Sepsis is a common condition encountered by emergency and critical care physicians, with significant costs, both economic and human. Myocardial dysfunction in sepsis is a well-recognized but poorly understood phenomenon. There is an extensive body of literature on this subject, yet results are conflicting and no objective definition of septic cardiomyopathy exists, representing a critical knowledge gap. In this article, we review the pathophysiology of septic cardiomyopathy, covering the effects of key inflammatory mediators on both the heart and the peripheral vasculature, highlighting the interconnectedness of these two systems. We focus on the extant literature on echocardiographic and laboratory assessment of the heart in sepsis, highlighting gaps therein and suggesting avenues for future research. Implications for treatment are briefly discussed. As a result of conflicting data, echocardiographic measures of left ventricular (systolic or diastolic) or right ventricular function cannot currently provide reliable prognostic information in patients with sepsis. Natriuretic peptides and cardiac troponins are of similarly unclear utility. Heterogeneous classification of illness, treatment variability, and lack of formal diagnostic criteria for septic cardiomyopathy contribute to the conflicting results. Development of formal diagnostic criteria, and use thereof in future studies, may help elucidate the link between cardiac performance and outcomes in patients with sepsis.

Global brain ischemia/reperfusion induces neuronal damage in vulnerable brain regions, leading to mitochondrial dysfunction and subsequent neuronal death. Induction of neuronal death is mediated by release of cytochrome c (cyt c) from the mitochondria though a well-characterized increase in outer mitochondrial membrane permeability. However, for cyt c to be released it is first necessary for cyt c to be liberated from the cristae junctions which are gated by Opa1 oligomers. Opa1 has two known functions: maintenance of the cristae junction and mitochondrial fusion. These roles suggest that Opa1 could play a central role in both controlling cyt c release and mitochondrial fusion/fission processes during ischemia/reperfusion. To investigate this concept, we first utilized in vitro real-time imaging to visualize dynamic changes in mitochondria. Oxygen-glucose deprivation (OGD) of neurons grown in culture induced a dual-phase mitochondrial fragmentation profile: (i) fragmentation during OGD with no apoptosis activation, followed by fusion of mitochondrial networks after reoxygenation and a (ii) subsequent extensive fragmentation and apoptosis activation that preceded cell death. We next evaluated changes in mitochondrial dynamic state during reperfusion in a rat model of global brain ischemia. Evaluation of mitochondrial morphology with confocal and electron microscopy revealed a similar induction of fragmentation following global brain ischemia. Mitochondrial fragmentation aligned temporally with specific apoptotic events, including cyt c release, caspase 3/7 activation, and interestingly, release of the fusion protein Opa1. Moreover, we uncovered evidence of loss of Opa1 complexes during the progression of reperfusion, and electron microscopy micrographs revealed a loss of cristae architecture following global brain ischemia. These data provide novel evidence implicating a temporal connection between Opa1 alterations and dysfunctional mitochondrial dynamics following global brain ischemia.

Chronic pain affects many people world-wide, and this number is continuously increasing. There is a clear link between chronic pain and the development of cardiovascular disease through activation of the sympathetic nervous system. The purpose of this review is to provide evidence from the literature that highlights the direct relationship between sympathetic nervous system dysfunction and chronic pain. We hypothesize that maladaptive changes within a common neural network regulating the sympathetic nervous system and pain perception contribute to sympathetic overactivation and cardiovascular disease in the setting of chronic pain. We review clinical evidence and highlight the basic neurocircuitry linking the sympathetic and nociceptive networks and the overlap between the neural networks controlling the two.

Cardiolipin (CL) is the signature phospholipid of mitochondrial membranes. Although it has long been known that CL plays an important role in mitochondrial bioenergetics, recent evidence in the yeast model indicates that CL is also essential for intermediary metabolism. To gain insight into the function of CL in energy metabolism in mammalian cells, here we analyzed the metabolic flux of [U-¹³C]glucose in a mouse C2C12 myoblast cell line, TAZ-KO, which is CL-deficient because of CRISPR/Cas9-mediated knockout of the CL-remodeling enzyme tafazzin (TAZ). TAZ-KO cells exhibited decreased flux of [U-¹³C]glucose to [¹³C]acetyl-CoA and M2 and M4 isotopomers of tricarboxylic acid (TCA) cycle intermediates. The activity of pyruvate carboxylase, the predominant enzyme for anaplerotic replenishing of the TCA cycle, was elevated in TAZ-KO cells, which also exhibited increased sensitivity to the pyruvate carboxylase inhibitor phenylacetate. We attributed a decreased carbon flux from glucose to acetyl-CoA in the TAZ-KO cells to a ∼50% decrease in pyruvate dehydrogenase (PDH) activity, which was observed in both TAZ-KO cells and cardiac tissue from TAZ-KO mice. Protein–lipid overlay experiments revealed that PDH binds to CL, and supplementing digitonin-solubilized TAZ-KO mitochondria with CL restored PDH activity to WT levels. Mitochondria from TAZ-KO cells exhibited an increase in phosphorylated PDH, levels of which were reduced in the presence of supplemented CL. These findings indicate that CL is required for optimal PDH activation, generation of acetyl-CoA, and TCA cycle function, findings that link the key mitochondrial lipid CL to TCA cycle function and energy metabolism.

Research background. The composition of honey is influenced by the botanical source and geographical area of the nectar from which it is derived. Unifloral honeys reach higher market value than multifloral honeys due to their specific aromas, which result from volatile and phenolic compounds. Experimental approach. The aim of our study is to characterize the phenolic composition of a rare unifloral variety of honey – mint (Mentha spp.) honey. For this purpose, we performed standard physicochemical analyses, pollen analysis, determined total phenolic and flavonoid content, analysed antioxidant activity and performed qualitative and quantitative analyses of phenolic compounds for five mint honeys. Results and conclusions. Our results indicate that mint honey samples have high phenolic content, expressed in gallic acid equivalents, from (76.7±0.6) to (90.1±1.1) mg/100 g, and flavonoid content, expressed as quercetin equivalents, from (6.7±0.6) to (12.5±0.8) mg/100 g. These honey samples also exhibit strong antioxidant activity, expressed as Trolox equivalents, from (33.6±2.8) to (51.3±1.2) mg/100 g and from (14.4±0.8) to (55.1±2.4) mg/100 g when analysed with DPPH and ABTS assays, respectively. Quantitative LC-MS/MS analysis revealed that the most abundant phenols in all samples were chrysin, apigenin and p-coumaric acid. Qualitative LC-MS/MS analysis identified the presence of kaempferide, diosmetin, acacetin and several caffeic acid derivatives. Novelty and scientific contribution. Our study indicates that mint honey contains unique phenolic profiles, which likely contribute to its distinctive aroma and strong antioxidant activity. A detailed description of the rare honey varieties gives beekeepers greater visibility and easier access to the demanding natural product market.