blood pressure (SBP) relationship. Young women and men had similar mean arterial pressures (MAP, 91 ± 1 vs. 90 ± 1 mmHg), cardiac BRS (19 ± 1 vs. 21 ± 2 ms/mmHg), and sympathetic BRS (−6 ± 1 vs. −7 ± 1 AU/beat/mmHg), respectively. Older women had higher MAP (104 ± 4 mmHg, p < 0.05) and lower cardiac BRS (7 ± 1 ms/mmHg, p < 0.05), but similar sympathetic BRS (−8 ± 1 AU/beat/mmHg). There was no association between BP transients with either cardiac or sympathetic BRS in young women. In the older women, the drop in SBP, DBP, and MAP were associated with cardiac BRS (r = 0.60, r = 0.59, and r = 0.70, respectively; p < 0.05), but not sympathetic BRS. The decrease in SBP was positively related to cardiac BRS in young men (r = 0.41; p < 0.05). However, there was no relationship between the decrease in BP and sympathetic BRS. This indicates that older women and young men with low cardiac BRS have larger transients in BP during nitroprusside. This suggests a more prominent role for cardiac (as opposed to sympathetic) BRS in responding to acute BP changes in young men and older women. The fact that these relationships do not exist in young women suggest that the female sex hormones influence baroreflex responses.

The magnitude of decrease in blood pressure (BP) during a vasoactive drug bolus may be associated with the calculated baroreflex sensitivity (BRS). The purpose of the present study was to evaluate whether sympathetic and/or cardiac BRS relates to the extent of change in BP and whether this was altered by sex hormones. Fifty-one young women (27 ± 1 years), 14 older women (58 ± 1 years), and 36 young men (27 ± 1 years) were studied. Heart rate, BP, and muscle sympathetic nerve activity (MSNA) were monitored. Sympathetic BRS was analyzed using the slope of the MSNA-diastolic blood pressure (DBP) relationship and cardiac BRS was analyzed using the R–R interval-systolic blood pressure (SBP) relationship. Young women and men had similar mean arterial pressures (MAP, 91 ± 1 vs. 90 ± 1 mmHg), cardiac BRS (19 ± 1 vs. 21 ± 2 ms/mmHg), and sympathetic BRS (−6 ± 1 vs. −7 ± 1 AU/beat/mmHg), respectively. Older women had higher MAP (104 ± 4 mmHg, p &lt; 0.05) and lower cardiac BRS (7 ± 1 ms/mmHg, p &lt; 0.05), but similar sympathetic BRS (−8 ± 1 AU/beat/mmHg). There was no association between BP transients with either cardiac or sympathetic BRS in young women. In the older women, the drop in SBP, DBP, and MAP were associated with cardiac BRS (r = 0.60, r = 0.59, and r = 0.70, respectively; p &lt; 0.05), but not sympathetic BRS. The decrease in SBP was positively related to cardiac BRS in young men (r = 0.41; p &lt; 0.05). However, there was no relationship between the decrease in BP and sympathetic BRS. This indicates that older women and young men with low cardiac BRS have larger transients in BP during nitroprusside. This suggests a more prominent role for cardiac (as opposed to sympathetic) BRS in responding to acute BP changes in young men and older women. The fact that these relationships do not exist in young women suggest that the female sex hormones influence baroreflex responses.

Association of Cardiac Baroreflex Sensitivity with Blood Pressure Transients: Influence of Sex and Menopausal Status

Because the cardiovascular system and respiration are so intimately coupled, disturbances in respiratory control often lead to disturbances in cardiovascular control. Obstructive Sleep Apnea (OSA), Chronic Obstructive Pulmonary Disease (COPD), and Bronchiectasis (BE) are all associated with a greatly elevated muscle vasoconstrictor drive (muscle sympathetic nerve activity, MSNA). Indeed, the increase in MSNA is comparable to that seen in congestive heart failure (CHF), in which the increase in MSNA compensates for the reduced cardiac output and thereby assists in maintaining blood pressure. However, in OSA – but not COPD or BE – the increase in MSNA can lead to hypertension. Here, the features of the sympathoexcitation in OSA, COPD, and BE are reviewed in terms of the firing properties of post-ganglionic muscle vasoconstrictor neurons. Compared to healthy subjects with low levels of resting MSNA, single-unit recordings revealed that the augmented MSNA seen in OSA, BE, COPD, and CHF were each associated with an increase in firing probability and mean firing rates of individual neurons. However, unlike patients with heart failure, all patients with respiratory disease exhibited an increase in multiple within-burst firing which, it is argued, reflects an increase in central sympathetic drive. Similar patterns to those seen in OSA, COPD, and BE were seen in healthy subjects during an acute increase in muscle vasoconstrictor drive. These observations emphasize the differences by which the sympathetic nervous system grades its output in health and disease, with an increase in firing probability of active neurons and recruitment of additional neurons being the dominant mechanisms.

