• Quantitative multiplex immunohistochemistry employing 23 antibodies was used to identify the immune cells present in the left ventricle 2 weeks after ischemia-reperfusion. • Two therapeutics (ISP and HJ-02), administered on days 3-10 after ischemia-reperfusion, restored sympathetic innervation throughout the left ventricle and decreased arrhythmia susceptibility. • Treatment with ISP and HJ-02 shifted the immune response from inflammatory to reparative, with fewer pro-inflammatory (M1-like) macrophages and increased numbers of regulatory T cells and reparative (M2-like) macrophages in reinnervated hearts. • HJ-02 stimulated a significantly greater shift from pro-inflammatory to reparative cell types compared with ISP, which coincided with decreased infarct size and normal cardiac output and ejection fraction. • Neither ISP nor HJ-02 altered macrophage phenotypes in cultured peritoneal macrophages, which suggested that reinnervation contributes to the M1 to M2 shift in vivo.

Aging is associated with a decline in cardiac function. Exercise intervention has been suggested as a way to improve this decrement. Age-related decline in cardiac function is associated with decreases in fatty acid oxidation, mitochondrial function and AMP-activated protein kinase (AMPK) activity. The molecular mechanisms involved with age-related changes in mitochondrial function and substrate metabolism are poorly understood. We determined gene expression differences in hearts of Young (6 mo), Old (33 mo), and old exercise trained (Old + EXE) (34 mo) FBN rats, using Qiagen PCR arrays for Glucose, Fatty acid, and Mitochondrial metabolism. Old rats demonstrated decreased (p < 0.05) expression for key genes in fatty acid oxidation, mitochondrial function, and AMPK signaling. There were no differences in the expression of genes involved in glucose metabolism with age. These gene expression changes occurred prior to altered protein translation as we found no differences in the protein content of peroxisome proliferator activated receptor gamma, coactivators 1 alpha (PGC-1α), peroxisome proliferator activated receptor alpha (PPARα), and AMPKα2 between young and old hearts. Four months of exercise training did not attenuate the decline in the gene expression in aged hearts. Despite this lack of change in gene expression, exercise-trained rats demonstrated increased exercise capacity compared to their sedentary counterparts. Taken together, our results show that differential expression of genes associated with fatty acid metabolism, AMPK signaling and mitochondrial function are superfluous and decrease in the aging heart which may play a role in age-related declines in fatty acid oxidation, AMPK activity and mitochondrial function in the heart.

With an aging population, the incidence of both ischemic heart disease and strokes have become the most prevalent diseases globally. These diseases have similar risk factors, such as hypertension, diabetes, and smoking. However, there is also evidence of a relationship between the heart and the brain, referred to as the heart–brain axis. In this relationship, dysfunction of either organs can lead to injury to the other. There are several proposed physiologies to explain this relationship. These theories usually involve vascular, neuromodulatory, and inflammatory processes; however, few articles have explored and compared these different mechanisms of interaction between the heart and brain. A better understanding of the heart–brain axis can inform physicians of current and future treatment and preventive care options in heart and brain pathologies. The relationship between the brain and heart depends on inflammation, vascular anatomy and function, and neuromodulation. The pathways connecting these organs often become injured or dysfunctional when a major pathology, such as a myocardial infarction or stroke, occurs. This leads to long-term impacts on the patient’s overall health and risk for future disease. This study summarizes the current research involved in the heart–brain axis, relates these interactions to different diseases, and proposes future research in the field of neurocardiology. Conditions of the brain and heart are some of the most prevalent diseases. Through understanding the connection between these two organs, we can help inform patients and physicians of novel therapeutics for these pathologies.