Hemodynamic responses to head-up tilt after spinal cord injury support a role for the mid-thoracic spinal cord in cardiovascular regulation.

BACKGROUND: Data showing a role for the mid-thoracic spinal cord (SC) in the control of hemodynamic changes is scarce despite existing evidence for its involvement in autonomic regulation. STUDY DESIGN: On the basis of the open label prospective series comparing three groups. OBJECTIVE: To determine whether the mid-thoracic SC has a role in hemodynamic regulation during head-up tilt (HUT). SETTING: Spinal Research Laboratory, Loewenstein Rehabilitation Hospital. METHODS: A total of 13 healthy control subjects, 10 patients with T(4)-T(6) paraplegia and 11 with C(4)-C(7) tetraplegia were examined during supine rest and during HUT. Heart rate (HR), blood pressure (BP), HR spectral components (lower frequency fluctuation (LF), higher frequency fluctuations (HF) and LF/HF) and cerebral blood flow velocity (CBFV) were continuously measured or calculated. RESULTS: BP response to HUT differed among these groups (P<0.02). During HUT, BP decreased markedly in the tetraplegia group (from a mean value of 81.65 to 67.69 mm Hg), and increased in the control groups (from 92.89 to 95.44 mm Hg) and in the T(4)-T(6) paraplegia group (from 96.24 to 97.86 mm Hg). Significant correlation was found in the control and tetraplegia groups between increases in HR LF/HF and HR at HUT (r>0.7; P<0.01). No such correlation was found in the paraplegia group. HUT effect on HR and CBFV was significant in all groups (P<0.001), but group differences were statistically non-significant. CONCLUSION: Findings were generally compatible with those of comparable previously published studies, but they also support a role for the mid-thoracic SC in hemodynamic regulation, which should be considered in clinical setting and in research.

Cold pressor test in tetraplegia and paraplegia suggests an independent role of the thoracic spinal cord in the hemodynamic responses to cold.

BACKGROUND: Cold application to the hand (CAH) is associated in healthy people with increase in heart rate (HR) and blood pressure (BP). OBJECTIVE: To study hemodynamic responses to CAH in humans following spinal cord injuries of various levels, and examine the effect of spinal cord integrity on the cold pressor response. DESIGN: An experimental controlled study. SETTING: The spinal research laboratory, Loewenstein Hospital, Raanana, Israel. SUBJECTS: Thirteen healthy subjects, 10 patients with traumatic T(4-6) paraplegia and 11 patients with traumatic C(4-7) tetraplegia. MAIN OUTCOME MEASURES: HR, BP, HR and BP spectral components (low frequency, LF; high frequency, HF; LF/HF), cerebral blood flow velocity (CBFV) and cerebrovascular resistance index (CVRi). METHODS: The outcome measures of the three subject groups monitored for HR, BP and CBFV were compared from 5 min before to 5 min after 40-150 s of CAH. The recorded signals were digitized online and analyzed offline in both the time and frequency domains. RESULTS: During CAH, HR and CVRi increased significantly in all subject groups (P<0.001), and BP in control subjects and in the tetraplegia group (P<0.01). BP increase was not statistically significant in paraplegia, and CBFV, HR LF, HR HF and BP LF did not change significantly during CAH in any group. CONCLUSIONS: The CAH effect in tetraplegia and the suppressed BP increase in paraplegia, supported by the other findings, suggest a contribution of an independent thoracic spinal mechanism to the cold pressor response.

Modified cold pressor test by cold application to the foot after spinal cord injury: suggestion of hemodynamic control by the spinal cord.

