Heart functional and structural compendium of cardiosplenic and cardiorenal networks in acute and chronic heart failure pathology.

Abstract

Heart failure (HF) secondary to myocardial infarction (MI) is linked to kidney complications that comprise cellular, structural, functional, and survival indicators. However, HF research is focused on left ventricular (LV) pathology. Here, we determined comprehensive functional analysis of the LV using echocardiography in transition from acute heart failure (AHF) to progressive chronic heart failure (CHF) pathology and developed 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 mo old, n = 50). Temporal LV function analysis indicated that fractional shortening and strain are reduced from day 1 to day 5 in AHF and sustained to advance to CHF from day 28 to day 56 compared with naïve control mice ( n = 6). During the 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 effective approaches to study either cardiac repair or cardiac pathology. NEW & NOTEWORTHY The present compendium shows irreversible ventricular dysfunction as assessed by temporal echocardiography while histological and structural measurements of the spleen and kidney added a novel direction to study cardiosplenic and cardiorenal networks in heart failure pathology. Therefore, the consideration of systems biology and integrative approach is essential to develop novel treatments.