Response of Ventricular Repolarization to Simulated Microgravity Measured by Periodic Repolarization Dynamics Using Phase-Rectified Signal Averaging

Head-Down Bed Rest (HDBR) microgravity simulation induces cardiovascular deconditioning, including effects on ventricular repolarization. The index of Periodic Repolarization Dynamics (PRD) was developed to quantify low-frequency oscillations of cardiac repolarization. In this study, PRD was quantified by Phase Rectified Signal Averaging (PRDPRSA) and Continuous Wavelet Transform (PRDCWT) methods. PRD was analyzed in ECGs from 22 volunteers at rest and during orthostatic Tilt-Table Test (TTT) performed before and after -6° 60-days HDBR. Significant correlation was found between PRD measured by PRSA and CWT (Pearson''s ¿ = 0.93, p < 10-54 and Kendall''s t = 0.79 p < 10-38). A highly significant increase was found when PRDPRSA values were measured at POST-HDBR with respect to PRE-HDBR in the tilt phase: 1.40 [1.10] deg and 0.97 [0.90] deg (median [IQR]), p = 0.008, respectively. PRDPRSA also increased significantly in the tilt phase with respect to baseline, both at POST-HDBR (0.90 [0.57] deg, p = 0.003) and at PRE-HDBR (0.75 [0.45] deg, p = 0.011). PRD, either measured with PRSA or with CWT, is able to measure changes in ventricular repolarization induced by microgravity simulation as well as following sympathetic provocation

Evaluation of Cardiac Circadian Rhythm Deconditioning Induced by 5-to-60 Days of Head-Down Bed Rest

Head-down tilt (HDT) bed rest elicits changes in cardiac circadian rhythms, generating possible adverse health outcomes such as increased arrhythmic risk. Our aim was to study the impact of HDT duration on the circadian rhythms of heart beat (RR) and ventricular repolarization (QTend) duration intervals from 24-h Holter ECG recordings acquired in 63 subjects during six different HDT bed rest campaigns of different duration (two 5-day, two 21-day, and two 60-day). Circadian rhythms of RR and QTend intervals series were evaluated by Cosinor analysis, resulting in a value of midline (MESOR), oscillation amplitude (OA) and acrophase (f). In addition, the QTc (with Bazett correction) was computed, and day-time, night-time, maximum and minimum RR, QTend and QTc intervals were calculated. Statistical analysis was conducted, comparing: (1) the effects at 5 (HDT5), 21 (HDT21) and 58 (HDT58) days of HDT with baseline (PRE); (2) trends in recovery period at post-HDT epochs (R) in 5-day, 21-day, and 60-day HDT separately vs. PRE; (3) differences at R + 0 due to bed rest duration; (4) changes between the last HDT acquisition and the respective R + 0 in 5-day, 21-day, and 60-day HDT. During HDT, major changes were observed at HDT5, with increased RR and QTend intervals’ MESOR, mostly related to day-time lengthening and increased minima, while the QTc shortened. Afterward, a progressive trend toward baseline values was observed with HDT progression. Additionally, the f anticipated, and the OA was reduced during HDT, decreasing system’s ability to react to incoming stimuli. Consequently, the restoration of the orthostatic position elicited the shortening of RR and QTend intervals together with QTc prolongation, notwithstanding the period spent in HDT. However, the magnitude of post-HDT changes, as well as the difference between the last HDT day and R + 0, showed a trend to increase with increasing HDT duration, and 5/7 days were not sufficient for recovering after 60-day HDT. Additionally, the f postponed and the OA significantly increased at R + 0 compared to PRE after 5-day and 60-day HDT, possibly increasing the arrhythmic risk. These results provide evidence that continuous monitoring of astronauts’ circadian rhythms, and further investigations on possible measures for counteracting the observed modifications, will be key for future missions including long periods of weightlessness and gravity transitions, for preserving astronauts’ health and mission success

Selective beat averaging to evaluate ventricular repolarization adaptation to deconditioning after 5 days of head-down bed rest

The study of QT/RR relationship is important for the clinical evaluation of possible risk of ventricular tachyarrhythmia. Our aim was to assess the effects of 5-days of head-down (-6 degrees) bed-rest (HDBR) on ventricular repolarization. High fidelity 12-leads Holter ECG was acquired before (PRE), the last day of HDBR (HDT5), and five days after its conclusion (POST). X, Y, Z leads were derived (inverse Dower matrix) and vectorcardiogram computed. Selective beat averaging applied to the night period resulted in averages preceded by the same stable heart rate (for each 10 msec bin amplitude, in the range 900-1200 msec). For each template (i.e., one for each bin), T-wave maximum amplitude (Tmax), T wave area, R-Tapex and R-Tend were computed. Results (in 8 male volunteers) showed that, compared to PRE, at HDT5 both R-Tapex and R-Tend resulted significantly shortened (-5% and -3%, respectively), together with a decrease in T-wave area (-7%), while Tmax was unchanged. At POST, duration parameters showed a trend towards their control values (-1.5% and -3%, respectively) while amplitude parameters resulted restored. Despite the short-term BR, cardiac adaptation to deconditioning affected ventricular repolarization during the night period. © 2012 CCAL