OBJECTIVE: Study hemodynamic responses to cold application to the foot (CAF) to explore the autonomic cardiovascular control by the spinal cord. DESIGN: Controlled experimental study. Hemodynamic variables were measured or calculated for 13 healthy subjects, 10 patients with traumatic T4-T6 paraplegia, and 11 patients with traumatic C4-C7 tetraplegia. Subjects were continuously monitored for heart rate (HR), blood pressure (BP), and cerebral blood-flow velocity (CBFV) from 5 mins before to 5 mins after 40-120 secs of CAF by ice water foot immersion. The recorded signals were digitized online and analyzed offline in the time and frequency domains. RESULTS: During CAF, HR increased in the control group but decreased in patients (P < 0.001). BP increased significantly in the control and tetraplegia groups (P < 0.001) and nonsignificantly in the paraplegia group. HR and BP spectral components (LF, HF, LF/HF) did not change significantly. CBFV increased significantly in the patient groups (P < 0.05) but not in the control subjects. The cerebrovascular resistance increased significantly in the control and tetraplegia groups (P < 0.001), but not in the paraplegia group. CONCLUSIONS: The findings support the presence of hemodynamic autonomic control by the spinal cord and show that responses to CAF can be used to assess its integrity.

Hemodynamic effects of liquid food ingestion in mid-thoracic paraplegia: is supine postprandial hypotension related to thoracic spinal cord damage?

BACKGROUND: Postprandial hypotension (PPH) appears in various conditions with autonomic failure and was symptomatic in a patient with thoracic paraplegia, but was not remarkable in patients with tetraplegia. OBJECTIVE: To determine whether the pathology causing PPH may include a thoracic but not a cervical spinal cord lesion (SCL). DESIGN: An experimental controlled study. SETTING: The spinal research laboratory, Loewenstein Hospital, Raanana, Israel. SUBJECTS: Thirteen healthy subjects, 10 patients with traumatic T(4)-T(6) paraplegia, and 11 patients with traumatic C(4)-C(7) tetraplegia. MAIN OUTCOME MEASURES: Heart rate (HR), blood pressure (BP), HR and BP spectral components (LF, HF, LF/HF), cerebral blood flow velocity (CBFV), and cerebrovascular resistance index (CVRi). METHODS: The effects of a standard liquid meal on the outcome measures were compared between the three subject groups monitored for HR, BP, and CBFV, from 55 min before to 45 min after the start of the meal. The recorded signals were digitized online and analyzed off-line in the time and frequency domains. RESULTS: After meal, BP decreased only in the paraplegia group (P<0.01), HR increased more prominently in this group (P<0.01), CVRi tended to decrease only in the paraplegia group, CBFV did not change significantly in any group, and HR LF/HF increased (P<0.001) in all groups but tended to increase more in paraplegia. CONCLUSIONS: Patients with mid-thoracic SCL may develop PPH. The pathology causing PPH can include a thoracic but not a cervical SCL. The normal hemodynamic reaction to liquid meal ingestion is mediated through the mid-thoracic spinal cord. The sympathovagal balance increases after food ingestion, more prominently in patients with PPH, and cerebrovascular resistance changes during PPH may help maintain the cerebral circulation.

Algorithm for ventricular capture verification based on the mechanical evoked response.

Automatic pacemaker capture verification is important for maintaining safety and low energy consumption in pacemaker patients. A new algorithm was developed, based on impedance measurement between pacing electrode poles, which reflects the distribution of the conducting medium between the poles and changes with effective contraction. Data acquired during pacemaker implant in 17 subjects were analysed, with intracardiac impedance recorded while pacing was performed in the ventricle at varying energies, resulting in multiple-captured and non-captured beats. The impedance signals of all captured/non-captured beats were analysed using three different algorithms, based on the morphology of the impedance signal. The algorithm decision for each beat was compared with an actual capture or non-capture, as determined from the simultaneous recording of surface ECG. Two of the three algorithms (Z1 and Zn) were based on impedance values, and one (Z'n) was based on the first derivative of the impedance. Z1 was based on a single sample, whereas Z'n and Z'n were based on several samples in each beat. The total accuracy for each was Z1: 43%, Zn: 87%, Z'n: 92%. It was concluded that impedance-based capture verification is feasible, that a multiple rather than single sample approach for signal classification is both feasible and superior, and that first derivative analysis with multiple samples (Z'n) provides the best results.

Phase-averaged characterization of respiratory sinus arrhythmia pattern.

