Comparison of clockwise and counterclockwise right atrial flutter using high-resolution mapping and automated velocity measurements.

BACKGROUND: Only few studies have been performed that explore the electrophysiological differences between clockwise (CW) and counterclockwise (CCW) right atrial (RA) cavotricuspid isthmus (CTI)-dependent atrial flutter (AFL) using the high-resolution Rhythmia mapping system. OBJECTIVES: We sought to compare CW and CCW CTI-dependent AFL in pure right AFL patients (pts) using the ultra-high-definition (ultra-HD) Rhythmia mapping system and we mathematically developed a cartography model based on automatic velocity RA measurements to identify electrophysiological AFL specificities. METHODS AND RESULTS: Thirty-three pts were recruited. The mean age was 71 ± 13 years old. The sinus venosus (SV) block line was present in 32/33 of cases (97%) and no significant difference was found between CCW and CW CTI AFL (100% vs. 91%; p = .7). No line was localized in the region of the crista terminalis (CT). A superior gap was present in the posterior line in 14/31 (45.2%) but this was similarly present in CCW AFL, when compared to CW AFL (10/22 [45.5%] vs. 4/10 [40%]; p = .9). When present, the extension of the posterior line of block was observed in 18/31 pts (58%) without significant differences between CCW and CW CI AFL (12/22 [54.5%] vs. 6/10 [60%]; p = .9) The Eustachian ridge line of block was similarly present in both groups (82% [18/22] vs. 45.5% [5/11]; p = .2). The absence of the Eustachian ridge line of block led to significantly slowed velocity in this area (28 ± 10 cm/s; n = 8), and the velocities were similarly altered between both groups (26 ± 10 [4/22] vs. 29.8 ± 11 cm/s [4/11]; p = .6). We created mathematical, three-dimensional RA reconstruction-velocity model measurements. In each block localization, when the block line was absent, velocity was significantly slowed (≤20 cm/s). A systematic slowdown in conduction velocity was observed at the entrance and exit of the CTI in 100% of cases. This alteration to the conduction entrance was localized at the lateral side of the CTI for the CCW AFL and at the septal side of the CTI for CW AFL. The exit-conduction alteration was localized at the CTI septal side for the CCW AFL and at the CTI lateral side for the CW AFL. CONCLUSION: The ultra-HD Rhythmia mapping system confirmed the absence of significant electrophysiological differences between CCW and CW AFL. The mechanistic posterior SV and Eustachian ridge block lines were confirmed in each arrhythmia. A systematic slowing down at the entrance and exit of the CTI was demonstrated in both CCW and CW AFL, but in reverse positions.

Mineral density differences between femoral cortical bone and trabecular bone are not explained by turnover rate alone.

Bone mineral density distributions (BMDDs) are a measurable property of bone tissues that depends strongly on bone remodelling and mineralisation processes. These processes can vary significantly in health and disease and across skeletal sites, so there is high interest in analysing these processes from experimental BMDDs. Here, we propose a rigorous hypothesis-testing approach based on a mathematical model of mineral heterogeneity in bone due to remodelling and mineralisation, to help explain differences observed between the BMDD of human femoral cortical bone and the BMDD of human trabecular bone. Recent BMDD measurements show that femoral cortical bone possesses a higher bone mineral density, but a similar mineral heterogeneity around the mean compared to trabecular bone. By combining this data with the mathematical model, we are able to test whether this difference in BMDD can be explained by (i) differences in turnover rate; (ii) differences in osteoclast resorption behaviour; and (iii) differences in mineralisation kinetics between the two bone types. We find that accounting only for differences in turnover rate is inconsistent with the fact that both BMDDs have a similar spread around the mean, and that accounting for differences in osteoclast resorption behaviour leads to biologically inconsistent bone remodelling patterns. We conclude that the kinetics of mineral accumulation in bone matrix must therefore be different in femoral cortical bone and trabecular bone. Although both cortical and trabecular bone are made up of lamellar bone, the different mineralisation kinetics in the two types of bone point towards more profound structural differences than usually assumed.

Late stages of mineralization and their signature on the bone mineral density distribution.

PURPOSE: Experimental measurements of bone mineral density distributions (BMDDs) enable a determination of secondary mineralization kinetics in bone, but the maximum degree of mineralization and how this maximum is approached remain uncertain. We thus test computationally different hypotheses on late stages of bone mineralization by simulating BMDDs in low-turnover conditions. MATERIALS AND METHODS: An established computational model of the BMDD that accounts for mineralization and remodeling processes was extended to limit mineralization to various maximum calcium capacities of bone. Simulated BMDDs obtained by reducing turnover rate from the reference trabecular BMDD under different assumptions on late stage mineralization kinetics were compared with experimental BMDDs of low-turnover bone. RESULTS: Simulations show that an abrupt stopping of mineralization near a maximum calcium capacity induces a pile-up of minerals in the BMDD statistics that is not observed experimentally. With a smooth decrease of mineralization rate, imposing low maximum calcium capacities helps to match peak location and width of simulated low-turnover BMDDs with peak location and width of experimental BMDDs, but results in a distinctive asymmetric peak shape. No tuning of turnover rate and maximum calcium capacity was able to explain the differences found in experimental BMDDs between trabecular bone (high turnover) and femoral cortical bone (low turnover). CONCLUSIONS: Secondary mineralization in human bone does not stop abruptly, but continues slowly up to a calcium content greater than 30 wt% Ca. The similar mineral heterogeneity seen in trabecular and femoral cortical bones at different peak locations was unexplained by the turnover differences tested.

Towards a cell-based mechanostat theory of bone: the need to account for osteocyte desensitisation and osteocyte replacement.

Bone׳s mechanostat theory describes the adaptation of bone tissues to their mechanical environment. Many experiments have investigated and observed such structural adaptation. However, there is still much uncertainty about how to define the reference mechanical state at which bone structure is adapted and stable. Clinical and experimental observations show that this reference state varies both in space and in time, over a wide range of timescales. We propose here an osteocyte-based mechanostat theory that encodes the mechanical reference state in osteocyte properties. This theory assumes that osteocytes are initially formed adapted to their current local mechanical environment through modulation of their properties. We distinguish two main types of physiological processes by which osteocytes subsequently modify the reference mechanical state at different timescales. One is cell desensitisation, which occurs rapidly and reversibly during an osteocyte׳s lifetime. The other is the replacement of osteocytes during bone remodelling, which occurs over the long timescales of bone turnover. The novelty of this theory is to propose that long-lasting morphological and genotypic osteocyte properties provide a material basis for a long-term mechanical memory of bone that is gradually reset by bone remodelling. We test this theory by simulating long-term mechanical disuse (modelling spinal cord injury), and short-term mechanical loadings (modelling daily exercises) with a mathematical model. The consideration of osteocyte desensitisation and of osteocyte replacement by remodelling is able to capture a number of phenomena and timescales observed during the mechanical adaptation of bone tissues, lending support to this theory.