Loss of consciousness as criterion of +Gz tolerance at Institute of Aviation Medicine MMA during +Gz acceleration selective test

+Gz induced loss of consciousness (G-LOC) is one of the most serious threats to aircrews flying high performance fighter aircraft. From the early beginning of use of our Centrifuge, use in selection was primary task. As a functional "endpoints" we use criteria: loss of peripheral vision, extreme pulse rate (above 180 b.p.m.), arrhythmias and loss of consciousness. The key-method in selection the candidate who tolerates +Gz stress on the best way is selection by common selective centrifuge "Test of linear increasing of acceleration" (TOLIA). We used gradual onset rate (GOR--0.1 G/s) and maximum/peak value: +5.5 Gz, +6.0 Gz and 7.0 Gz. Applied peak value depends on the goal of the test. The lowest peak value is for candidates planned for Air Academy, higher peak value is for those pilots planned for training to supersonic combat aircrafts and the highest peak value is for pilots who are planned to fly High performance combat aircrafts. We examined 2192 candidates in the last 20 years. Eleven subjects experienced G-LOC episodes. All episodes of G-LOC had occurred occasionally and without warning symptoms (loss of peripheral vision, gray out, blackout). The percentage of subjects having G-LOC episodes was 0.50%. Nine subjects experienced G-LOC during primary selection (+5.5 Gz), one G-LOC were observed at secondary selection (+6.0 Gz) and one G-LOC was observed during tertiary selection (+7 Gz). G-LOC is the only "endpoint" in the centrifuge selection which disqualifies the candidate at once and forever for planned flying duties. The other "endpoints" (loss of peripheral vision, heart rate above 180 b.p.m., arrhythmias) allow one more testing, not less than seven days later.     

A new evaluation method for +Gz tolerance with loratadine by using a near-infrared spectroscopy

Background

Loratadine (Claritin^®), an over the counter antihistamine in U.S. and UK, is acceptable for use without adverse side effects by aircrew with mild or moderate allergic or other situations requiring an antihistamine. Although +Gz (head to foot direction) tolerance testing for aircrew with loratadine has not been documented in the published literature, it is commonly accepted that loratadine dose not effect +Gz tolerance. The purpose of this study was to offer and validate a new evaluation method for +Gz tolerance testing with loratadine by using a near-infrared spectroscopy (NIRS).

Methods

A double-blind, placebo-controlled, randomized, crossover protocol was used to administer 10 mg of loratadine or placebo in nine healthy subjects. The subjects didn't wear anti-G suit. The +Gz exposure profiles consisted of, in series, a gradual onset ran (0.1 G·sec^-1) to the subject's visual end-point (peripheral light loss) or loss of consciousness (GLOC), and rapid onset run (1.0 G·sec^-1) to the subject's same end-point. In this study, G-level tolerance was defined as the +Gz level at visual end-point and/or at GLOC. As a subject's G-duration tolerance, we measured the total time (seconds) during rapid onset run. Otherwise, to confirm the effect of loratadine on +Gz tolerance, we measured the cerebral NIRS variables (hemoglobin concentration changes and tissue oxygenation index) as a new quantitative method for +Gz tolerance during a centrifuge experiments.

Results

No significant differences were observed in +Gz tolerance (+Gz level, duration time and NIRS variables) between subjects taking loratadine and placebo.

Conclusion

Our results demonstrate that loratadine has no detectable effect on +Gz tolerance by using a new method with cerebral NIRS variables and the traditional method with +Gz level and duration time. This study represents the first use of a quantitative parameter such as cerebral NIRS variables to assess the effects of a drug on acceleration tolerance.