A method for the accurate time-domain characterization of respiratory sinus arrhythmia (RSA) pattern is presented and applied to two groups of healthy subjects to lay the baseline of RSA patterns and to underlay their features: response to standing, stability in successive recordings, and individuality of the shape of RSA pattern. RSA pattern is evaluated by selective averaging of heart rate (HR) changes from multiple respiratory cycles over the respiratory phase and represents the complete modulating function of HR by respiration. The RSA pattern is evaluated with free respiration and even in cases of severe arrhythmia. Estimation error is 6-8% in magnitude, phase resolution is 0.2 rad, and sensitivity margin for respiratory-related HR variability (HRV) components is 1%. RSA magnitude, phase lag, and expiration-to-inspiration time ratio are derived in addition to the entire pattern. In a group of 10 healthy young adults, a phase lag difference of 11.4 +/- 8.5% (mean +/- SD, P < 0.004) was observed between supine and standing postures, possibly ascribed to breathing mechanics. A second group of 15 healthy young adults at supine rest showed stability of the RSA pattern in successive recordings (several weeks apart) as well as individuality among subjects. This may suggest a nonscalar individual long-term index for cardiorespiratory coupling. The method is complementary to the existing statistical and spectral methods. It allows the complete characterization of the primary RSA components and may provide new insight into the effects of vagal activity and changes in clinical conditions.

A theoretical appraisal of the dependence of respiratory sinus arrhythmia on gradual vagal blockade.

MOTIVATION: The high frequency (HF) indices of heart rate variability (HRV), which reflect the magnitude of respiratory sinus arrhythmia (RSA), have been repeatedly used as measures of cardiac vagal tone. Recent studies, however, have shown experimentally that variations in these indices do not necessarily reflect proportional changes in cardiac parasympathetic outflow. OBJECTIVE: The goal of this study was to obtain a physiological-based theoretical evaluation of the relationship between RSA and cardiac vagal tone, which will help explain conflicting experimental results previously published. METHODS: We derived a theoretical model for heart rate (HR) response to gradual vagal blockade. The model implements the integral-pulse-frequency-modulation (IPFM) approach to sinoatrial (SA) node physiology. The level of vagal blockade was simulated by the addition of a cardio-selective muscarinic antagonist. RESULTS AND CONCLUSION: The derivations of the model lead to a closed set of equations, from which the dependence of the HF indices on the level of vagal blockade is deduced. It is shown that several aspects of the physiological condition may have a substantial effect on this relationship: the level of baseline vagal activity, the relationship between vagal tone and the fluctuations in its traffic, the level of sympathetic activity, etc em leader Hence, changes in the HF indices of HRV provide a plausible assessment of the changes in cardiac vagal tone only under a specific range of physiological conditions.

Very high frequency oscillations in the heart rate and blood pressure of heart transplant patients.

The authors studied the recently reported very high frequency (VHF) peaks in the heart rate (HR) and blood pressure (BP) power spectra of heart transplant (HT) patients. These VHF peaks appear at frequencies much higher than the respiratory frequency, in addition to the typical low-frequency and high-frequency peaks. Twenty-five recordings obtained from 13 male HT patients (0.5-65 months following surgery) were compared with recordings from 14 normal male subjects. The ECG, continuous BP and respiration were recorded during 45min of supine rest. Eight recordings from HT patients were excluded owing to arrhythmias. Spectral analysis was performed on all other recordings. VHF peaks were found in the spectra of both BP and HR in nine recordings obtained from six HT patients. In some cases, the power in the VHF peaks was markedly higher than that of the high-frequency peak. No VHF peaks were observed in eight recordings obtained from four HT patients or in recording from any of the normal subjects. No correlation was found between the incidence of VHF peaks and time after transplant. It was proved that the VHF peaks were not artifactual, and their significance within the framework of the theory of communication systems is discussed. The presence of those peaks was attributed to vagal denervation.

Early autonomic malfunction in normotensive individuals with a genetic predisposition to essential hypertension.