Mitral Valve Patient-Specific Finite Element Modeling from Cardiac MRI: Application to an Annuloplasty Procedure

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AORTIC VESSEL WALL PROPERTIES DURING 60 DAYS STRICT HEAD DOWN TILT BEDREST - PRELIMINARY RESULTS OF AGBRESA

Background Changes in large artery properties including increased arterial compliance and increased carotid artery stiffness have been described after space flight. Altered vascular structure, which heralds cardiovascular risk, and reversible changes in vascular function could contribute to the response. Compared with previous studies, which did not reproduce these findings, AGBRESA applied strict -6° head-down bedrest (HDT) mimicking chronic cephalad fluid shifts in space. In this study, we assessed aortic vessel wall properties using state-of-the art imaging methods and pulse wave analysis and tested for possible protective effects of artificial gravity training. Material and Methods We present preliminary data from 12 healthy subjects (8 men, 4 women) obtained during baseline data collection 9-6 days before bedrest (BDC, supine position) and towards the end of two months head down tilt bedrest (MRI on day 56 and echocardiography on day 60 of HDT). Subjects were assigned to 30 minutes per day continuous short arm centrifugation (cAG), 6 times for 5 minutes interval short arm centrifugation, iAG), or a control group (ctr). We assessed aortic pulse wave velocity using oscillometric upper arm and thigh cuffs (PWV-2C, CardioCube, AIT, Vienna, Austria) and 4D-flow cardiac velocity encoded phase contrast magnetic resonance imaging (PWV-4D-MRI). We also measured area, area changes, and distensibility (AoD) of the ascending aorta by 2D-phase contrast cardiac MRI and arterial compliance (Ca) using transthoracic echocardiography. Results Mean aortic area increased in all subjects after 60 days head down tilt bedrest (5.3±0.7 vs. 5.8±0.7 cm², p<0.05). Stroke volume decreased from 94±13 to 84±10 ml (p<0.05) and pulse pressure from 56±11 to 46±9 mmHg (p<0.05) in part through reductions in stroke volume. The figure illustrates individual data on aortic properties (red diamonds = women). In contrast to the more consistent changes in aortic area, stroke volume, and pulse pressure, aortic distensibility, compliance, and pulse wave velocity responses show substantial inter-individual variability. Conclusion The important finding of our study is that 60 days strict head down bedrest elicit consistent changes in ascending aortic area, pulse pressure, and stroke volume. The resulting changes in vascular loading conditions likely confound vascular function measurements, both, in head down bedrest studies and in space

From Kepler&#8217;s conjecture and fcc lattice to modelling of crowding in living matter

Up to now, sphere packing has been investigated without any reference to living matter. This study focuses on the void space (VS) of sphere packing to mimic the extracellular spaces of living tissues. It was inspired by the importance of the extracellular matrix, the vehicle of micro and macromolecules involved in cell metabolism, intercellular communication and drug delivery. The analysis of sphere packing evidenced that in uniform random packing VS is about 1.9 times greater than in the face centered cubic (fcc) lattice (thus being very close to the 1.9 volume ratio of the cube to the sphere). This datum is a good reference for cell packing in vivo. The disproportionate increase of VS per sphere in loose packing in vitro is analyzed having in mind the variability in volume and composition of the interstitial spaces in vivo and cell trafficking. Arrangements of lymphocytes mimicking a two-dimensional hexagonal pattern and dense packing of disks generated by numerical procedures, are described in 7 \u3bcm-thick haematoxylin and eosin-stained histological slices from a human lymph node. In narrow tubes simulating roundish cells arranged in limited compartments of the interstice, sphere packing is characterized by noticeable increases of VS. The VS of this packing in vitro is compatible with variability in volume and composition of the interstitial spaces and with cell trafficking in vivo. This paper stresses that in mammalian tissues and organs cells can be packed quite more densely than spheres in the fcc lattice. As to pathology, attention is focused: (i) on overcrowding of cell organelles in some diseases, (ii) on shrinking or swelling of high amplitude, whose opposite effects are to concentrate or dilute intracellular structures and crowding of macromolecules, and (iii) on neoplastic tissues