     

Inconsistent detection of changes in cerebral blood volume by near infrared spectroscopy in standard clinical tests

The attractive possibility of near infrared spectroscopy (NIRS) to noninvasively assess cerebral blood volume and oxygenation is challenged by the possible interference from extracranial tissues. However, to what extent this may affect cerebral NIRS monitoring during standard clinical tests is ignored. To address this issue, 29 healthy subjects underwent a randomized sequence of three maneuvers that differently affect intra- and extracranial circulation: Valsalva maneuver (VM), hyperventilation (HV), and head-up tilt (HUT). Putative intracranial ("i") and extracranial ("e") NIRS signals were collected from the forehead and from the cheek, respectively, and acquired together with cutaneous plethysmography at the forehead (PPG), cerebral blood velocity from the middle cerebral artery, and arterial blood pressure. Extracranial contribution to cerebral NIRS monitoring was investigated by comparing Beer-Lambert (BL) and spatially resolved spectroscopy (SRS) blood volume indicators [the total hemoglobin concentration (tHb) and the total hemoglobin index, (THI)] and by correlating their changes with changes in extracranial circulation. While THIe and tHbe generally provided concordant indications, tHbi and THIi exhibited opposite-sign changes in a high percentage of cases (VM: 46%; HV: 31%; HUT: 40%). Moreover, tHbi was correlated with THIi only during HV (P < 0.05), not during VM and HUT, while it correlated with PPG in all three maneuvers (P < 0.01). These results evidence that extracranial circulation may markedly affect BL parameters in a high percentage of cases, even during standard clinical tests. Surface plethysmography at the forehead is suggested as complementary monitoring helpful in the interpretation of cerebral NIRS parameters.     

Effects of compression on muscle tissue oxygenation at the onset of exercise

The effects of compression on gastrocnemius medialis muscle oxygenation and hemodynamics during a short-term dynamic exercise was investigated in a sample of 15 male subjects (mean ± SD; age 25.8 ± 4.9 years; mass 70.6 ± 4.3 kg). Elastic compression sleeves were used to apply multiple levels of compression to the calf muscles during exercise, and noncompressive garments were used for the control condition. Tissue hemoglobin oxygen saturation was measured as the relative "tissue oxygen index" (TOI) with a near-infrared spectrometer. The recovery of TOI during exercise was determined from the slope of oxygenation recovery in a nonoccluded situation. The TOI recovery rate during the first 2 minutes of the exercise was 24% higher (p = 0.042) for the compression condition than for the control condition. A significant correlation (r = 0.61, p = 0.012) between the level of compression and the tissue oxygenation recovery during exercise was observed. Muscle energy use was determined from the rate of decline of TOI immediately upon arterial occlusion during early exercise. Muscle energy use measured during the occluded situation was not significantly influenced by compression. Based on these results, it was concluded that compression induced changes in tissue blood flow and perfusion appear to result in improved oxygenation during short-term exercise. Assuming that increased muscle oxygen availability positively influences performance, compression of muscles may enhance performance especially in sports that require repeated short bouts of exercise.     

Effects of head-down tilt on cerebral blood flow in humans ans rabbits

Changes in cerebral hemodynamics, during and after head down tilt (HDT), were examined by means of transcranial Doppler technique (TCD) and near infrared spectroscopy (NIRS) in humans, and laser Doppler flowmetry (LDF) in rabbits. Mean cerebral blood flow (CBF) velocity measured by TCD increased during the first 6 h of HDT compared with the pre-HDT value. NIRS experiments demonstrated that brain oxygenation and hemoglobin concentration increased with postural change from upright to supine. These results suggest that exposure to HDT increases CBF during the early phase of HDT in humans. In rabbits anesthetized with alpha chloralose, on the other hand, 45 degrees HDT did not change CBF significantly in the parietal cortex during 1 h after the onset of HDT. The discrepancy may be explained by the difference in species, tilt angle, or the brain region where CBF has been measured.     

Muscle oxygenation and pulmonary gas exchange kinetics during cycling exercise on-transitions in humans.

