Tom Kuusela

Human responses to upright tilt: a window on central autonomic integration

1 We examined interactions between haemodynamic and autonomic neural oscillations during passive upright tilt, to gain better insight into human autonomic regulatory mechanisms. 2 We recorded the electrocardiogram, finger photoplethysmographic arterial pressure, respiration and peroneal nerve muscle sympathetic activity in nine healthy young adults. Subjects breathed in time with a metronome at 12 breaths min−1 (0.2 Hz) for 5 min each, in supine, and 20, 40, 60, 70 and 80 deg head‐up positions. We performed fast Fourier transform (and autoregressive) power spectral analyses and integrated low‐frequency (0.05‐0.15 Hz) and respiratory‐frequency (0.15‐0.5 Hz) spectral powers. 3 Integrated areas of muscle sympathetic bursts and their low‐ and respiratory‐frequency spectral powers increased directly and significantly with the tilt angle. The centre frequency of low‐frequency sympathetic oscillations was constant before and during tilt. Sympathetic bursts occurred more commonly during expiration than inspiration at low tilt angles, but occurred equally in expiration and inspiration at high tilt angles. 4 Systolic and diastolic pressures and their low‐ and respiratory‐frequency spectral powers increased, and R‐R intervals and their respiratory‐frequency spectral power decreased progressively with the tilt angle. Low‐frequency R‐R interval spectral power did not change. 5 The cross‐spectral phase angle between systolic pressures and R‐R intervals remained constant and consistently negative at the low frequency, but shifted progressively from positive to negative at the respiratory frequency during tilt. The arterial baroreflex modulus, calculated from low‐frequency cross‐spectra, decreased at high tilt angles. 6 Our results document changes of baroreflex responses during upright tilt, which may reflect leftward movement of subjects on their arterial pressure sympathetic and vagal response relations. The intensity, but not the centre frequency of low‐frequency cardiovascular rhythms, is modulated by the level of arterial baroreceptor input. Tilt reduces respiratory gating of sympathetic and vagal motoneurone responsiveness to stimulatory inputs for different reasons; during tilt, sympathetic stimulation increases to a level that overwhelms the respiratory gate, and vagal stimulation decreases to a level below that necessary for maximal respiratory gating to occur.

Heart rate variability biofeedback increases baroreflex gain and peak expiratory flow.

Objective We evaluated heart rate variability biofeedback as a method for increasing vagal baroreflex gain and improving pulmonary function among 54 healthy adults. Methods We compared 10 sessions of biofeedback training with an uninstructed control. Cognitive and physiological effects were measured in four of the sessions. Results We found acute increases in low-frequency and total spectrum heart rate variability, and in vagal baroreflex gain, correlated with slow breathing during biofeedback periods. Increased baseline baroreflex gain also occurred across sessions in the biofeedback group, independent of respiratory changes, and peak expiratory flow increased in this group, independently of cardiovascular changes. Biofeedback was accompanied by fewer adverse relaxation side effects than the control condition. Conclusions Heart rate variability biofeedback had strong long-term influences on resting baroreflex gain and pulmonary function. It should be examined as a method for treating cardiovascular and pulmonary diseases. Also, this study demonstrates neuroplasticity of the baroreflex.

