Systolic and diastolic dysfunction of the left ventricle (LV) is a hallmark of most cardiac diseases. In vivo assessment of heart function in animal models, particularly mice, is essential to refining our understanding of cardiovascular disease processes. Ultrasound echocardiography has emerged as a powerful, noninvasive tool to serially monitor cardiac performance and map the progression of heart dysfunction in murine injury models. This review covers current applications of small animal echocardiography, as well as emerging technologies that improve evaluation of LV function. In particular, we describe speckle-tracking imaging-based regional LV analysis, a recent advancement in murine echocardiography with proven clinical utility. This sensitive measure enables an early detection of subtle myocardial defects before global dysfunction in genetically engineered and rodent surgical injury models. Novel visualization technologies that allow in-depth phenotypic assessment of small animal models, including perfusion imaging and fetal echocardiography, are also discussed. As imaging capabilities continue to improve, murine echocardiography will remain a critical component of the investigator's armamentarium in translating animal data to enhanced clinical treatment of cardiovascular diseases. murine echocardiography; systolic and diastolic function; speckle-tracking imaging; strain analysis; heart failure THIS ARTICLE is part of a collection on Assessing Cardiovascular Function in Mice: New Developments and Methods. Other articles appearing in this collection, as well as a full archive of all collections, can be found online at http://ajpheart.physiology.org/.Rodents are invaluable models for cardiovascular research, in part because of the extensive knowledge of their genome, homogeneity of study population, reproducible pathological phenotypes, and relative ease of creating genetically modified models. Surgical techniques that induce myocardial overload, infarction, and dysfunction in mice and rats have enabled a reliable identification and assessment of key physiological, molecular, and biochemical mechanisms of cardiovascular diseases (43). With the use of noninvasive imaging tools such as ultrasound echocardiography, cardiovascular evaluation of rodents has further led to the translational development of new diagnostic techniques and therapeutic strategies to predict and prevent cardiovascular disease complications in humans (82).Echocardiography remains a gold standard for a reliable assessment of cardiovascular structure and function in humans (19). The technology's allure lies primarily in its portability, relative affordability, widespread availability, noninvasive nature, and rapid real-time imaging capabilities. With advancements in clinical echocardiography, the technicalities and conceptual framework of the methodology and equipment have been extended from humans to small animals. Ultrasound imaging greatly facilitates the evaluation of cardiac function in transgenic animals, as well as surgically induced ...

Cyclic nucleotide phosphodiesterase 1C (PDE1C) represents a major phosphodiesterase activity in human myocardium, but its function in the heart remains unknown. Using genetic and pharmacological approaches, we studied the expression, regulation, function, and underlying mechanisms of PDE1C in the pathogenesis of cardiac remodeling and dysfunction. PDE1C expression is up-regulated in mouse and human failing hearts and is highly expressed in cardiac myocytes but not in fibroblasts. In adult mouse cardiac myocytes, PDE1C deficiency or inhibition attenuated myocyte death and apoptosis, which was largely dependent on cyclic AMP/PKA and PI3K/AKT signaling. PDE1C deficiency also attenuated cardiac myocyte hypertrophy in a PKA-dependent manner. Conditioned medium taken from PDE1C-deficient cardiac myocytes attenuated TGF-β-stimulated cardiac fibroblast activation through a mechanism involving the crosstalk between cardiac myocytes and fibroblasts. In vivo, cardiac remodeling and dysfunction induced by transverse aortic constriction, including myocardial hypertrophy, apoptosis, cardiac fibrosis, and loss of contractile function, were significantly attenuated in PDE1C-knockout mice relative to wild-type mice. These results indicate that PDE1C activation plays a causative role in pathological cardiac remodeling and dysfunction. Given the continued development of highly specific PDE1 inhibitors and the high expression level of PDE1C in the human heart, our findings could have considerable therapeutic significance.cyclic nucleotide | phosphodiesterase | cardiac remodeling | heart failure

Our data support the hypothesis that measures of heart rate power spectra are inversely related and negatively correlated to severity of illness and outcome in critically ill and injured children. The phenomenon of decomplexification of physiologic dynamics may have important clinical implications in critical illness and injury.

Background Platelets have a pathophysiologic role in the ischemic microvascular environment of acute coronary syndromes (ACS). Compared to platelet activation in normal healthy conditions, less attention is given to mechanisms of platelet activation in diseased states. Platelet function and mechanisms of activation in ischemic and reactive oxygen species (ROS) rich environments may not be the same as in normal healthy conditions. Extracellular Regulated Protein Kinase 5 (ERK5) is a Mitogen Activated Protein Kinase (MAPK) family member activated in hypoxic, ROS rich environments, and in response to receptor signaling mechanisms. Prior studies suggest a protective effect of ERK5 in endothelial and myocardial cells following ischemia. We present evidence that platelets express ERK5 and platelet ERK5 has an adverse effect on platelet activation via selective receptor-dependent and receptor-independent ROS mediated mechanisms in ischemic myocardium. Methods and Results Using isolated human platelets and a mouse model of myocardial infarction (MI), we found that platelet ERK5 is activated post-MI and platelet specific ERK5−/− mice have less platelet activation, reduced MI size, and improved post-MI heart function. Furthermore, the expression of downstream ERK5 regulated proteins is reduced in ERK5−/− platelets post-MI. Conclusions ERK5 functions as a platelet activator in ischemic conditions and platelet ERK5 maintains the expression of some platelet proteins following MI, leading to infarct expansion. This demonstrates that platelet function in normal healthy conditions is different from platelet function in chronic ischemic and inflammatory conditions. Platelet ERK5 may be a target for acute therapeutic intervention in the thrombotic and inflammatory post-MI environment.