One of the primary pathologies associated with hypertension is a complex autonomic dysfunction with evidence of sympathetic hyperactivity and/or vagal withdrawal. We investigated the possibility for early detection of essential hypertension on the basis of the analysis of heart rate (HR) and blood pressure fluctuations, which reflect autonomic control. Young adult normotensive offspring of one hypertensive parent (KHT; n = 12) and normotensive offspring of two normotensive parents (YN; n = 14) participated in this study. ECG, continuous blood pressure, and respiration were recorded during steady-state conditions and under various autonomic challenges. Time-frequency decomposition of these signals was performed with the use of a continuous wavelet transform. The use of the wavelet transform enables the extension of typical HR variability analysis to non-steady-state conditions. This time-dependent spectral analysis of HR allows time-dependent quantification of different spectral components reflecting the sympathetic and parasympathetic activity during rapid transitions, such as an active change in posture (CP). During an active CP from the supine to standing position, KHT demonstrated a significantly greater increase in the low-frequency fluctuations in HR than YN, indicating enhanced sympathetic involvement in the HR response to CP, and a reduced alpha-index, indicating decreased baroreceptor sensitivity. On recovery from handgrip, vagal reactivation was more sluggish in KHT. These results indicate the early existence of malfunctions in both branches of autonomic control in individuals at increased risk of hypertension.

Detection of different recumbent body positions from the electrocardiogram.

Changes in body position alter the relative angle between ECG electrodes and the mean electric axis of the heart. These changes influence the time interval during which the projection of the electric dipole, on any ECG lead, is positive (R-wave). In this study, measurements of R-wave duration (RWD) were used to identify changes in body position, and two of its uncorrelated features were used to classify each heartbeat into four basic groups relating to four body positions (supine, prone, left-side, right-side). Data were acquired from healthy volunteers during controlled condition experiments that included well-defined sequences of body positions and simultaneous recordings of ECG leads I, II and III. Results showed over 90% correct identifications of body position changes when using any of the three leads. Lead II had the best performance for the classification of body position and correctly classified 80% of heartbeats. Classification did not improve for a combination of two leads. The technique can be used to reveal additional important clinical information and can be easily implemented, in a variety of applications where ECG is recorded, such as sleep studies, Holter recordings and ischaemia detection.

Does synchronization reflect a true interaction in the cardiorespiratory system?

Cardiorespiratory synchronization, studied within the framework of phase synchronization, has recently raised interest as one of the interactions in the cardiorespiratory system. In this work, we present a quantitative approach to the analysis of this nonlinear phenomenon. Our primary aim is to determine whether synchronization between HR and respiration rate is a real phenomenon or a random one. First, we developed an algorithm, which detects epochs of synchronization automatically and objectively. The algorithm was applied to recordings of respiration and HR obtained from 13 normal subjects and 13 heart transplant patients. Surrogate data sets were constructed from the original recordings, specifically lacking the coupling between HR and respiration. The statistical properties of synchronization in the two data sets and in their surrogates were compared. Synchronization was observed in all groups: in normal subjects, in the heart transplant patients and in the surrogates. Interestingly, synchronization was less abundant in normal subjects than in the transplant patients, indicating that the unique physiological condition of the latter promote cardiorespiratory synchronization. The duration of synchronization epochs was significantly shorter in the surrogate data of both data sets, suggesting that at least some of the synchronization epochs are real. In view of those results, cardiorespiratory synchronization, although not a major feature of cardiorespiratory interaction, seems to be a real phenomenon rather than an artifact.

Autonomic response to hypobaric hypoxia assessed by time-dependent frequency decomposition of heart rate.