Vagal and Sympathetic Mechanisms in Patients With Orthostatic Vasovagal Syncope

BACKGROUND Autonomic and particularly sympathetic mechanisms play a central role in the pathophysiology of vasovagal syncope. We report direct measurements of muscle sympathetic nerve activity in patients with orthostatic vasovagal syncope. METHODS AND RESULTS We studied 53 otherwise healthy patients with orthostatic syncope. We measured RR intervals and finger arterial pressures and in 15 patients, peroneal nerve muscle sympathetic activity before and during passive 60 degree head-up tilt, with low-dose intravenous isoproterenol if presyncope did not develop by 15 minutes. We measured baroreflex gain before tilt with regression of RR intervals or sympathetic bursts on systolic or diastolic pressures after sequential injections of nitroprusside and phenylephrine. Orthostatic vasovagal reactions occurred in 21 patients, including 7 microneurography patients. Presyncopal and nonsyncopal patients had similar baseline RR intervals, arterial pressure, and muscle sympathetic nerve activity. Vagal baroreflex responses were significantly impaired at arterial pressures below (but not above) baseline levels in presyncopal patients. Initial responses to tilt were comparable; however, during the final 200 seconds of tilt, presyncopal patients had lower RR intervals and diastolic pressures than nonsyncopal patients and gradual reduction of arterial pressure and sympathetic activity. Frank presyncope began abruptly with precipitous reduction of arterial pressure, disappearance of muscle sympathetic nerve activity, and RR interval lengthening. CONCLUSIONS Patients with orthostatic vasovagal reactions have impaired vagal baroreflex responses to arterial pressure changes below resting levels but normal initial responses to upright tilt. Subtle vasovagal physiology begins before overt presyncope. The final trigger of human orthostatic vasovagal reactions appears to be the abrupt disappearance of muscle sympathetic nerve activity.

Anxiety and hostility are associated with reduced baroreflex sensitivity and increased beat-to-beat blood pressure variability

Objective The purpose of this study was to determine whether psychological factors are associated with heart rate variability (HRV), blood pressure variability (BPV), and baroreflex sensitivity (BRS) among healthy middle-aged men and women. Methods A population-based sample of 71 men and 79 women (35–64 years of age) was studied. Five-minute supine recordings of ECG and beat-to-beat photoplethysmographic finger systolic arterial pressure and diastolic arterial pressure were obtained during paced breathing. Power spectra were computed using a fast Fourier transform for low-frequency (0.04–0.15 Hz) and high-frequency (0.15–0.40 Hz) powers. BRS was calculated by cross-spectral analysis of R-R interval and systolic arterial pressure variabilities. Psychological factors were evaluated by three self-report questionnaires: the Brief Symptom Inventory, the shortened version of the Spielberger State-Trait Anger Expression Inventory, and the Toronto Alexithymia Scale. Results Psychological factors were not related to HRV. Anxiety was associated with decreased BRS (p = 0.001) and higher low-frequency (p = 0.002) power of systolic arterial pressure variability. These associations were independent of age, gender, other psychological factors, heart rate, and systolic and diastolic blood pressures. Hostility was an independent correlate of increased low-frequency power of diastolic arterial pressure (p = 0.001) and increased high-frequency power of systolic arterial pressure (p = 0.033) variability. Conclusions Anxiety and hostility are related to reduced BRS and increased low-frequency power of BPV. Reduced BRS reflects decreased parasympathetic outflow to the heart and may increase BPV through an increased sympathetic predominance.

Muscle sympathetic nerve activity during intense lower body negative pressure to presyncope in humans

Activation of sympathetic efferent traffic is essential to maintaining adequate arterial pressures during reductions of central blood volume. Sympathetic baroreflex gain may be reduced, and muscle sympathetic firing characteristics altered with head‐up tilt just before presyncope in humans. Volume redistributions with lower body negative pressure (LBNP) are similar to those that occur during haemorrhage, but limited data exist describing arterial pressure–muscle sympathetic nerve activity (MSNA) relationships during intense LBNP. Responses similar to those that occur in presyncopal subjects during head‐up tilt may signal the beginnings of cardiovascular decompensation associated with haemorrhage. We therefore tested the hypotheses that intense LBNP disrupts MSNA firing characteristics and leads to a dissociation between arterial pressure and sympathetic traffic prior to presyncope. In 17 healthy volunteers (12 males and 5 females), we recorded ECG, finger photoplethysmographic arterial pressure and MSNA. Subjects were exposed to 5 min LBNP stages until the onset of presyncope. The LBNP level eliciting presyncope was denoted as 100% tolerance, and then data were assessed relative to this normalised maximal tolerance by expressing LBNP levels as 80, 60, 40, 20 and 0% (baseline) of maximal tolerance. Data were analysed in both time and frequency domains, and cross‐spectral analyses were performed to determine the coherence, transfer function and phase angle between diastolic arterial pressure (DAP) and MSNA. DAP–MSNA coherence increased progressively and significantly up to 80% maximal tolerance. Transfer functions were unchanged, but phase angle shifted from positive to negative with application of LBNP. Sympathetic bursts fused in 10 subjects during high levels of LBNP (burst fusing may reflect modulation of central mechanisms, an artefact arising from our use of a 0.1 s time constant for integrating filtered nerve activity, or a combination of both). On average, arterial pressures and MSNA decreased significantly the final 20 s before presyncope (n= 17), but of this group, MSNA increased in seven subjects. No linear relationship was observed between the magnitude of DAP and MSNA changes before presyncope (r= 0.12). We report three primary findings: (1) progressive LBNP (and presumed progressive arterial baroreceptor unloading) increases cross‐spectral coherence between arterial pressure and MSNA, but sympathetic baroreflex control is reduced before presyncope; (2) withdrawal of MSNA is not a prerequisite for presyncope despite significant decreases of arterial pressure; and (3) reductions of venous return, probably induced by intense LBNP, disrupt MSNA firing characteristics that manifest as fused integrated bursts before the onset of presyncope. Although fusing of integrated sympathetic bursts may reflect a true physiological compensation to severe reductions of venous return, duplication of this finding utilizing shorter time constants for integration of the nerve signal is required.