Near-infrared spectroscopy (NIRS) was utilized to gain insights into the kinetics of oxidative metabolism during exercise transitions. Ten untrained young men were tested on a cycle ergometer during transitions from unloaded pedaling to 5 min of constant-load exercise below (VT) the ventilatory threshold. Vastus lateralis oxygenation was determined by NIRS, and pulmonary O2 uptake (Vo --> Vo2) was determined breath-by-breath. Changes in deoxygenated hemoglobin + myoglobin concentration Delta[deoxy(Hb + Mb)] were taken as a muscle oxygenation index. At the transition, [Delta[deoxy(Hb + Mb)]] was unmodified [time delay (TD)] for 8.9 +/- 0.5 s at VT (both significantly different from 0) and then increased, following a monoexponential function [time constant (tau) = 8.5 +/- 0.9 s for VT]. For >VT a slow component of Delta[deoxy(Hb + Mb)] on-kinetics was observed in 9 of 10 subjects after 75.0 +/- 14.0 s of exercise. A significant correlation was described between the mean response time (MRT = TD + tau) of the primary component of Delta[deoxy(Hb + Mb)] on-kinetics and the tau of the primary component of the pulmonary Vo2 on-kinetics. The constant muscle oxygenation during the initial phase of the on-transition indicates a tight coupling between increases in O2 delivery and O2 utilization. The lack of a drop in muscle oxygenation at the transition suggests adequacy of O2 availability in relation to needs.     

Dietary nitrate improves muscle but not cerebral oxygenation status during exercise in hypoxia

Exercise tolerance is impaired in hypoxia, and it has recently been shown that dietary nitrate supplementation can reduce the oxygen (O(2)) cost of muscle contractions. Therefore, we investigated the effect of dietary nitrate supplementation on arterial, muscle, and cerebral oxygenation status, symptoms of acute mountain sickness (AMS), and exercise tolerance at simulated 5,000 m altitude. Fifteen young, healthy volunteers participated in three experimental sessions according to a crossover study design. From 6 days prior to each session, subjects received either beetroot (BR) juice delivering 0.07 mmol nitrate/kg body wt/day or a control drink (CON). One session was in normoxia with CON (NOR(CON)); the two other sessions were in hypoxia (11% O(2)), with either CON (HYP(CON)) or BR (HYP(BR)). Subjects first cycled for 20 min at 45% of peak O(2) consumption (VO(2)peak; EX(45%)) and thereafter, performed a maximal incremental exercise test (EX(max)). Whole-body VO(2), arterial O(2) saturation (%SpO(2)) via pulsoximetry, and tissue oxygenation index of both muscle (TOI(M)) and cerebral (TOI(C)) tissue by near-infrared spectroscopy were measured. Hypoxia per se substantially reduced VO(2)peak, %SpO(2), TOI(M), and TOI(C) (NOR(CON) vs. HYP(CON), P < 0.05). Compared with HYP(CON), VO(2) at rest and during EX(45%) was lower in HYP(BR) (P < 0.05), whereas %SpO(2) was higher (P < 0.05). TOI(M) was ～4-5% higher in HYP(BR) than in HYP(CON) both at rest and during EX(45%) and EX(max) (P < 0.05). TOI(C) as well as the incidence of AMS symptoms were similar between HYP(CON) and HYP(BR) at any time. Hypoxia reduced time to exhaustion in EX(max) by 36% (P < 0.05), but this ergolytic effect was partly negated by BR (+5%, P < 0.05). Short-term dietary nitrate supplementation improves arterial and muscle oxygenation status but not cerebral oxygenation status during exercise in severe hypoxia. This is associated with improved exercise tolerance against the background of a similar incidence of AMS.     

The repeated-bout effect: influence on biceps brachii oxygenation and myoelectrical activity