BACKGROUND: Acute hypoxia tolerance varies substantially among healthy individuals. We hypothesized that this variability results from a difference in autonomic (ANS) response to hypoxic stress. METHODS: Peripheral oxygen saturation, respiration and ECG were recorded from 21 healthy subjects (age, 29 +/- 7 yr) in an altitude chamber during normoxia, severe hypoxia (282 mm Hg), and mild hypoxia (360 mm Hg). Cardiovascular control was assessed by time-frequency decomposition of the heart rate signal applying the Selective Discrete Transform Algorithm (SDA). This procedure uses a variable time window, thus providing reliable physiological data even during transient states. Autonomic activity was quantified by power spectral density integrals over a 3-dimensional time-dependent spectral distribution of heart rate fluctuations. RESULTS: Subjects who had slower peripheral oxygen desaturation during severe hypoxia onset (mean 92.9 vs. 58.4 s) were those who displayed higher ANS activity in all ambient states, namely normoxia and hypoxia. These same subjects withstood hypoxia for significantly longer time periods (mean 313 vs. 244 s). CONCLUSION: Improved hypoxia tolerance is linked to enhanced autonomic activity, involving a better management of peripheral blood flow.

Time versus frequency domain techniques for assessing baroreflex sensitivity.

BACKGROUND: Newer techniques to evaluate baroreflex sensitivity (BRS) are based on the analysis of blood pressure (BP) and heart rate (HR) time series in the time or frequency domain. These novel approaches are steadily gaining popularity, since they do not require injection of vasoactive substances, nor do they rely on a complex experimental set-up. AIM: This review outlines and compares some basic features of the latest methods to assess spontaneous baroreflex function. RESULTS: Modern techniques for the estimation of spontaneous BRS are based on a variety of signal processing schemes and derive information on the baroreflex function from different perspectives. Thus factors such as respiration and other non-stationary agents may have different influences on the estimates provided by each of these approaches. Notwithstanding such individual specificity, however, it has been observed that in several physiological and pathophysiological conditions these techniques often provide comparable information on BRS changes over time, particularly when the estimates are averaged over time windows of a few minutes. CONCLUSIONS: Due to the general agreement in the pattern of BRS among most modern methods, it seems reasonable to employ the most validated of these techniques, for which data obtained in several studies are already available.

Estimation of autonomic response based on individually determined time axis.

The analysis of the time-dependence of autonomic response requires: 1. A reliable procedure for the quantification of autonomic activity under nonsteady conditions, such as an algorithm for time-frequency decomposition (ex. SDA. Wigner-Ville, or others). 2. The choice of an adequate time scale for focusing on the data: (a) the regular, universal time scale, independent of the unsteady physiological conditions, or (b) a time axis defined by specific events related to an applied perturbation, as the indicators of specific experimental or physiological conditions, so that each individual is considered according to his own intrinsic time scale. The alignment of the various subjects according to their intrinsic time scale, reflecting their individual response mechanisms, may help to disclose a common pattern of autonomic function. Using an absolute time scale to align and average results for different subjects may obscure the underlying mechanisms. Several examples of autonomic challenges are presented, in which the use of an individual time scale contributes to unveil a typical response pattern: tilt test in vasovagal syncope, the autonomic effect of active standing on hypertension, and the autonomic response to acute hypoxia.

Nonlinear dynamics applied to blood pressure control.

Hypertension is a very frequent disease, known to trigger a range of severe cardiovascular problems. The elucidation of its pathophysiology requires investigation of the mechanisms responsible for the maintenance of blood pressure in the normal system, and their possible failure in hypertension. Some of these control mechanisms display nonlinear features, indicating that the blood pressure signal might be characterized by nonlinear dynamics. Our aim was thus to investigate the nonlinear properties of the blood pressure signal under normal conditions, and in a cardiovascular system prone to hypertension. Blood pressure was investigated in young spontaneously hypertensive rats (SHR), versus their age-matched normotensive progenitors (WKY). The correlation dimension was computed as quantification of blood pressure control complexity. The parameters required for the calculation procedure of the correlation dimension were carefully determined. The results were tested with surrogate data statistics. assuming linear autocorrelated Gaussian noise as the null hypothesis. Non-integer correlation dimension values were found in both strains, with lower values for SHR than for WKY, in particular following alpha-blockade. In all cases, a statistically significant difference was found between the real and surrogate data. These results show that the nonlinear dynamics parameter D, can be used to detect differences in BP control between prehypertensive SHR and WKY rats as early as 6-7 weeks after birth.

