Abstract: The present teachings provide compounds of Formulae I and II: and pharmaceutically acceptable salts, hydrates, complexes, esters, and prodrugs thereof, wherein R1, R1?, R2, R2?, R3, R3?, and X are as defined herein. The present teachings also provide methods of making the compounds of formulae I and II, and methods of treating RyR-associated conditions, disorders, and diseases that include administering a therapeutically effective amount of a compound of formula I or II to a subject in need thereof. In addition, the present teachings relate to methods of reducing the open probability of a ryanodine receptor, and methods of reducing Ca2+ release across a ryanodine receptor (e.g., into the cytoplasm of a cell), by contacting a compound of formula I or II with a ryanodine receptor.

Abstract: Methods and apparatus for determining a cardiac parameter from cardiovascular pressure signals including arterial blood pressure (ABP) and the photoplethysmographic signal to quantify the degree of amplitude modulation due to respiration and predict fluid responsiveness are disclosed. Disclosed embodiments include a method for assessing fluid responsiveness implemented in a digital computer with one or more processors comprising: (a) measuring a cardiovascular signal, and (b) computing a dynamic index predictive of fluid responsiveness from said cardiovascular signal using a nonlinear state space estimator. According to one particular embodiment, and without limitation, the nonlinear state space estimator is based on a model for cardiovascular signals such as arterial blood pressure or plethysmogram signals, and employs a marginalized particle filter to estimate a dynamic index predictive of fluid responsiveness that is substantially equivalent to a variation in pulse pressure of said cardiovascular signal.

Abstract: Disclosed embodiments of the invention include a method, system, and apparatus to monitor cardiovascular signals such as arterial blood pressure (ABP), pulse oximetry (POX), and intracranial pressure (ICP). The system can be used to calculate and monitor useful clinical information such as heart rate, respiratory rate, pulse pressure variation (PPV), harmonic phases, pulse morphology, and for artifact removal. The method uses a statistical state-space model of cardiovascular signals and a generalized Kalman filter (EKF) to simultaneously estimate and track the cardiovascular parameters of interest such as the cardiac fundamental frequency and higher harmonics, respiratory fundamental frequency and higher harmonics, cardiac component harmonic amplitudes and phases, respiratory component harmonic amplitudes and phases, and PPV.