This study investigated biceps brachii oxygenation and myoelectrical activity during and following maximal eccentric exercise to better understand the repeated-bout effect. Ten men performed two bouts of eccentric exercise (ECC1, ECC2), consisting of 10 sets of 6 maximal lengthening contractions of the elbow flexors separated by 4 wk. Tissue oxygenation index minimum amplitude (TOI(min)), mean and maximum total hemoglobin volume by near-infrared spectroscopy, torque, and surface electromyography root mean square (EMG(RMS)) during exercise were compared between ECC1 and ECC2. Changes in maximal voluntary isometric contraction (MVC) torque, range of motion, plasma creatine kinase activity, muscle soreness, TOI(min), and EMG(RMS) during sustained (10-s) and 30-repeated isometric contraction tasks at 30% (same absolute force) and 100% MVC (same relative force) for 4 days postexercise were compared between ECC1 and ECC2. No significant differences between ECC1 and ECC2 were evident for changes in torque, TOI(min), mean total hemoglobin volume, maximum total hemoglobin volume, and EMG(RMS) during exercise. Smaller (P < 0.05) changes and faster recovery of muscle damage markers were evident following ECC2 than ECC1. During 30% MVC tasks, TOI(min) did not change, but EMG(RMS) increased 1-4 days following ECC1 and ECC2. During 100% MVC tasks, EMG(RMS) did not change, but torque and TOI(min) decreased 1-4 days following ECC1 and ECC2. TOI(min) during 100% MVC tasks and EMG(RMS) during 30% MVC tasks recovered faster (P < 0.05) following ECC2 than ECC1. We conclude that the repeated-bout effect cannot be explained by altered muscle activation or metabolic/hemodynamic changes, and the faster recovery in muscle oxygenation and activation was mainly due to faster recovery of force.     

Noninvasive evaluation of skeletal muscle mitochondrial capacity with near-infrared spectroscopy: correcting for blood volume changes

Near-infrared spectroscopy (NIRS) is a well-known method used to measure muscle oxygenation and hemodynamics in vivo. The application of arterial occlusions allows for the assessment of muscle oxygen consumption (mVo(2)) using NIRS. The aim of this study was to measure skeletal muscle mitochondrial capacity using blood volume-corrected NIRS signals that represent oxygenated hemoglobin/myoglobin (O(2)Hb) and deoxygenated hemoglobin/myoglobin (HHb). We also assessed the reliability and reproducibility of NIRS measurements of resting oxygen consumption and mitochondrial capacity. Twenty-four subjects, including four with chronic spinal cord injury, were tested using either the vastus lateralis or gastrocnemius muscles. Ten healthy, able-bodied subjects were tested on two occasions within a period of 7 days to assess the reliability and reproducibility. NIRS signals were corrected for blood volume changes using three different methods. Resting oxygen consumption had a mean coefficient of variation (CV) of 2.4% (range 1-32%). The recovery of oxygen consumption (mVo(2)) after electrical stimulation at 4 Hz was fit to an exponential curve, which represents mitochondrial capacity. The time constant for the recovery of mVo(2) was reproducible with a mean CV of 10% (range 1-22%) only when correcting for blood volume changes. We also examined the effects of adipose tissue thickness on measurements of mVo(2). We found the mVo(2) measurements using absolute units to be influenced by adipose tissue thickness (ATT), and this relationship was removed when an ischemic calibration was performed, supporting its use to compare mVo(2) between individuals of varying ATT. In conclusion, in vivo oxidative capacity can be assessed using blood volume-corrected NIRS signals with a high degree of reliability and reproducibility.     

Measurement of cerebral blood volume using near-infrared spectroscopy and indocyanine green elimination.

Methods for measuring cerebral blood volume (CBV) have traditionally used radioisotopes. More recently, near-infrared spectroscopy (NIRS) has been used to measure CBV by using a technique involving O(2) desaturation of cerebral tissue, where the observed change in the concentration of oxygenated hemoglobin is a marker of the volume of blood contained within the brain. A new integration method employing NIRS is described by using indocyanine green (ICG) as the intravascular marker. After bolus injection, concentration-time integrals of cerebral tissue ICG concentration ([ICG](tissue)) measured by NIRS are compared with corresponding integrals of the cerebral blood ICG concentrations ([ICG](blood)) estimated by high-performance liquid chromatography of peripheral blood samples with allowance for cerebral-to-large-vessel hematocrit ratio. It is shown that CBV = integral [ICG]tissue/[ICG]blood. Measurements in 10 adult volunteers gave a mean value of 1.1 +/- 0.39 (SD) ml/100 g illuminated tissue. This result, although lower than previous NIRS estimations, is consistent with the long extracerebral path of light in the adult head. Scaling of results is required to take into account this component of the optical pathlength.     