A model for optimizing normal tissue complication probability in the spinal cord using a generalized incomplete repair scheme.

The purpose of this study was to determine the treatment protocol, in terms of dose fractions and interfraction intervals, which minimizes normal tissue complication probability in the spinal cord for a given total treatment dose and treatment time. We generalize the concept of incomplete repair in the linear-quadratic model, allowing for arbitrary dose fractions and interfraction intervals. This is incorporated into a previously presented model of normal tissue complication probability for the spinal cord. Equations are derived for both mono-exponential and bi-exponential repair schemes, regarding each dose fraction and interfraction interval as an independent parameter, subject to the constraints of fixed total treatment dose and treatment time. When the interfraction intervals are fixed and equal, an exact analytical solution is found. The general problem is nonlinear and is solved numerically using simulated annealing. For constant interfraction intervals and varying dose fractions, we find that optimal normal tissue complication probability is obtained by two large and equal doses at the start and conclusion of the treatment, with the rest of the doses equal to one another and smaller than the two dose spikes. A similar result is obtained for bi-exponential repair. For the general case where the interfraction intervals are discrete and also vary, the pattern of two large dose spikes is maintained, while the interfraction intervals oscillate between the smallest two values. As the minimum interfraction interval is reduced, the normal tissue complication probability decreases, indicating that the global minimum is achieved in the continuum limit, where the dose delivered by the "middle" fractions is given continuously at a low dose rate. Furthermore, for bi-exponential repair, it is seen that as the slow component of repair becomes increasingly dominant as the magnitude of the dose spikes decreases. Continuous low-dose-rate irradiation with dose spikes at the start and end of treatment yields the lowest normal tissue complication probability in the spinal cord, given a fixed total dose and total treatment time, for both mono-exponential and bi-exponential repair. The magnitudes of the dose spikes can be calculated analytically, and are in close agreement with the numerical results.

Diffusion anisotropy MRI for quantitative assessment of recovery in injured rat spinal cord.

Spinal cord injury and its devastating consequences are the subject of intensive research aimed at reversing or at least minimizing functional loss. Research efforts focus on either attenuating the post-injury spread of damage (secondary degeneration) or inducing some regeneration. In most of these studies, as well as in clinical situations, evaluation of the state of the injured spinal cord poses a serious difficulty. To address this problem, we carried out a diffusion-weighted MRI experiment and developed an objective routine for quantifying anisotropy in injured rat spinal cords. Rats were subjected to a contusive injury of the spinal cord caused by a controlled weight drop. Untreated control rats were compared with rats treated with T cells specific to the central nervous system self-antigen myelin basic protein, a form of therapy recently shown to be neuroprotective. After the rats were killed their excised spinal cords were fixed in formalin and imaged by multislice spin echo MRI, using two orthogonal diffusion gradients. Apparent diffusion coefficient (ADC) values and anisotropy ratio (AI) maps were extracted on a pixel-by-pixel basis. The calculated sum of AI values (SAI) for each slice was defined as a parameter representing the total amount of anisotropy. The mean-AI and SAI values increased gradually with the distance from the site of the lesion. At the site itself, the mean-AI and SAI values were significantly higher in the spinal cords of the treated animals than in the controls (P = 0.047, P = 0.028, respectively). These values were consistent with the score of functional locomotion. The difference was also manifested in the AI maps, which revealed well-organized neural structure in the treated rats but not in the controls. The SAI values, AI histograms, and AI maps proved to be useful parameters for quantifying injury and recovery in an injured spinal cord. These results encourage the development of diffusion anisotropy MRI as a helpful approach for quantifying the extent of secondary degeneration and measuring recovery after spinal cord injury. Magn Reson Med 45:1-9, 2001.

Is fatigue in patients with multiple sclerosis related to autonomic dysfunction?

