A Quantitative Investigation of Selected Reactions in the Fibrinolytic Cascade

Previous work has shown that thrombin activatable fibrinolysis inhibitor (TAFI) was unable to prolong lysis of purified clots in the presence of Lys-plasminogen (Lys-Pg), indicating a possible mechanism for fibrinolysis to circumvent prolongation mediated by activated TAFI (TAFIa). Therefore, the effects of TAFIa on Lys-Pg activation and Lys-plasmin (Lys-Pn) inhibition by antiplasmin (AP) were quantitatively investigated using a fluorescently labeled recombinant Pg mutant which does not produce active Pn. High molecular weight fibrin degradation products (HMW-FDPs), a soluble fibrin surrogate that models Pn modified fibrin, treated with TAFIa decreased the catalytic efficiency (kcat/Km) of 5IAF-Glu-Pg cleavage by 417-fold and of 5IAF-Lys-Pg cleavage by 55-fold. A previously devised intact clot system was used to measure the apparent second order rate constant (k2) for Pn inhibition by AP over time. While TAFIa was able to abolish the protection associated with Pn modified fibrin in clots formed with Glu-Pg, it was not able to abolish the protection in clots formed with Lys-Pg. However, TAFIa was still able to prolong the lysis of clots formed with Lys-Pg. TAFIa prolongs clot lysis by removing the positive feedback loop for Pn generation. The effect of TAFIa modification of the HMW-FDPs on the rate of tissue type plasminogen activator (tPA) inhibition by plasminogen activator inhibitor type 1 (PAI-1) was investigated using a previously devised end point assay. HMW-FDPs decreased the k2 for tPA inhibition rate by 3-fold. Thus, HMW-FDPs protect tPA from PAI-1. TAFIa treatment of the HMW-FDPs resulted in no change in protection. Vitronectin also did not appreciably affect tPA inhibition by PAI-1. Pg, in conjunction with HMW-FDPs, decreased the k2 for tPA inhibition by 30-fold. Hence, Pg, when bound to HMW-FDPs, protects tPA by an additional 10-fold. TAFIa treatment of the HMW-FDPs completely removed this additional protection provided by Pg. In conclusion, an additional mechanism was identified whereby TAFIa can prolong clot lysis by increasing the rate of tPA inhibition by PAI-1 by eliminating the protective effects of Pn-modified fibrin and Pg. Because TAFIa can suppress Lys-Pg activation but cannot attenuate Lys-Pn inhibition by AP, the Glu- to Lys-Pg/Pn conversion is able to act as a fibrinolytic switch to ultimately lyse the clot.

An investigation of lower limb joint powers as a predictive measure of countermovement vertical jump height.

Measuring and tracking athletic performance is crucial to an athlete’s development and the countermovement vertical jump is often used to measure athletic performance, particularly lower limb power. The linear power developed in the lower limb is estimated through jump height. However, the relationship between angular power, produced by the joints of the lower limb, and jump height is not well understood. This study examined the contributions of the kinetic value of angular power, and its kinematic component, angular velocity, of the lower limb joints to jump height in the countermovement vertical jump. Kinematic and kinetic data were gathered from twenty varsity-level basketball and volleyball athletes as they performed six maximal effort jumps in four arm swing conditions: no-arm involvement, single-non-dominant arm swing, single-dominant arm swing, and two-arm swing. The displacement of the whole body centre of mass, peak joint powers, peak angular velocity, and locations of the peaks as a percentage of the jump’s takeoff period, were computed. Linear regressions assessed the relationship of the variables to jump height. Results demonstrated that knee peak power (p = 0.001, ß = 0.363, r = 0.363), its location within takeoff period (p = 0.023, ß = -0.256, r = 0.256), and peak knee peak angular velocity (p = 0.005, ß = 0.310, r = 0.310) were moderately linked to increased jump height. Additionally, the location, within the takeoff period, of the peak angular velocities of the hip (p = 0.003, ß = -0.318, r = 0.419) and ankle (p = 0.011, ß = 0.270, r = 0.419) were positively linked to jump height. These results highlight the importance of training the velocity and timing of joint motion beyond traditional power training protocols as well as the importance of further investigation into appropriate testing protocol that is sensitive to the contributions by individual joints in maximal effort jumping.