Each heartbeat is initiated by cyclic spontaneous depolarization of cardiomyocytes in the sinus node forming the primary natural pacemaker. In patients with end-stage renal disease undergoing hemodialysis, it was recently shown that the heart rate drops to very low values before they suffer from sudden cardiac death with an unexplained high incidence. We hypothesize that the electrolyte changes commonly occurring in these patients affect sinus node beating rate and could be responsible for severe bradycardia. To test this hypothesis, we extended the Fabbri et al. computational model of human sinus node cells to account for the dynamic intracellular balance of ion concentrations. Using this model, we systematically tested the effect of altered extracellular potassium, calcium, and sodium concentrations. Although sodium changes had negligible (0.15 bpm/mM) and potassium changes mild effects (8 bpm/mM), calcium changes markedly affected the beating rate (46 bpm/mM ionized calcium without autonomic control). This pronounced bradycardic effect of hypocalcemia was mediated primarily by I attenuation due to reduced driving force, particularly during late depolarization. This, in turn, caused secondary reduction of calcium concentration in the intracellular compartments and subsequent attenuation of inward I and reduction of intracellular sodium. Our in silico findings are complemented and substantiated by an empirical database study comprising 22,501 pairs of blood samples and in vivo heart rate measurements in hemodialysis patients and healthy individuals. A reduction of extracellular calcium was correlated with a decrease of heartrate by 9.9 bpm/mM total serum calcium (p < 0.001) with intact autonomic control in the cross-sectional population. In conclusion, we present mechanistic in silico and empirical in vivo data supporting the so far neglected but experimentally testable and potentially important mechanism of hypocalcemia-induced bradycardia and asystole, potentially responsible for the highly increased and so far unexplained risk of sudden cardiac death in the hemodialysis patient population.
The paper is addressed to detect the parameters of a sphere-center coordinates and radius based on a stack of CT slices. It is proposing a new hierarchical Hough transform approach. In the first step, all slices are taken into consideration sequentially and a 2D accumulator array is used to obtain the coordinates (x"0,y"0), the projecting value of the sphere center into every X-Y-plane. In this step, also a new type of 2D Hough transform for circle or circular detection is proposed based on an effective point filtering. In the second step, the radii of the circles in the different slices are obtained using 1D accumulator arrays. In the last step, the coordinate z"0 and the radius R of the sphere are acquired using a 2D planar Hough transform based on the correlation between the radii of circles, the coordinates z of the slice and the sphere radius. The hierarchical Hough transform is applied to analyze the structure of femoral head of human hip joints. Compared to the established Hough transform techniques for 3D object detection, the hierarchical Hough transform reduces storage space and calculation time significantly and it has a good robustness to noise in the images.