Background and Purpose-The pressure reactivity index (PRx) describes cerebral vessel reactivity by correlation of slow waves of intracranial pressure (ICP) and arterial blood pressure. In theory, slow changes in the relative total hemoglobin (rTHb) measured by near-infrared spectroscopy are caused by the same blood volume changes that cause slow waves of ICP. Our objective was to develop a new index of vascular reactivity, the hemoglobin volume index (HVx), which is a low-frequency correlation of arterial blood pressure and rTHb measured with near-infrared spectroscopy. Methods-Gradual hypotension was induced in piglets while cortical laser-Doppler flux was monitored. ICP was monitored, and rTHb was measured continuously using reflectance near-infrared spectroscopy. The HVx was recorded as a moving linear correlation between slow waves (20 to 300 seconds) of arterial blood pressure and rTHb.

Barth syndrome (BTHS) is a mitochondrial myopathy characterized by reports of exercise intolerance. We sought to determine if 1) BTHS leads to abnormalities of skeletal muscle O(2) extraction/utilization and 2) exercise intolerance in BTHS is related to impaired O(2) extraction/utilization, impaired cardiac function, or both. Participants with BTHS (age: 17 ± 5 yr, n = 15) and control participants (age: 13 ± 4 yr, n = 9) underwent graded exercise testing on a cycle ergometer with continuous ECG and metabolic measurements. Echocardiography was performed at rest and at peak exercise. Near-infrared spectroscopy of the vastus lateralis muscle was continuously recorded for measurements of skeletal muscle O(2) extraction. Adjusting for age, peak O(2) consumption (16.5 ± 4.0 vs. 39.5 ± 12.3 ml·kg(-1)·min(-1), P < 0.001) and peak work rate (58 ± 19 vs. 166 ± 60 W, P < 0.001) were significantly lower in BTHS than control participants. The percent increase from rest to peak exercise in ejection fraction (BTHS: 3 ± 10 vs. control: 19 ± 4%, P < 0.01) was blunted in BTHS compared with control participants. The muscle tissue O(2) saturation change from rest to peak exercise was paradoxically opposite (BTHS: 8 ± 16 vs. control: -5 ± 9, P < 0.01), and the deoxyhemoglobin change was blunted (BTHS: 0 ± 12 vs. control: 10 ± 8, P < 0.09) in BTHS compared with control participants, indicating impaired skeletal muscle extraction in BTHS. In conclusion, severe exercise intolerance in BTHS is due to both cardiac and skeletal muscle impairments that are consistent with cardiac and skeletal mitochondrial myopathy. These findings provide further insight to the pathophysiology of BTHS.

The CAS neonatal NIRS system determines absolute regional brain tissue oxygen saturation (SnO2) and brain true venous oxygen saturation (SnvO2) non-invasively. Since NIRS-interrogated tissue contains both arterial and venous blood from arterioles, venules, and capillaries, SnO2 is a mixed oxygen saturation parameter, having values between arterial oxygen saturation (SaO2) and cerebral venous oxygen saturation (SvO2). To determine a reference for SnO2, the relative contribution of SvO2 to SaO2 drawn from a brain venous site vs. systemic SaO2 is approximately 70:30 (SvO2:SaO2). If the relationship of the relative average contribution of SvO2 and SaO2 is known and does not change to a large degree, then NIRS true venous oxygen saturation, SnvO2, can be determined non-invasively using SnO2 along with SaO2 from a pulse oximeter.

We describe the validation methodology for the NIRS based FORE-SIGHT ELITE® (CAS Medical Systems, Inc., Branford, CT, USA) tissue oximeter for cerebral and somatic tissue oxygen saturation (StO2) measurements for adult subjects submitted to the United States Food and Drug Administration (FDA) to obtain clearance for clinical use. This validation methodology evolved from a history of NIRS validations in the literature and FDA recommended use of Deming regression and bootstrapping statistical validation methods. For cerebral validation, forehead cerebral StO2 measurements were compared to a weighted 70:30 reference (REF CXB) of co-oximeter internal jugular venous and arterial blood saturation of healthy adult subjects during a controlled hypoxia sequence, with a sensor placed on the forehead. For somatic validation, somatic StO2 measurements were compared to a weighted 70:30 reference (REF CXS) of co-oximetry central venous and arterial saturation values following a similar protocol, with sensors place on the flank, quadriceps muscle, and calf muscle. With informed consent, 25 subjects successfully completed the cerebral validation study. The bias and precision (1 SD) of cerebral StO2 compared to REF CXB was −0.14 ± 3.07%. With informed consent, 24 subjects successfully completed the somatic validation study. The bias and precision of somatic StO2 compared to REF CXS was 0.04 ± 4.22% from the average of flank, quadriceps, and calf StO2 measurements to best represent the global whole body REF CXS. The NIRS validation methods presented potentially provide a reliable means to test NIRS monitors and qualify them for clinical use.