Functional near infrared spectroscopy using spatially resolved data to account for tissue scattering: A numerical study and arm‐cuff experiment

Functional Near‐Infrared Spectroscopy (fNIRS) aims to recover changes in tissue optical parameters relating to tissue hemodynamics, to infer functional information in biological tissue. A widely‐used application of fNIRS relies on continuous wave (CW) methodology that utilizes multiple distance measurements on human head for study of brain health. The typical method used is spatially resolved spectroscopy (SRS), which is shown to recover tissue oxygenation index (TOI) based on gradient of light intensity measured between two detectors. However, this methodology does not account for tissue scattering which is often assumed. A new parameter recovery algorithm is developed, which directly recovers both the scattering parameter and scaled chromophore concentrations and hence TOI from the measured gradient of light‐attenuation at multiple wavelengths. It is shown through simulations that in comparison to conventional SRS which estimates cerebral TOI values with an error of ±12.3%, the proposed method provides more accurate estimate of TOI exhibiting an error of ±5.7% without any prior assumptions of tissue scatter, and can be easily implemented within CW fNIRS systems. Using an arm‐cuff experiment, the obtained TOI using the proposed method is shown to provide a higher and more realistic value as compared to utilizing any prior assumptions of tissue scatter.     

A modular NIRS system for clinical measurement of impaired skeletal muscle oxygenation.

Near-infrared spectrometry (NIRS) is a well-known method used to measure in vivo tissue oxygenation and hemodynamics. This method is used to derive relative measures of hemoglobin (Hb) + myoglobin (Mb) oxygenation and total Hb (tHb) accumulation from measurements of optical attenuation at discrete wavelengths. We present the design and validation of a new NIRS oxygenation analyzer for the measurement of muscle oxygenation kinetics. This design optimizes optical sensitivity and detector wavelength flexibility while minimizing component and construction costs. Using in vitro validations, we demonstrate 1) general optical linearity, 2) system stability, and 3) measurement accuracy for isolated Hb. Using in vivo validations, we demonstrate 1) expected oxygenation changes during ischemia and reactive hyperemia, 2) expected oxygenation changes during muscle exercise, 3) a close correlation between changes in oxyhemoglobin and oxymyoglobin and changes in deoxyhemoglobin and deoxymyoglobin and limb volume by venous occlusion plethysmography, and 4) a minimal contribution from movement artifact on the detected signals. We also demonstrate the ability of this system to detect abnormal patterns of tissue oxygenation in a well-characterized patient with a deficiency of skeletal muscle coenzyme Q(10). We conclude that this is a valid system design for the precise, accurate, and sensitive detection of changes in bulk skeletal muscle oxygenation, can be constructed economically, and can be used diagnostically in patients with disorders of skeletal muscle energy metabolism.     

Muscle oxygenation dynamics in response to electrical stimulation as measured with near‐infrared spectroscopy: A pilot study

Neuromuscular electrical stimulation (NMES) is used for preventing muscle atrophy and improving muscle strength in patients and healthy people. However, the current intensity of NMES is usually set at a level that causes the stimulated muscles to contract. This typically causes pain. Quantifying the instantaneous changes in muscle microcirculation and metabolism during NMES before muscle contraction occurs is crucial, because it enables the current intensity to be optimally tuned, thereby reducing the NMES‐induced muscle pain and fatigue. We applied near‐infrared spectroscopy (NIRS) to measure instantaneous tissue oxygenation and deoxygenation changes in 43 healthy young adults during NMES at 10, 15, 20, 25, 30, and 35 mA. Having been stabilized at the NIRS signal baseline, the tissue oxygenation and total hemoglobin concentration increased immediately after stimulation in a dose‐dependent manner (P < 0.05) until stimulation was stopped at the level causing muscle contraction without pain. Tissue deoxygenation appeared relatively unchanged during NMES. We conclude that NIRS can be used to determine the optimal NMES current intensity by monitoring oxygenation changes.      

Effects of assuming constant optical scattering on measurements of muscle oxygenation by near-infrared spectroscopy during exercise.

