Effects of parabolic flight and spaceflight on the endocannabinoid system in humans

The endocannabinoid system (ECS) plays an important role in the regulation of physiological functions, from stress and memory regulation to vegetative control and immunity. The ECS is considered a central and peripheral stress response system to emotional or physical challenges and acts through endocannabinoids (ECs), which bind to their receptors inducing subsequent effecting mechanisms. In our studies, the ECS responses have been assessed through blood concentrations of the ECs anandamide and 2-arachidonoylglycerol. In parallel, saliva cortisol was determined and the degree of perceived stress was quantified by questionnaires. This report summarizes the reactivity of the ECS in humans subjected to brief periods of kinetic stress and weightlessness during parabolic flights and to prolonged stress exposure during life onboard the International Space Station (ISS). Both conditions resulted in a significant increase in circulating ECs. Under the acute stress during parabolic flights, individuals who showed no evidence of motion sickness were in low-stress conditions and had a significant increase of plasma ECs. In contrast, highly stressed individuals with severe motion sickness had an absent EC response and a massive increase in hypothalamic-pituitary-adrenal axis activity. Likewise, chronic but well-tolerated exposure to weightlessness and emotional and environmental stressors on the ISS for 6 months resulted in a sustained increase in EC blood concentrations, which returned to baseline values after the cosmonauts' return. These preliminary results suggest that complex environmental stressors result in an increase of circulating ECs and that enhanced EC signaling is probably required for adaptation and tolerance under stressful conditions

Motion sickness, stress and the endocannabinoid system

A substantial number of individuals are at risk for the development of motion sickness induced nausea and vomiting (N&V) during road, air or sea travel. Motion sickness can be extremely stressful but the neurobiologic mechanisms leading to motion sickness are not clear. The endocannabinoid system (ECS) represents an important neuromodulator of stress and N&V. Inhibitory effects of the ECS on N&V are mediated by endocannabinoid-receptor activation

Assessment of coronary sinus anatomy between normal and insufficient mitral valves by multi-slice computertomography for mitral annuloplasty device implantation

Introduction: Latest techniques enable positioning of devices into the coronary sinus (CS) for mitral valve (MV) annuloplasty. We evaluate the feasibility of non-invasive assessment to determine CS anatomy and its relation to MV annulus and coronary arteries by multi-slice CT (MSCT) in normal and insufficient MV. Methods: Fifty patients (33 males, 17 females, age 67±11 years) were studied retrospectively by 64-MSCT scans for anatomical criteria regarding CS and its relation to MV annulus and circumflex artery (CX). We included 24 patients with severe mitral insufficiency and 26 with no MV disease. Diameter of MV, of proximal and distal ostium of CS, length and volume of CS, angle between anterior interventricular vein (AIV) and CS, caliber change of CX before, under/over and after CS were analysed. Different anatomical correlations were demonstrated: distance of MV annulus to CS, CX to CS. Results: Diameter of proximal CS ostium was significantly larger in insufficient MV compared to normal MV (11±2.8mm vs 9.9±2.5mm; p<0.024). CS was significantly longer in patients with insufficient MV (125.4±17mm vs 108.9±18mm; p<0.003) with also significant differences in volume of CS (p<0.039). Significant difference in annulus diameter, 46.1±6mm (insufficient MV) versus 39.5±7.5mm, p<0.004 was observed. Angle CS-AIV was 103.5±29° (range 52°-144°) in insufficient valves versus 118.2±24.5° (range 73°-166°) in normal valves with a tendency to higher angles in normal valves (p=0.06). Distance of MV annulus to CS measured 16±4.1/14.2±3.6mm (insufficient/normal MV) without significant difference between groups. In 15 patients CX ran under CS. Eighty-four percent of these patients (13/15) show a decrease in CS caliber in the area of intersection. In 14 patients CS ran over and in one patient the diameter of the CS at intersecting region was smaller. In 16 patients no direct point of contact was visible, in five patients CX to CS positioning was not evaluable. Conclusion: There is a significant anatomic difference between normal and insufficient MV, which might be the basis for any interventional approaches through the CS. Exact measurements of all structures and its anatomic correlations are possible with MSCT, which allows pre-interventional plannin

Quantification of myocardial blood flow with 82Rb positron emission tomography: clinical validation with 15O-water

