I. Pinhas

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.

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

Catz A, Bluvshtein V, Korczyn AD, Pinhas I, Gelernter I, Nissel T, Vered Y, Bornstein NM, Akselrod S: Modified cold pressor test by cold application to the foot after spinal cord injury: suggestion of hemodynamic control by the spinal cord. Am J Phys Med Rehabil 2007;86:875–882. 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.

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 T4–6 paraplegia and 11 patients with traumatic C4–7 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.

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 45 min 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.

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 T4–T6 paraplegia and 11 with C4–C7 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 T4–T6 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.

Insulin resistance in tetraplegia but not in mid-thoracic paraplegia: is the mid-thoracic spinal cord involved in glucose regulation?

Study design:Controlled experimental human study.Objectives:To assess insulin resistance (IR) in tetraplegia and paraplegia, and the role of the spinal cord (SC) in glucose regulation.Setting:Laboratory of Spinal Research, Loewenstein Rehabilitation Hospital.Methods:Glucose and insulin levels and the heart rate variation spectral components LF (low frequency), HF (high frequency) and LF/HF were studied at supine rest, head-up tilt and after a standard meal in three groups: 13 healthy subjects, 7 patients with T4–T6 paraplegia and 11 patients with C4–C7 tetraplegia.Results:Glucose and insulin increased significantly after the meal in all groups (P<0.001). Glucose increased significantly more in the tetraplegia than in the other groups (P<0.01). Increases in insulin level tended to accompany increases in LF/HF after the meal in the tetraplegia and control groups but not in the paraplegia group.Conclusion:Post-prandial IR appears in C4–C7 but not in T4–T6 SC injury. The results of the study, combined with previously published findings, are consistent with the hypotheses that IR is related to activation of the sympathetic nervous system, and that below T4 the mid-thoracic SC is involved in the regulation of glucose and insulin levels.

Bispectrum and bicoherence for the investigation of very high frequency peaks in heart rate variability

Recently (2000), we reported the occurrence of very high frequency (VHF) peaks in the heart rate (HR) and blood pressure (BP) spectra in heart transplant (HT) patients. In this study, we apply the bicoherence function, which provides an estimate of correlation between three spectral peaks, thus allowing us to determine the relations between the VHF peaks and other peaks. A statistical approach was used to determine a threshold which discerns true bispectral peaks from spurious ones for any required level of significance. 25 recordings of HR, BP and respiration were obtained from 13 male HT patients. Extensive arrhythmias prevented spectral analysis in eight recordings. VHF peaks were found in the HR and BP in nine recordings. We found two types of VHF peaks: (1) harmonics of respiration, and (2) peaks totally uncorrelated with respiration. Four recordings exhibited type-1 peaks, one recording had only type-2 peaks and four recordings had both types. The nature of the VHF peaks remains to be resolved.

Heart transplantation-spectral and bispectral analysis

Heart transplantation offers a unique view into an unusual cardiovascular system, with a denervated heart. We investigate noninvasively the compensatory cardiovascular control mechanisms, which develop following transplant. ECG, continuous blood pressure and respiration are recorded in supine position and during transition to standing, and analyzed in time and frequency domains. 25 recordings were obtained from 13 male HT patients at time after transplant (TAT) ranging 0.5-65 months. We observed an interesting evolution with TAT in heart rate response to active standing: from no response, via a slow response, to a fast increase. Another important finding was the existence of very high frequency (VHF) peaks in the power spectra of HR and BP fluctuations, in 8 recordings. Analysis using bicoherence indicates that some of those peaks are harmonics of respiration, while others originate from an unknown source. Our results indicate that with TAT, compensatory cardiovascular mechanisms develop in a biphasic process towards seemingly normal control. We found evidence for the direct effect of the old SA node on the transplanted one, yet no indication of vagal reinnervation. The presence of VHF peaks, unrelated to respiration, suggests the existence of a yet unknown control mechanism, which may be masked in normal subjects.

Heart rate recovery after exercise: a study by wavelet analysis

The reduction in heart rate (HR) during the first min of recovery immediately after a maximal exercise stress test (GXT) has recently been found to be a powerful and independent predictor of mortality. A modified continuous wavelet transform (CWT) designed in our lab, is used to perform time-dependent spectral analysis during the non steady-state conditions created by GXT. This method provides dynamic measures of the low frequency (LF) and high frequency (HF) peaks, associated with autonomic activity. A group of 18 patients underwent GXT using the Bruce Protocol. Five of 18 patients demonstrated pathologic delta HR (/spl les/ 18 bpm), while 13 patients displayed normal delta HR (/spl Gt/ 18 bpm). Patients with pathologic delta HR displayed significantly (p < 0.05) lower HF fluctuations at one-min post exercise than did the controls. Attenuated delta HR upon recovery from GXT is indeed associated with abnormal vagal function, as assessed by CWT.

Early detection of essential hypertension by time-frequency analysis

Hypertension affects approximately 25% of adults in industrialized countries and contributes significantly to morbidity and mortality from cardiovascular diseases. Young adult, normotensive offspring of one hypertensive parent (KHT, n = 12) and normotensive offspring of two normotensive parents (YN, n = 14) participated ECG, continuous blood pressure, and respiration were recorded Time-frequency decomposition of these signals was performed by a Continuous Wavelet Transform. During change in posture (CP), KHT demonstrated a significantly greater increase in the low frequency fluctuations in heart rate (HR) than YN, indicating enhanced sympathetic involvement in the HR response to CP. Upon recovery from Handgrip, vagal reactivation was more sluggish in KHT These results indicate possible malfunctions in both branches of autonomic control in individuals at increased risk of hypertension.