Background: Barth syndrome (BTHS) is a rare X-linked disorder that is characterized by mitochondrial abnormalities, cardio-skeletal myopathy, exercise intolerance, and premature mortality. The effect on endurance exercise training on exercise tolerance, cardio-skeletal function, and quality of life in BTHS is unknown.Methods: Four young adults (23 AE 5 years, n ¼ 4) with BTHS participated in a 12-week, supervised, individualized endurance exercise training program. Exercise training was performed on a cycle ergometer for 30-45 0 three times per week at a moderate intensity level.Exercise tolerance was measured by graded exercise testing and peak oxygen consumption, heart function via two-dimensional and M-mode echocardiography, skeletal muscle function by near-infrared spectroscopy, and quality of life through the Minnesota Living with Heart Failure questionnaire.Results: There were no adverse events during exercise testing or training for any participant. Peak oxygen consumption modestly (~5%) improved in three or four participants. Mean quality of life questions regarding dyspnea and side effects from medications significantly improved following exercise training. Mean resting heart function or skeletal muscle oxygen extraction during exercise did not improve after exercise training.Conclusion: Endurance exercise training is safe and appears to modestly improve peak exercise tolerance and certain measures of quality of life in young adults with BTHS. However, compared to improvements resulting from endurance exercise training seen in other non-BTHS mitochondrial myopathies and heart failure, these improvements appear blunted. Further research into the most beneficial mode, intensity and frequency of exercise training in BTHS is warranted.Barth syndrome (BTHS) is an X-linked disorder that results in cardio-skeletal myopathy, heart failure, fatigue, chronic/ cyclic neutropenia, growth delay, and premature mortality (Barth et al. 1983). The full scope of the pathological and clinical manifestations of BTHS is not fully understood, but involves a tafazzin gene defect that results in cardiolipin deficiency and severe mitochondrial dysfunction. BTHSassociated mitochondrial dysfunction is assumed to mediate the cardio-skeletal myopathy seen in the majority of those with BTHS (Spencer et al. 2006).

Anesthetic exposure during pregnancy is viewed as a relatively routine medical practice. However, recent rodent studies have suggested that common anesthetic agents can damage the developing brain. Here we assessed this claim in a higher order species by exposing previously instrumented near-term pregnant sheep at gestational day 122 (+/-1) to a combination of midazolam, sodium thiopental, and isoflurane at clinically relevant doses and means of anesthetic delivery (i.e., active ventilation). Four hours of maternal general anesthesia produced an initial increase in fetal systemic oxygenation and a sustained increase in fetal cerebral oxygenation, as determined by in utero near-infrared spectroscopy. Postexposure monitoring failed to identify changes in physiologic status that could be injurious to the fetal brain. Finally, through the histologic assessment of noninstrumented sheep at the same gestational time point, we found no evidence for a direct fetal neuro-toxic effect of our triple-drug regimen. Collectively, these results appear to corroborate the presumed safety of inhalational anesthetic use during pregnancy.

Background Increased Hb concentration accompanying hypoxemia is a compensatory response to maintain tissue oxygen delivery (DO2). Near infrared spectroscopy (NIRS) is used clinically to detect abnormalities in the balance of cerebral DO2 and consumption, including in children with congenital heart disease (CHD). Although NIRS-measured cerebral tissue O2 saturation (ScO2) correlates with SaO2, jugular bulb O2 saturation (SjbO2), and Hb, little data exists on the interplay between these factors and cerebral O2 extraction (COE). This study investigated the associations of ScO2 and ΔSaO2–ScO2 with SaO2 and Hb and verified the normal range of ScO2 in children with CHD. Methods Children undergoing cardiac catheterization for CHD were enrolled in a calibration and validation study of the FORE-SIGHT® NIRS monitor. Two pairs of simultaneous arterial and jugular bulb samples were drawn for co-oximetry, calculation of a reference ScO2 (REF CX), and estimation of COE. Pearson correlation and linear regression were used to determine relationships between O2 saturation parameters and Hb. Data were also analyzed according to diagnostic group defined as acyanotic (SaO2 ≥ 90%) and cyanotic (SaO2 < 90%). Results Of 65 children studied, acceptable jugular bulb samples (SjbO2 absolute difference between samples ≤ 10%) were obtained in 57 (88%). The ΔSaO2–SjbO2, ΔSaO2–ScO2, and ΔSaO2−REF CX were positively correlated with SaO2 and negatively correlated with Hb (all P < 0.001). Although by diagnostic group ScO2 differed statistically (P = 0.002), values in the cyanotic patients were within the range considered normal (69 ± 6%). COE estimated by the difference between arterial and jugular bulb O2 content (ΔCaO2−CjbO2, mL O2/100 mL) was not different for cyanotic and acyanotic patients (P = 0.10), but estimates using ΔSaO2–SjbO2, ΔSaO2–ScO2, or ΔSaO2–ScO2/SaO2 were significantly different between the cyanotic and acyanotic children (P < 0.001). Conclusions Children with adequately compensated chronic hypoxemia appear to have ScO2 values within the normal range. The ΔSaO2–ScO2 is inversely related to Hb, with the implication that in the presence of reduced Hb, particularly if coupled with a decreased cardiac output, the ScO2 can fall to values associated with brain injury in laboratory studies.

Any adverse preterm fetal response to maternal surgery should not be attributed solely to the actions of general anesthesia upon the fetus.