The aim of this study was to examine the effects of assuming constant reduced scattering coefficient (mu'(s)) on the muscle oxygenation response to incremental exercise and its recovery kinetics. Fifteen subjects (age: 24 +/- 5 yr) underwent incremental cycling exercise. Frequency domain near-infrared spectroscopy (NIRS) was used to estimate deoxyhemoglobin concentration {[deoxy(Hb+Mb)]} (where Mb is myoglobin), oxyhemoglobin concentration {[oxy(Hb+Mb)]}, total Hb concentration (Total[Hb+Mb]), and tissue O(2) saturation (Sti(O(2))), incorporating both continuous measurements of mu'(s) and assuming constant mu'(s). When measuring mu'(s), we observed significant changes in NIRS variables at peak work rate Delta[deoxy(Hb+Mb)] (15.0 +/- 7.8 microM), Delta[oxy(Hb+Mb)] (-4.8 +/- 5.8 microM), DeltaTotal[Hb+Mb] (10.9 +/- 8.4 microM), and DeltaSti(O(2))(-11.8 +/- 4.1%). Assuming constant mu'(s) resulted in greater (P < 0.01 vs. measured mu'(s)) changes in the NIRS variables at peak work rate, where Delta[deoxy(Hb+Mb)] = 24.5 +/- 15.6 microM, Delta[oxy(Hb+Mb)] = -9.7 +/- 8.2 microM, DeltaTotal[Hb+Mb] = 14.8 +/- 8.7 microM, and DeltaSti(O(2))= -18.7 +/- 8.4%. Regarding the recovery kinetics, the large 95% confidence intervals (CI) for the difference between those determine measuring mu'(s) and assuming constant mu'(s) suggested poor agreement between methods. For the mean response time (MRT), which describes the overall kinetics, the 95% confidence intervals were MRT - [deoxy(Hb+Mb)] = 26.7 s; MRT - [oxy(Hb+Mb)] = 11.8 s, and MRT - Sti(O(2))= 11.8 s. In conclusion, mu'(s) changed from light to peak exercise. Furthermore, assuming a constant mu'(s) led to an overestimation of the changes in NIRS variables during exercise and distortion of the recovery kinetics.     

Impairments in microvascular reactivity are related to organ failure in human sepsis

Severe sepsis is a systemic inflammatory response to infection resulting in acute organ dysfunction. Vascular perfusion abnormalities are implicated in the pathology of organ failure, but studies of microvascular function in human sepsis are limited. We hypothesized that impaired microvascular responses to reactive hyperemia lead to impaired oxygen delivery relative to the needs of tissue and that these impairments would be associated with organ failure in sepsis. We studied 24 severe sepsis subjects 24 h after recognition of organ dysfunction; 15 healthy subjects served as controls. Near-infrared spectroscopy (NIRS) was used to measure tissue 1) microvascular hemoglobin signal strength and 2) oxygen saturation of microvascular hemoglobin (StO2). Both values were measured in thenar skeletal muscle before and after 5 min of forearm stagnant ischemia. At baseline, skeletal muscle microvascular hemoglobin was lower in septic than control subjects. Microvascular hemoglobin increased during reactive hyperemia in both groups, but less so in sepsis. StO2 at baseline and throughout ischemia was similar between the two groups; however, the rate of tissue oxygen consumption was significantly slower in septic subjects than in controls. The rate of increase in StO2 during reactive hyperemia was significantly slower in septic subjects than in controls; this impairment was accentuated in those with more organ failure. We conclude that organ dysfunction in severe sepsis is associated with dysregulation of microvascular oxygen balance. NIRS measurements of skeletal muscle microvascular perfusion and reactivity may provide important information about sepsis and serve as endpoints in future therapeutic interventions aimed at improving the microcirculation.     