Because the cardiovascular system and respiration are so intimately coupled, disturbances in respiratory control often lead to disturbances in cardiovascular control. Obstructive Sleep Apnea (OSA), Chronic Obstructive Pulmonary Disease (COPD), and Bronchiectasis (BE) are all associated with a greatly elevated muscle vasoconstrictor drive (muscle sympathetic nerve activity, MSNA). Indeed, the increase in MSNA is comparable to that seen in congestive heart failure (CHF), in which the increase in MSNA compensates for the reduced cardiac output and thereby assists in maintaining blood pressure. However, in OSA &#x2013; but not COPD or BE &#x2013; the increase in MSNA can lead to hypertension. Here, the features of the sympathoexcitation in OSA, COPD, and BE are reviewed in terms of the firing properties of post-ganglionic muscle vasoconstrictor neurons. Compared to healthy subjects with low levels of resting MSNA, single-unit recordings revealed that the augmented MSNA seen in OSA, BE, COPD, and CHF were each associated with an increase in firing probability and mean firing rates of individual neurons. However, unlike patients with heart failure, all patients with respiratory disease exhibited an increase in multiple within-burst firing which, it is argued, reflects an increase in central sympathetic drive. Similar patterns to those seen in OSA, COPD, and BE were seen in healthy subjects during an acute increase in muscle vasoconstrictor drive. These observations emphasize the differences by which the sympathetic nervous system grades its output in health and disease, with an increase in firing probability of active neurons and recruitment of additional neurons being the dominant mechanisms.

Firing patterns of muscle vasoconstrictor neurones in respiratory disease

Elevated sympathetic activation is a characteristic feature of heart failure (HF). Excessive sympathetic activation under resting conditions has been shown to increase from the early stages of the disease, and is related to prognosis. Direct recording of multiunit efferent muscle sympathetic nerve activity (MSNA) by microneurography is the best method for quantifying sympathetic nerve activity in humans. To date, this technique has been used to evaluate the actual central sympathetic outflow to the periphery in HF patients at rest and during exercise; however, because the firing occurrence of sympathetic activation is mainly synchronized by pulse pressure, multiunit MSNA, expressed as burst frequency (bursts/min) and burst incidence (bursts/100 heartbeats), may have limitations for the quantification of sympathetic nerve activity. In HF, multiunit MSNA is near the maximum level, and cannot increase further than the heartbeat. Single-unit MSNA analysis in humans is technically demanding, but provides more detailed information regarding central sympathetic firing. Although a great deal is known about the response of multiunit MSNA to stress, little information is available regarding the responses of single-unit MSNA to physiological stress and disease. The purposes of this review are to describe the differences between multiunit and single-unit MSNA during stress and to discuss the advantages of single-unit MSNA recording in improving our understanding the pathology of increased sympathetic activity in HF.

Elevated sympathetic activation is a characteristic feature of heart failure (HF). Excessive sympathetic activation under resting conditions has been shown to increase from the early stages of the disease, and is related to prognosis. Direct recording of multiunit efferent muscle sympathetic nerve activity (MSNA) by microneurography is the best method for quantifying sympathetic nerve activity in humans. To date, this technique has been used to evaluate the actual central sympathetic outflow to the periphery in HF patients at rest and during exercise; however, because the firing occurrence of sympathetic activation is mainly synchronized by pulse pressure, multiunit MSNA, expressed as burst frequency (bursts/min) and burst incidence (bursts/100 heartbeats), may have limitations for the quantification of sympathetic nerve activity. In HF, multiunit MSNA is near the maximum level, and cannot increase further than the heartbeat. Single-unit MSNA analysis in humans is technically demanding, but provides more detailed information regarding central sympathetic firing. Although a great deal is known about the response of multiunit MSNA to stress, little information is available regarding the responses of single-unit MSNA to physiological stress and disease. The purposes of this review are to describe the differences between multiunit and single-unit MSNA during stress and to discuss the advantages of single-unit MSNA recording in improving our understanding the pathology of increased sympathetic activity in HF.

