Heart Functional and Structural Compendium of Cardiosplenic and Cardiorenal Networks in Acute and Chronic Heart Failure Pathology.

Heart failure (HF) secondary to myocardial infarction (MI) is linked to kidney complications that comprise cellular, structural, functional, and survival indicators. However, the HF research is focused on left ventricle (LV) pathology. Here, we determined the comprehensive functional analysis of LV using echocardiography in transition from acute HF (AHF) to progressive CHF pathology and develop a histological compendium of the cardiosplenic and cardiorenal networks in pathological remodeling. In surgically-induced MI using permanent coronary ligation, the LV dysfunction is pronounced, with myocardium necrosis, wall-thinning and 20-30% LV rupture events that indicated AHF and CHF pathological remodeling in C57BL/6 male mice (2-4 months old; n=50). Temporal LV function analysis indicated that fractional shortening and strain is reduced from day 1 to day 5 in AHF and sustained to advance to CHF from day 28 to 56 compared to naïve control (n=6). During transition of AHF (day 1 to day 5) to advanced CHF (day 28 to day 56), histological and cellular changes in the spleen were definite, with bimodal inflammatory responses in kidney inflammatory biomarkers. Likewise, there was a unidirectional, progressive and irreversible deposition of compact collagen in the LV along with dynamic changes in the cardiosplenic and cardiorenal networks post-MI. The renal histology and injury markers suggested that cardiac-injury triggers irreversible dysregulation that actively alters the cardiosplenic and cardiorenal networks. In summary, the novel strategies or pathways that modulate comprehensive cardiosplenic and cardiorenal networks in AHF and CHF would be an effective approach to study either cardiac repair or cardiac pathology.