Heart-Rate Complexity for Prediction of Prehospital Lifesaving Interventions in Trauma Patients

BACKGROUND Traditional vital signs often fail to identify critically injured patients soon enough to permit timely intervention. To improve our ability to forecast the need for prehospital lifesaving interventions (LSIs), we applied heart-rate complexity (HRC) analysis to the electrocardiogram (ECG) of patients en route to trauma centers. METHODS Analysis of ECG and clinical data from 374 patients en route by helicopter to three urban Level I trauma centers was conducted. Waveforms from 182 patients were excluded (because of ectopy, noise, or inadequate length). Of the remaining 192 patients, 54 received 66 LSIs in the field (LSI group): intubation (n = 52), cardiopulmonary resuscitation (n = 5), cricothyroidotomy (n = 2), and pneumothorax decompression (n = 7); 138 patients did not (non-LSI group). In the field, heart rate, blood pressure, and the Glasgow Coma Scale score (GCS(TOTAL)) and its motor component (GCS(MOTOR)) were recorded. ECG was recorded during flight. Ectopy-free, 800-beat sections of ECG were identified off-line and analyzed by HRC methods including Sample Entropy (SampEn) and Detrended Fluctuations Analysis (DFA). RESULTS There was no difference between LSI and non-LSI patients in heart rate or blood pressure. SampEn was lower in LSI than in non-LSI (0.88 +/- 0.03 vs. 1.11 +/- 0.03), as was DFA (1.09 +/- 0.05 vs. 1.33 +/- 0.03) and GCS(MOTOR) (3.4 +/- 0.4 vs. 5.7 +/- 0.1) (all p < 0.0001). By logistic regression, SampEn, DFA, and GCS(MOTOR) were independently associated with LSIs (area under the receiver operating characteristic curve, 0.897). CONCLUSIONS Decreased HRC is associated with LSIs in prehospital trauma patients. HRC may be useful as a new vital sign for identification of the severely injured.

Influence of microgravity on astronauts' sympathetic and vagal responses to Valsalva's manoeuvre

When astronauts return to Earth and stand, their heart rates may speed inordinately, their blood pressures may fall, and some may experience frank syncope. We studied brief autonomic and haemodynamic transients provoked by graded Valsalva manoeuvres in astronauts on Earth and in space, and tested the hypothesis that exposure to microgravity impairs sympathetic as well as vagal baroreflex responses. We recorded the electrocardiogram, finger photoplethysmographic arterial pressure, respiration and peroneal nerve muscle sympathetic activity in four healthy male astronauts (aged 38–44 years) before, during and after the 16 day Neurolab space shuttle mission. Astronauts performed two 15 s Valsalva manoeuvres at each pressure, 15 and 30 mmHg, in random order. Although no astronaut experienced presyncope after the mission, microgravity provoked major changes. For example, the average systolic pressure reduction during 30 mmHg straining was 27 mmHg pre‐flight and 49 mmHg in flight. Increases in muscle sympathetic nerve activity during straining were also much greater in space than on Earth. For example, mean normalized sympathetic activity increased 445 % during 30 mmHg straining on earth and 792 % in space. However, sympathetic baroreflex gain, taken as the integrated sympathetic response divided by the maximum diastolic pressure reduction during straining, was the same in space and on Earth. In contrast, vagal baroreflex gain, particularly during arterial pressure reductions, was diminished in space. This and earlier research suggest that exposure of healthy humans to microgravity augments arterial pressure and sympathetic responses to Valsalva straining and differentially reduces vagal, but not sympathetic baroreflex gain.

