Takotsubo Cardiomyopathy Induced by Epinephrine Infiltration for Liposuction: Broken Heart Syndrome.

Broken heart syndrome, more commonly known as Takotsubo cardiomyopathy (TCM), is an acute cardiac condition. It is characterized by regional cardiac wall motion abnormalities triggered by physical or emotional stress or administration of catecholamines such as epinephrine. The initial clinical presentation is similar to an acute coronary syndrome and must be ruled out. Visualization of the characteristic wall motion will trigger the diagnosis of TCM. In this case report, we present a 50-year-old woman with additional liposuction and fat grafting after autologous breast reconstruction. Shortly after infiltration with a solution containing epinephrine to achieve vasoconstriction, hypotension and bradycardia was noticed. This escalated into full asystole for which cardiac resuscitation was required. ST-elevations and a decrease in systolic function were clear indicators for urgent coronarography and ventriculography. These confirmed the diagnosis of TCM. Infiltration with epinephrine-containing products to achieve local vasoconstriction is used routinely. Medical professionals should be aware that this can trigger a TCM with an estimated mortality rate of 5%. No evidence of a specific preventive measure currently exists. We know that women with a neurologic or psychiatric comorbidity and high levels of stress are more at risk. Reducing stress and anxiolytic medication prior to surgery could be useful. We also know that the cardiac wall motion abnormality is mainly related to ß-adrenoreceptors. The use of a selective α-adrenoreceptor agonist could be considered. Further research in the pathophysiology and incidence of TCM could improve identification of patients at risk and lead to more effective prevention and treatment.

Transfer of dysbiotic gut microbiota has beneficial effects on host liver metabolism.

Gut microbiota dysbiosis has been implicated in a variety of systemic disorders, notably metabolic diseases including obesity and impaired liver function, but the underlying mechanisms are uncertain. To investigate this question, we transferred caecal microbiota from either obese or lean mice to antibiotic-free, conventional wild-type mice. We found that transferring obese-mouse gut microbiota to mice on normal chow (NC) acutely reduces markers of hepatic gluconeogenesis with decreased hepatic PEPCK activity, compared to non-inoculated mice, a phenotypic trait blunted in conventional NOD2 KO mice. Furthermore, transferring of obese-mouse microbiota changes both the gut microbiota and the microbiome of recipient mice. We also found that transferring obese gut microbiota to NC-fed mice then fed with a high-fat diet (HFD) acutely impacts hepatic metabolism and prevents HFD-increased hepatic gluconeogenesis compared to non-inoculated mice. Moreover, the recipient mice exhibit reduced hepatic PEPCK and G6Pase activity, fed glycaemia and adiposity. Conversely, transfer of lean-mouse microbiota does not affect markers of hepatic gluconeogenesis. Our findings provide a new perspective on gut microbiota dysbiosis, potentially useful to better understand the aetiology of metabolic diseases.

Periodontitis induced by Porphyromonas gingivalis drives periodontal microbiota dysbiosis and insulin resistance via an impaired adaptive immune response.

OBJECTIVE: To identify a causal mechanism responsible for the enhancement of insulin resistance and hyperglycaemia following periodontitis in mice fed a fat-enriched diet. DESIGN: We set-up a unique animal model of periodontitis in C57Bl/6 female mice by infecting the periodontal tissue with specific and alive pathogens like Porphyromonas gingivalis (Pg), Fusobacterium nucleatum and Prevotella intermedia. The mice were then fed with a diabetogenic/non-obesogenic fat-enriched diet for up to 3 months. Alveolar bone loss, periodontal microbiota dysbiosis and features of glucose metabolism were quantified. Eventually, adoptive transfer of cervical (regional) and systemic immune cells was performed to demonstrate the causal role of the cervical immune system. RESULTS: Periodontitis induced a periodontal microbiota dysbiosis without mainly affecting gut microbiota. The disease concomitantly impacted on the regional and systemic immune response impairing glucose metabolism. The transfer of cervical lymph-node cells from infected mice to naive recipients guarded against periodontitis-aggravated metabolic disease. A treatment with inactivated Pg prior to the periodontal infection induced specific antibodies against Pg and protected the mouse from periodontitis-induced dysmetabolism. Finally, a 1-month subcutaneous chronic infusion of low rates of lipopolysaccharides from Pg mimicked the impact of periodontitis on immune and metabolic parameters. CONCLUSIONS: We identified that insulin resistance in the high-fat fed mouse is enhanced by pathogen-induced periodontitis. This is caused by an adaptive immune response specifically directed against pathogens and associated with a periodontal dysbiosis.

[Microbiotes and metabolic diseases: the bases for therapeutic strategies]. / Microbiotes et maladies métaboliques - De nouveaux concepts pour de nouvelles stratégies thérapeutiques.