Time-dependent frequency decomposition of fluctuations in cardiovascular signals (heart rate [HR], blood pressure, and blood flow) provides noninvasive and quantitative evaluation of autonomic activity during transient and steady-state conditions. This method was applied during a change of position from supine to standing in patients with multiple sclerosis (MS) who experienced unexplained fatigue and in age-matched control subjects. No difference in response to standing, as reflected in the time domain parameters (mean HR, mean blood pressure, and mean blood flow), was observed between patients with MS and control subjects. Moreover, no difference was observed in very-low-frequency and low-frequency (related to sympathetic activity) content of HR, blood pressure, blood flow, or high-frequency content of HR (related to parasympathetic activity). The only spectral estimates that showed a significant difference between groups were the ratio of low-frequency to high-frequency content of HR and low-frequency content of HR normalized to total power. Both these parameters provide an estimate of the sympathovagal balance. A significant increase in these two estimates on standing was observed in control subjects only, indicating possible impairment of the sympathovagal balance response to standing in patients with MS who experienced fatigue. The authors observed a significant age dependence between close age subgroups, which occurred in the MS group only and was observed in some of the investigated spectral estimates that reflect vagal activity. Therefore, the authors assumed that age-related reduction in vagal activity occurred earlier in patients with MS who experienced fatigue. This reduction could also explain the lack of increase in the sympathovagal balance on standing. To validate this enhanced age dependence, further investigation should be performed in a larger group of subjects with a wider age range.

Passive or active immunization with myelin basic protein promotes recovery from spinal cord contusion.

Partial injury to the spinal cord can propagate itself, sometimes leading to paralysis attributable to degeneration of initially undamaged neurons. We demonstrated recently that autoimmune T cells directed against the CNS antigen myelin basic protein (MBP) reduce degeneration after optic nerve crush injury in rats. Here we show that not only transfer of T cells but also active immunization with MBP promotes recovery from spinal cord injury. Anesthetized adult Lewis rats subjected to spinal cord contusion at T7 or T9, using the New York University impactor, were injected systemically with anti-MBP T cells at the time of contusion or 1 week later. Another group of rats was immunized, 1 week before contusion, with MBP emulsified in incomplete Freund's adjuvant (IFA). Functional recovery was assessed in a randomized, double-blinded manner, using the open-field behavioral test of Basso, Beattie, and Bresnahan. The functional outcome of contusion at T7 differed from that at T9 (2.9+/-0.4, n = 25, compared with 8.3+/-0.4, n = 12; p<0.003). In both cases, a single T cell treatment resulted in significantly better recovery than that observed in control rats treated with T cells directed against the nonself antigen ovalbumin. Delayed treatment with T cells (1 week after contusion) resulted in significantly better recovery (7.0+/-1; n = 6) than that observed in control rats treated with PBS (2.0+/-0.8; n = 6; p<0.01; nonparametric ANOVA). Rats immunized with MBP obtained a recovery score of 6.1+/-0.8 (n = 6) compared with a score of 3.0+/-0.8 (n = 5; p<0.05) in control rats injected with PBS in IFA. Morphometric analysis, immunohistochemical staining, and diffusion anisotropy magnetic resonance imaging showed that the behavioral outcome was correlated with tissue preservation. The results suggest that T cell-mediated immune activity, achieved by either adoptive transfer or active immunization, enhances recovery from spinal cord injury by conferring effective neuroprotection. The autoimmune T cells, once reactivated at the lesion site through recognition of their specific antigen, are a potential source of various protective factors whose production is locally regulated.

Bifurcation in a simple model of the cardiovascular system.

A simple nonlinear beat-to-beat model of the human cardiovascular system has been studied. The model, introduced by DeBoer et al. was a simplified linearized version. We present a modified model which allows to investigate the nonlinear dynamics of the cardiovascular system. We found that an increase in the alpha-sympathetic gain, via a Hopf bifurcation, leads to sustained oscillations both in heart rate and blood pressure variables at about 0.1 Hz (Mayer waves). Similar oscillations were observed when increasing the beta-sympathetic gain or decreasing the vagal gain. Further changes of the gains, even beyond reasonable physiological values, did not reveal another bifurcation. The dynamics observed were thus either fixed point or limit cycle. Introducing respiration into the model showed entrainment between the respiration frequency and the Mayer waves.