A comparison of cerebral activity in the prefrontal region between young adults and the elderly while driving

The purpose of this study is to investigate the difference of cerebral activity in the prefrontal region between young adults and elderly subjects during driving. The procedure of the experiment was explained to the subjects and informed consent was obtained. Fourteen young male adults (21.6+/-0.76 yrs), seven elderly males (69.9+/-4.91 yrs), and seven elderly females (66.6+/-6.02 yrs) volunteered as subjects for the experiments. Non-invasive measurement of regional cerebral activity was estimated by measuring the deoxygenated hemoglobin, oxygenated hemoglobin, and total hemoglobin of both sides of the prefrontal region using near-infrared spectroscopy (NIRS) and time-resolved spectroscopy (TRS). The distance to the vehicle in front, speed, and braking were recorded and the behavior of the drivers was obtained using a CCD camera and video recorder. Temperature and relative humidity in the experimental car were 23-25 degrees Centigrade and 30-40%RH respectively. Background noise in the car was 50-65 dB (A). The less experienced young adults display a greater increase in prefrontal cerebral activity than do the experienced young adults during driving. Prefrontal cerebral activity in elderly subjects is lower than that in young adults at rest and shows little variation compared with young adults during driving. Less experienced young adults and elderly males display similar behavior patterns in driving, such as not observing the door mirror carefully when changing lane. The less experienced young adults are considered to be less adapted to driving. It is possible to evaluate adaptability for driving by means of measuring cerebral hemodynamic changes while driving.     

Cerebral oxygenation is highly sensitive to blood pressure variability in sick preterm infants

Objectives

The significance of blood pressure variability (BPV) for cerebral oxygenation in extremely preterm infants has not been explored, though BPV may well be associated with end organ injury. We hypothesized that increased BPV in sick preterm infants, by exceeding the cerebral autoregulatory capacity, is associated with cerebral oxygenation changes which closely follow the blood pressure fluctuations. We assessed the autoregulatory capacity in the early postnatal period, by determining the correlation between BPV (mmHg²) and coherence of mean arterial blood pressure (MABP mmHg) and cerebral oxygenation (tissue oxygenation index, TOI %).

Study Design

Thirty-two preterm infants of mean gestational age of 26.3 (±1.5) weeks were studied on the first 3 postnatal days. Spectral analysis (Coherence and transfer-function gain analysis) was used to calculate coherence of MABP and TOI; BPV was quantified using power spectral density of MABP.

Results

Overall, maximum Coherence showed a trend for positive correlation with BPV (n = 32, p = 0.06). Infants identified as clinically unstable with documented brain injury (n = 7) had high Coherence values at low BPV. Separate analysis of stable infants (excluding the 7 critically ill infants) revealed a significant association between maximum Coherence and BPV (n = 25, p = 0.006).

Conclusions

Fluctuation in cerebral oxygenation is closely associated with increased BPV in preterm infants undergoing intensive care. Moreover, in the critically sick preterm infant, blood pressure-dependent variations in cerebral oxygenation occur even with relatively lower BPV, suggesting they have severely impaired autoregulation, and placing them at greater vulnerability to cerebral injury arising from blood pressure fluctuations.     

Magnetic-stimulation-related physiological artifacts in hemodynamic near-infrared spectroscopy signals

Hemodynamic responses evoked by transcranial magnetic stimulation (TMS) can be measured with near-infrared spectroscopy (NIRS). This study demonstrates that cerebral neuronal activity is not their sole contributor. We compared bilateral NIRS responses following brain stimulation to those from the shoulders evoked by shoulder stimulation and contrasted them with changes in circulatory parameters. The left primary motor cortex of ten subjects was stimulated with 8-s repetitive TMS trains at 0.5, 1, and 2 Hz at an intensity of 75% of the resting motor threshold. Hemoglobin concentration changes were measured with NIRS on the stimulated and contralateral hemispheres. The photoplethysmograph (PPG) amplitude and heart rate were recorded as well. The left shoulder of ten other subjects was stimulated with the same protocol while the hemoglobin concentration changes in both shoulders were measured. In addition to PPG amplitude and heart rate, the pulse transit time was recorded. The brain stimulation reduced the total hemoglobin concentration (HbT) on the stimulated and contralateral hemispheres. The shoulder stimulation reduced HbT on the stimulated shoulder but increased it contralaterally. The waveforms of the HbT responses on the stimulated hemisphere and shoulder correlated strongly with each other (r = 0.65–0.87). All circulatory parameters were also affected. The results suggest that the TMS-evoked NIRS signal includes components that do not result directly from cerebral neuronal activity. These components arise from local effects of TMS on the vasculature. Also global circulatory effects due to arousal may affect the responses. Thus, studies involving TMS-evoked NIRS responses should be carefully controlled for physiological artifacts and effective artifact removal methods are needed to draw inferences about TMS-evoked brain activity.     

