Targeting Sarcoplasmic Reticulum Ca 2+ Uptake to Improve Heart Failure

][3] The causality is more difficult to prove at this late time point. 4et, the observed reduction in the Ca 2ϩ available for myofilament activation and reduced Ca 2ϩ reuptake in the sarcoplasmic reticulum (SR) are obvious targets to improve myocyte contraction and relaxation and, thus, cardiac pump function.Early pharmacotherapy mimicked adrenergic stimulation, the physiological boost of contraction and relaxation, by raising cAMP.Although this worked well, and still does, for acute treatment, the long-term results showed an increase in mortality.Alternative therapy to enhance myofilament sensitivity seems a safer alternative. 5,6any animal models have been designed to reproduce heart failure in humans allowing study of myocyte remodeling at different stages of disease.The most extensively studied are genetic predisposition (the cardiomyopathic hamster), pressure overload (hypertensive models, aortic banding), myocardial infarction (MI), and tachycardia pacing (in dog or rabbit).Except for genetic model, obvious discrepancies with human disease are the fast time course of the disease and the relative lack of complexity, as, for example, the absence of atherosclerosis in most models of MI.Nevertheless these models have been very useful to demonstrate that very often in vivo cardiac dysfunction paralleled changes in Ca 2ϩ handling, suggesting causality.