Purpose: Quantification of myocardial blood flow (MBF) with generator-produced 82Rb is an attractive alternative for centres without an on-site cyclotron. Our aim was to validate 82Rb-measured MBF in relation to that measured using 15O-water, as a tracer 100% of which can be extracted from the circulation even at high flow rates, in healthy control subject and patients with mild coronary artery disease (CAD). Methods: MBF was measured at rest and during adenosine-induced hyperaemia with 82Rb and 15O-water PET in 33 participants (22 control subjects, aged 30 ± 13years; 11 CAD patients without transmural infarction, aged 60 ± 13years). A one-tissue compartment 82Rb model with ventricular spillover correction was used. The 82Rb flow-dependent extraction rate was derived from 15O-water measurements in a subset of 11 control subjects. Myocardial flow reserve (MFR) was defined as the hyperaemic/rest MBF. Pearson's correlation r, Bland-Altman 95% limits of agreement (LoA), and Lin's concordance correlation ρ c (measuring both precision and accuracy) were used. Results: Over the entire MBF range (0.66-4.7ml/min/g), concordance was excellent for MBF (r = 0.90, [82Rb-15O-water] mean difference ± SD = 0.04 ± 0.66ml/min/g, LoA = −1.26 to 1.33ml/min/g, ρ c = 0.88) and MFR (range 1.79-5.81, r = 0.83, mean difference = 0.14 ± 0.58, LoA = −0.99 to 1.28, ρ c = 0.82). Hyperaemic MBF was reduced in CAD patients compared with the subset of 11 control subjects (2.53 ± 0.74 vs. 3.62 ± 0.68ml/min/g, p = 0.002, for 15O-water; 2.53 ± 1.01 vs. 3.82 ± 1.21ml/min/g, p = 0.013, for 82Rb) and this was paralleled by a lower MFR (2.65 ± 0.62 vs. 3.79 ± 0.98, p = 0.004, for 15O-water; 2.85 ± 0.91 vs. 3.88 ± 0.91, p = 0.012, for 82Rb). Myocardial perfusion was homogeneous in 1,114 of 1,122 segments (99.3%) and there were no differences in MBF among the coronary artery territories (p > 0.31). Conclusion: Quantification of MBF with 82Rb with a newly derived correction for the nonlinear extraction function was validated against MBF measured using 15O-water in control subjects and patients with mild CAD, where it was found to be accurate at high flow rates. 82Rb-derived MBF estimates seem robust for clinical research, advancing a step further towards its implementation in clinical routin

Non-invasive assessment of coronary artery disease with CT coronary angiography and SPECT: a novel dose-saving fast-track algorithm

Purpose: To validate a new low-dose and rapid stepwise individualized algorithm for non-invasive assessment of ischemic coronary artery disease by sequential use of prospectively ECG-triggered low-dose CT coronary angiography (CTCA) and low-dose single-photon emission computed tomography myocardial perfusion imaging (SPECT-MPI). Methods: Forty patients referred for elective invasive coronary angiography (CA) were prospectively enrolled to undergo a comprehensive non-invasive evaluation with low-dose CTCA and a dose-reduced stress/rest SPECT-MPI scan (using dedicated reconstruction algorithms for low count scans). The following algorithm was reviewed: CTCA first, followed by a stress-only MPI if a coronary stenosis (≥ 50% diameter narrowing) or equivocal findings were observed. Only abnormal stress MPI scans were followed by rest MPI. The accuracy of the individualized algorithm to predict coronary revascularization and its mean effective radiation dose were assessed. Results: CTCA documented CAD in 18 and equivocal findings in two patients, thus, requiring additional stress MPI scans. Of these, 16 were abnormal, therefore requiring a rest MPI scan, revealing ischemia in 15 patients. Sensitivity, specificity, negative and positive predictive value, and accuracy of the individualized algorithm for predicting coronary revascularization was 93.3%, 96.0%, 96.0%, 93.3% and 95.0% on a per-patient base. The mean effective radiation dose was significantly lower for the individualized (4.8 ± 3.4mSv) versus the comprehensive method (8.1 ± 1.5mSv) resulting in a total population radiation dose reduction of 132.6mSv. Conclusion: This new individualized low-dose algorithm allows rapid and accurate prediction of invasive CA findings and of treatment decision with minimized radiation dos

Assessment of myocardial perfusion by dynamic O-15-labeled water PET imaging: Validation of a new fast factor analysis