After more than one and a half century, i.e. since Louis Pasteur work on microbes, fermentation, and diseases, biological science has made a giant step in bacteria knowledge. Thanks to an ultra-powerful "microscope", i.e. ultra-fast DNA sequencing, scientists have been able to read and group within a catalog over the last decade, the gene code of bacteria, i.e. the metagenome at the surface of our epithelia. More recently, live bacteria within adipose tissue, defining a tissue microbiota, as well as bacterial fragments such as DNA within the liver, the brain and the blood have been identified. Metagenomic analyses from large cohorts of patients have uncovered tight correlations between bacterial genes within our intestine and mouth and diseases such as metabolic diseases, diabetes, obesity, some liver diseases, kidney and heart failure as well as vascular diseases. Some causal mechanisms have been proposed in rodents and can set the soil for novel therapeutic strategies that could interfere with both the microbes and the corresponding host targets.

Triggering the adaptive immune system with commensal gut bacteria protects against insulin resistance and dysglycemia.

OBJECTIVE: To demonstrate that glycemia and insulin resistance are controlled by a mechanism involving the adaptive immune system and gut microbiota crosstalk. METHODS: We triggered the immune system with microbial extracts specifically from the intestinal ileum contents of HFD-diabetic mice by the process of immunization. 35 days later, immunized mice were fed a HFD for up to two months in order to challenge the development of metabolic features. The immune responses were quantified. Eventually, adoptive transfer of immune cells from the microbiota-immunized mice to naïve mice was performed to demonstrate the causality of the microbiota-stimulated adaptive immune system on the development of metabolic disease. The gut microbiota of the immunized HFD-fed mice was characterized in order to demonstrate whether the manipulation of the microbiota to immune system interaction reverses the causal deleterious effect of gut microbiota dysbiosis on metabolic disease. RESULTS: Subcutaneous injection (immunization procedure) of ileum microbial extracts prevented hyperglycemia and insulin resistance in a dose-dependent manner in response to a HFD. The immunization enhanced the proliferation of CD4 and CD8 T cells in lymphoid organs, also increased cytokine production and antibody secretion. As a mechanism explaining the metabolic improvement, the immunization procedure reversed gut microbiota dysbiosis. Finally, adoptive transfer of immune cells from immunized mice improved metabolic features in response to HFD. CONCLUSIONS: Glycemia and insulin sensitivity can be regulated by triggering the adaptive immunity to microbiota interaction. This reduces the gut microbiota dysbiosis induced by a fat-enriched diet.

Far from the eyes, close to the heart: dysbiosis of gut microbiota and cardiovascular consequences.

These days, the gut microbiota is universally recognized as an active organ that can modulate the overall host metabolism by promoting multiple functions, from digestion to the systemic maintenance of overall host physiology. Dysbiosis, the alteration of the complex ecologic system of gut microbes, is associated with and causally responsible for multiple types of pathologies. Among the latters, metabolic diseases such as type 2 diabetes and obesity are each distinguishable by a unique gut microbiota profile. Interestingly, the specific microbiota typically found in the blood of diabetic patients also has been observed at the level of atherosclerotic plaque. Here, we report evidence from the literature, as well as a few controversial reports, regarding the putative role of gut microbiota dysbiosis-induced cardiovascular diseases, such as atherosclerosis, which are common comorbidities of metabolic dysfunction.

Mitochondria: a target for neuroprotective interventions in cerebral ischemia-reperfusion.

Evidence obtained over the past two decades shows that reactive oxygen species (ROS) are involved in brain lesions, including those due to cerebral ischemia-reperfusion. The mitochondria are the primary intracellular source of ROS, as they generate huge numbers of oxidative-reduction reactions and use massive amounts of oxygen. When anoxia is followed promptly by reperfusion, the resulting increase in oxygen supply leads to overproduction of ROS. In ischemic tissues, numerous studies have established a direct role for ROS in oxidative damage to lipids, proteins, and nucleic acids. Thus, mitochondria are both the initiator and the first target of oxidative stress. Mitochondrial damage can lead to cell death, given the role for mitochondria in energy metabolism and calcium homeostasis, as well as the ability of mitochondria to release pro-apoptotic factors such as cytochrome C and apoptosis-inducing factor (AIF). This review discusses possible mitochondrion-targeted strategies for preventing ROS-induced injury during reperfusion. The sequence of events that follow oxidative damage provides the outline for the review: thus, we will discuss protection of oxidative phosphorylation, mitochondrial membrane integrity and fluidity, and antioxidant or mild-uncoupling strategies for diminishing ROS production. Among mechanisms of action, we will describe the modulation of mitochondrial permeability transition pore (MPTP) opening, which may not only operate as a physiological Ca(2+) release mechanism, but also contribute to mitochondrial deenergization, release of pro-apoptotic proteins, and protection by ischemic preconditioning (IPC). Finally, we will review genetic strategies for controlling apoptotic protein expression, stimulating mitochondrial oxidative defences, and increasing mitochondrial proliferation.