Advantage of Recording Single-Unit Muscle Sympathetic Nerve Activity in Heart Failure

Hemorrhage remains a major cause of mortality following traumatic injury in both military and civilian settings. Lower body negative pressure (LBNP) has been used as an experimental model to study the compensatory phase of hemorrhage in conscious humans, as it elicits central hypovolemia like that induced by hemorrhage. One physiological compensatory mechanism that changes during the course of central hypovolemia induced by both LBNP and hemorrhage is a baroreflex-mediated increase in muscle sympathetic nerve activity (MSNA), as assessed with microneurography. The purpose of this review is to describe recent results obtained using microneurography in our laboratory as well as those of others that have revealed new insights into mechanisms underlying compensatory increases in MSNA during progressive reductions in central blood volume and how MSNA is altered at the point of hemodynamic decompensation. We will also review recent work that has compared direct MSNA recordings with non-invasive surrogates of MSNA to determine the appropriateness of using such surrogates in assessing the clinical status of hemorrhaging patients.

Hemorrhage remains a major cause of mortality following traumatic injury in both military and civilian settings. Lower body negative pressure (LBNP) has been used as an experimental model to study the compensatory phase of hemorrhage in conscious humans, as it elicits central hypovolemia like that induced by hemorrhage. One physiological compensatory mechanism that changes during the course of central hypovolemia induced by both LBNP and hemorrhage is a baroreflex-mediated increase in muscle sympathetic nerve activity (MSNA), as assessed with microneurography. The purpose of this review is to describe recent results obtained using microneurography in our laboratory as well as those of others that have revealed new insights into mechanisms underlying compensatory increases in MSNA during progressive reductions in central blood volume and how MSNA is altered at the point of hemodynamic decompensation. We will also review recent work that has compared direct MSNA recordings with non-invasive surrogates of MSNA to determine the appropriateness of using such surrogates in assessing the clinical status of hemorrhaging patients.

Sympathetic Responses to Central Hypovolemia: New Insights from Microneurographic Recordings

In humans, sympathetic activity is commonly assessed by measuring the efferent traffic in the peroneal nerve. The firing activity is the sum of several active neurons, which have the tendency to fire together in a bursting manner. While the estimation of overall sympathetic nervous activity using this multiunit recording approach has advanced our understanding of sympathetic regulation in health and disease no information is gained regarding the underling mechanisms generating the bursts of sympathetic activity. The introduction of single-unit recording has been a major step forward, enabling the examination of specific sympathetic firing patterns in diverse clinical conditions. Disturbances in sympathetic nerve firing, including high firing probabilities, high firing rates or high incidence of multiple firing, or a combination of both may impact on noradrenaline release and effector response, and therefore have clinical implications with regards to the development and progression of target organ damage. Understanding the mechanisms and consequences of specific firing patterns would permit the development of therapeutic strategies targeting these nuances of sympathetic overdrive.

In humans, sympathetic activity is commonly assessed by measuring the efferent traffic in the peroneal nerve. The firing activity is the sum of several active neurons, which have the tendency to fire together in a bursting manner. While the estimation of overall sympathetic nervous activity using this multiunit recording approach has advanced our understanding of sympathetic regulation in health and disease no information is gained regarding the underling mechanisms generating the bursts of sympathetic activity. The introduction of single-unit recording has been a major step forward, enabling the examination of specific sympathetic firing patterns in diverse clinical conditions. Disturbances in sympathetic nerve firing, including high firing probabilities, high firing rates or high incidence of multiple firing, or a combination of both may impact on noradrenaline release and effector response, and therefore have clinical implications with regards to the development and progression of target organ damage. Understanding the mechanisms and consequences of specific firing patterns would permit the development of therapeutic strategies targeting these nuances of sympathetic overdrive.