Background: Factor analysis (FA) is an established method for separating myocardium from blood pool by use of oxygen 15-labeled water and positron emission tomography for analyzing myocardial blood flow (MBF). Conventional FA methods generating images from sinograms (sinoFA) are time-consuming, whereas FA can be performed on the reconstructed images (reconFA) in a fraction of time. We validated the MBF values obtained by reconFA versus sinoFA. Methods and Results: In 23 volunteers (mean age, 26.6±3.4 years) MBF was calculated from sinoFA and reconFA and blindly reanalyzed 1 month later by the same observer. Intraobserver agreement and reconFA-versus-sinoFA agreement were assessed according to Bland and Altman (BA). Reproducibility proved excellent for global sinoFA (r=0.968; P<.001; BA limits, −0.617 to 0.676 mL·min−1·g−1) and slightly superior for reconFA (r=0.979; P<.001; BA limits, −0.538 to 0.558 mL·min−1·g−1), with wider limits of agreement for segmental MBF from sinoFA (r=0.777; P<.001; BA limits, −1.676 to 1.656 mL·min−1·g−1) and reconFA (r=0.844; P<.001; BA limits, −1.999 to 1.992 mL·min−1·g−1). In addition, sinoFA and reconFA showed excellent correlation (r=0.975, P<.001) and agreement (BA limits, −0.528 to 0.648 mL·min−1·g−1) for global and segmental values (r=0.955; P<.001; BA limits, −1.371 to 1.491 mL·min−1·g−1). Conclusions: Use of reconFA allows rapid and reliable quantitative MBF assessment with O-15-labeled wate

Determinants of vessel contrast in BMI-adapted low dose CT coronary angiography with prospective ECG-triggering

We evaluated the determinants of vessel contrast in prospectively ECG-triggered CT coronary angiography (CTCA). Seventy patients underwent low-dose CTCA using Body Mass Index (BMI)-adapted tube parameters and a fixed contrast material bolus. Contrast to noise ratio (CNR) was calculated from contrast (between coronaries and perivascular tissue) and image noise (standard deviation of aortic attenuation). Cardiac output (CO) was calculated from gated 99mTc-tetrofosmin-SPECT. Mean radiation dose was 2.13±0.69mSv. Image noise was not affected by BMI (r=0.1, P=0.36), while CNR was inversely related to body surface area (BSA) (r=−0.5, P<0.001) and CO (r=−0.45, P<0.001). After successfully overcoming the impact of BMI on image noise by adapting tube parameters, CNR mainly depends on coronary vessel contrast. The latter reflects the dilution of the contrast material by blood volume and CO, which are both correlated to BSA. Therefore, BSA adapted contrast administration may help to compensate for this effec

Coronary calcium score scans for attenuation correction of quantitative PET/CT 13N-ammonia myocardial perfusion imaging

Purpose: The aim of this study was to evaluate whether ECG-triggered coronary calcium scoring (CCS) scans can be used for attenuation correction (AC) to quantify myocardial blood flow (MBF) and coronary flow reserve (CFR) assessed by PET/CT with 13N-ammonia. Methods: Thirty-five consecutive patients underwent a 13N-ammonia PET/CT scan at rest and during standard adenosine stress. MBF values were calculated using AC maps obtained from the ECG-triggered CCS scan during inspiration and validated against MBF values calculated using standard non-gated transmission scans for AC. CFR was calculated as the ratio of hyperaemic over resting MBF. In all 35 consecutive patients intraobserver variability was assessed by blinded repeat analysis for both AC methods. Results: There was an excellent correlation between CT AC and CCS for global MBF values at rest (n = 35, r = 0.94, p < 0.001) and during stress (n = 35, r = 0.97, p < 0.001) with narrow Bland-Altman (BA) limits of agreement (−0.21 to 0.10ml/min per g and −0.41 to 0.30ml/min per g) as well as for global CFR (n = 35, r = 0.96, p < 0.001, BA −0.27 to 0.34). The excellent correlation was preserved on the segmental MBF analysis for both rest and stress (n = 1190, r = 0.93, p < 0.001, BA −0.60 to 0.50) and for CFR (n = 595, r = 0.87, p < 0.001, BA −0.71 to 0.74). In addition, reproducibility proved excellent for global CFR by CT AC (n = 35, r = 0.91, p < 0.001, BA −0.42-0.58) and CCS scans (n = 35, r = 0.94, p < 0.001, BA −0.34-0.45). Conclusion: Use of attenuation maps from CCS scans allows accurate quantitative MBF and CFR assessment with 13N-ammonia PET/C