Loss of complexity characterizes the heart rate response to experimental hemorrhagic shock in swine.

Objective:To improve our ability to identify physiologic deterioration caused by critical illness, we applied nonlinear and frequency-domain analytical methods to R-to-R interval (RRI) and systolic arterial pressure (SAP) time series during hemorrhagic shock. Design:Prospective, randomized, controlled trial. Setting:Animal laboratory of a government research institute. Subjects:Twenty swine (weight 36.4 ± 0.11 kg). Interventions:Fixed-volume hemorrhage followed by resuscitation; off-line analysis of RRI and SAP data. Measurements and Main Results:Anesthetized swine (shock group, n = 12) underwent withdrawal of 30 mL/kg blood in 10 mL/kg decrements. A control group (n = 8) received maintenance fluids only. Electrocardiogram and arterial pressure waveforms were acquired at 500 Hz. Eight hundred-beat data sets were analyzed at six time points: at baseline, after each blood withdrawal, after lactated Ringers resuscitation, and after infusion of shed blood. Nonlinear methods were used to estimate the complexity (approximate entropy, sample entropy, Lempel-Ziv entropy, normalized entropy of symbol dynamics), RRI bits per word, and fractal dimension by curve lengths and by dispersion analysis of the RRI and SAP time series. Fast Fourier transformation was used to measure the high-frequency and low-frequency powers of RRI and SAP. Baroreflex sensitivity was assessed in the time domain with the sequence method. Hemorrhagic shock caused decreases in RRI complexity as quantified by approximate entropy, sample entropy, and symbol dynamics; these changes were reversed by resuscitation. Similar but statistically insignificant changes in fractal dimension by curve lengths were seen. RRI high-frequency power decreased with hemorrhagic shock—indicating withdrawal of vagal cardiac input—and was restored by resuscitation. Similar changes in baroreflex sensitivity were seen. Hemorrhagic shock did not affect SAP complexity. Conclusions:Hemorrhagic shock caused a reversible decrease in RRI complexity; these changes may be mediated by changes in vagal cardiac control. Assessment of RRI complexity may permit identification of casualties with hemorrhagic shock.

The role of heart rate variability in risk stratification for adverse postoperative cardiac events.

There is growing evidence of a strong association between the compromised autonomic nervous system and sudden cardiac death. Heart rate variability (HRV) measures are widely used to measure alterations in the autonomic nervous system. Several studies with cardiac patients show that decreased HRV as well as baroreceptor dysfunction are more powerful predictors for sudden cardiac death than established clinical predictors such as left ventricular ejection fraction. One-third of all postoperative complications and more than half of the deaths are due to cardiac complications. Several risk indices are useful for immediate perioperative short-term, but not for long-term outcome risk stratification of an individual patient. Currently, there are no clinically assimilated methods for long-term postoperative risk assessment. Recently, few studies have shown that preoperatively decreased HRV can independently predict postoperative long-term mortality. Further studies with surgical patients are needed to establish a possible predictive value of preoperative baroreceptor dysfunction, alone and combined with HRV, for short- and long-term postoperative outcome.

Photoacoustic Gas Analysis Using Interferometric Cantilever Microphone

Abstract Theoretical considerations and a simple but realistic model of the function of the cantilever‐based photoacoustic trace gas system are presented. The essential features of the cantilever dynamics, thermal characteristics, and noise models are derived. Some other related constructions are shown with the practical implementations of the real system.