Motor and sensory deficits are well-known consequences of spinal cord injury (SCI). During the last decade, a significant number of experimental and clinical studies have focused on the investigation of autonomic dysfunction and cardiovascular control following SCI. Numerous clinical reports have suggested that unstable blood pressure control in individuals with SCI could be responsible for their increased cardiovascular mortality. The aim of this review is to outline the incidence and pathophysiological mechanisms underlying the orthostatic hypotension that commonly occurs following SCI. We describe the clinical abnormalities of blood pressure control following SCI, with particular emphasis upon orthostatic hypotension. Possible mechanisms underlying orthostatic hypotension in SCI, such as changes in sympathetic activity, altered baroreflex function, the lack of skeletal muscle pumping activity, cardiovascular deconditioning and altered salt and water balance will be discussed. Possible alterations in cerebral autoregulation following SCI, and the impact of these changes upon cerebral perfusion are also examined. Finally, the management of orthostatic hypotension will be considered.

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Orthostatic hypotension following spinal cord injury: understanding clinical pathophysiology

Human muscle sympathetic activity (MSA) is modulated by arterial baroreflex mechanisms: the sympathetic impulses are grouped in pulse synchronous bursts occurring preferentially during transient reductions of blood pressure (Delius et al. 1972), and changes in arterial baroreceptor firing induce reciprocal changes in the strength of the MSA (Wallin et al. 1975; Wallin & Eckberg, 1982). In each subject an approximately constant baroreflex latency can be defined, i.e. a given sympathetic burst can always be related to a given cardiac cycle (Delius et al. 1972). This basic relationship is similar in all subjects despite the fact that some subjects have few, and others many, sympathetic bursts. Such interindividual differences in the amount of activity are highly reproducible over several years (Sundlof & Wallin, 1977; Fagius & Wallin, 1993).

Different methods have been used to quantify the arterial baroreflex influence on MSA. In an early study, Sundlof & Wallin (1978) described the relationship between spontaneous variations of blood pressure and nerve traffic in terms of (1) threshold (i.e. whether or not a sympathetic burst is generated) and (2) baroreflex sensitivity (i.e. the slope of the relationship between the strength of a burst and the diastolic pressure in the corresponding heart beat). The same approach has been used to study baroreflex sensitivity during sleep (Nakazato et al. 1998) and to compare groups of normotensive and hypertensive subjects (Wallin & Sundlof, 1979). More commonly, baroreflex effects on MSA have been quantified by measuring the relationship between changes in MSA and blood pressure induced by injections of vasoactive drugs. This approach has been used to study baroreflex sensitivity in healthy subjects at different ages (e.g. Ebert et al. 1992; Matsukawa et al. 1996), in association with manoeuvres (e.g. Halliwill et al. 1996), in cardiovascular diseases (e.g. Ferguson et al. 1992; Grassi et al. 1995; Carlson et al. 1996; Meyrelles et al. 1997) or after administration of anaesthetic drugs (e.g. Sellgren et al. 1994; Muzi & Ebert, 1995).

Surprisingly, neither method has been used to quantify arterial baroreflex characteristics in individual subjects. Thus, it is not known whether significant arterial baroreflex thresholds and sensitivites in MSA can be defined for all subjects, and whether, in a given subject, such measures of arterial baroreflex function are reproducible. It is also unknown whether baroreflex characteristics in MSA differ between subjects with few and many MSA bursts at rest. The aim of the present study was to answer these questions. Baroreflex threshold and sensitivity were determined from spontaneous variations of blood pressure/cardiac interval and sympathetic nerve traffic (Sundlof & Wallin, 1978). To minimize random variations in the results, a study of the method of analysis was also included.

https://physoc.onlinelibrary.wiley.com/doi/pdf/10.1111/j.1469-7793.2001.0861h.x

Two sites for modulation of human sympathetic activity by arterial baroreceptors

Nutraceuticals, vitamins, antioxidants, and minerals in the prevention and treatment of hypertension.

ObjectivesTo determine the effect of oral vitamin C supplements on ambulatory blood pressure and plasma lipids.DesignA 6-month double-blind randomized placebo-controlled cross-over study with a 1-week washout between cross-over periods.MethodsVitamin C 500 mg daily or matching placebo was given to 4

Effect of vitamin C on ambulatory blood pressure and plasma lipids in older persons

Microneurography as a tool in clinical neurophysiology to investigate peripheral neural traffic in humans

To determine whether or not there are nocturnal variations in sympathetic baroreflex sensitivity (BRS), we measured spontaneous sympathetic BRSs in eight normal subjects (average 24.5 years old) between 2300 and 0700 h. Electrocardiogram, blood pressure, polysomnography, and muscle sympathetic nerve activity (MSA) using microneurography were recorded. We defined cardiac 'baroreflex sequences' as those that contain three or more adjacent pulses, with the systolic blood pressure and the subsequent pulse interval either continuously increased or decreased. A similar analysis was applied to sympathetic BRSs. We selected three or more adjacent pulses during which diastolic blood pressures continuously increased or decreased. Total activity in MSA was defined as burst per minute x burst amplitude and we calculated the regression coefficients between the diastolic blood pressure and the subsequent total activities in MSA. The regression coefficients were classified as either negative or positive ones. When they were less than zero, we termed them 'baroreflex sequences'. Cardiac and sympathetic BRSs were estimated from the average slope of the baroreflex sequences. Sympathetic BRS was significantly lower during sleep than while subjects were awake in the evening (P < 0.05), and it remained low after the subjects woke up in the morning (P < 0.05). Conversely, cardiac BRS had a tendency to increase during sleep in the night, but not statistically significant. This sympathetic BRS pattern may contribute to diurnal haemodynamic variables and may account, at least in part, for the connection between circadian rhythm and cardiovascular disease.

Nocturnal variation in human sympathetic baroreflex sensitivity

In immunoglobulin A nephropathy (IgAN), Cox regression analysis can select independent prognostic variables for renal functional decline (RFD). However, the correlation of the selected histological variables with clinical and/or treatment variables is unknown, thereby making histology-based treatment decisions unreliable. We prospectively followed 946 Japanese patients with IgAN for a median of 66 mo. and applied structural equation modeling (SEM) to identify direct and indirect effects of histological variables on RFD as a regression line of estimated glomerular filtration rate (eGFR) via clinical variables including amount of proteinuria(UPE), eGFR, mean arterial pressure(MAP) at biopsy, and treatment variables such as steroid therapy with/without tonsillectomy(ST) and renin-angiotensin system blocker (RASB). Multi-layered correlations between the variables and RFD were identified by multivariate linear regression analysis and the models goodness of fit was confirmed. Only tubular atrophy/interstitial fibrosis (T) had an accelerative direct effect on RFD, while endocapillary hypercellularity (E) and active crescent (C) had an attenuating indirect effect via ST. S had an attenuating indirect effect via eGFR. M had accelerative indirect effect for RFD via UPE. Moreover, M and C had accelerative indirect effect via UPE, which can be controlled by ST. However, both T and S had additional indirect accelerative effects via eGFR0c or MAP, which cannot be controlled by ST. SEM identified a systemic path links between histological variables and RFD via dependent clinical and/or treatment variables. These findings lead to clinically applicable novel methodologies that can contribute to predict treatment outcomes using the Oxford classifications.

Takashi Nakazato

Papers

Nocturnal variation in human sympathetic baroreflex sensitivity

Structural modeling for Oxford histological classifications of immunoglobulin A nephropathy