Hemodynamic consequences of rapid changes in posture in humans.

Tolerance to +G(z) gravitational stress is reduced when +G(z) stress is preceded by exposure to hypogravity (fraction, 0, or negative G(z)). For example, there is an exaggerated fall in eye-level arterial pressure (ELAP) early on during +G(z) stress (head-up tilt; HUT) when this stress is immediately preceded by -G(z) stress (head-down tilt; HDT). The aims of the present study were to characterize the hemodynamic consequences of brief HDT on subsequent HUT and to test the hypothesis that an elevation in leg vascular conductance induced by -G(z) stress contributes to the exaggerated fall in ELAP. Young healthy subjects (n = 3 men and 4 women) were subjected to 30 s of 30 degrees HUT from a horizontal position and to 30 s of 30 degrees HUT when HUT was immediately preceded by 20 s of -15 degrees HDT. Four bouts of HDT-HUT were alternated between five bouts of HUT in a counterbalanced designed to minimize possible time effects of repeated exposure to gravitational stress. One minute was allowed for recovery between tilts. Brief exposure to HDT elicited an exaggerated fall in ELAP during the first seconds of the subsequent HUT (-17.9 +/- 1.4 mmHg) compared with HUT alone (-12.4 +/- 1.2 mmHg, P <0.05) despite a greater rise in stroke volume (Doppler ultrasound) and cardiac output over this brief time period in the HDT-HUT trials compared with the HUT trials (thereafter stroke volume fell under both conditions). The greater fall in ELAP was associated with an exaggerated increase in leg blood flow (femoral artery Doppler ultrasound) and was therefore largely (70%) attributable to an exaggerated rise in estimated leg vascular conductance, confirming our hypotheses. Thus brief exposure to -G(z) stress leads to an exaggerated fall in ELAP during subsequent HUT, owing to an exaggerated increase in estimated leg vascular conductance.     

The intramuscular contribution to the slow oxygen uptake kinetics during exercise in chronic heart failure is related to the severity of the condition

The mechanism for slow pulmonary O(2) uptake (Vo(2)) kinetics in patients with chronic heart failure (CHF) is unclear but may be due to limitations in the intramuscular control of O(2) utilization or O(2) delivery. Recent evidence of a transient overshoot in microvascular deoxygenation supports the latter. Prior (or warm-up) exercise can increase O(2) delivery in healthy individuals. We therefore aimed to determine whether prior exercise could increase muscle oxygenation and speed Vo(2) kinetics during exercise in CHF. Fifteen men with CHF (New York Heart Association I-III) due to left ventricular systolic dysfunction performed two 6-min moderate-intensity exercise transitions (bouts 1 and 2, separated by 6 min of rest) from rest to 90% of lactate threshold on a cycle ergometer. Vo(2) was measured using a turbine and a mass spectrometer, and muscle tissue oxygenation index (TOI) was determined by near-infrared spectroscopy. Prior exercise increased resting TOI by 5.3 ± 2.4% (P = 0.001), attenuated the deoxygenation overshoot (-3.9 ± 3.6 vs. -2.0 ± 1.4%, P = 0.011), and speeded the Vo(2) time constant (τVo(2); 49 ± 19 vs. 41 ± 16 s, P = 0.003). Resting TOI was correlated to τVo(2) before (R(2) = 0.51, P = 0.014) and after (R(2) = 0.36, P = 0.051) warm-up exercise. However, the mean response time of TOI was speeded between bouts in half of the patients (26 ± 8 vs. 20 ± 8 s) and slowed in the remainder (32 ± 11 vs. 44 ± 16 s), the latter group having worse New York Heart Association scores (P = 0.042) and slower Vo(2) kinetics (P = 0.001). These data indicate that prior moderate-intensity exercise improves muscle oxygenation and speeds Vo(2) kinetics in CHF. The most severely limited patients, however, appear to have an intramuscular pathology that limits Vo(2) kinetics during moderate exercise.