Upgrading extra corporeal life support to ECMELLA using Impella 5.0 in rescued INTERMACS 1 patients, lactate level matters!

Background: Venoarterial extra corporeal life support (ECLS) is the treatment of choice of Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) class 1 patients, but left ventricle (LV) overload is a complication of ECLS. Unloading the LV by adding Impella 5.0 to ECLS in Impella used in combination with venoarterial extracorporeal membrane oxygenation (ECMELLA) configuration is recommended only in patients with acceptable prognosis.

Ipilimumab-induced renal granulomatous arteritis: a case report.

Background: Immune Checkpoint Inhibitors (ICPIs) are promising new drugs in treatment of advanced tumours targeting cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed cell death protein-1 (PD1) or its ligand (PDL-1). Ipilimumab is a monoclonal antibody targeting the CTLA-4 receptor used in treatment of metastatic melanoma. By increasing activity of the immune system, ICPIs lead to immune-related adverse events, such as dermatitis, colitis or hepatitis.

Cobalamin C Deficiency Induces a Typical Histopathological Pattern of Renal Arteriolar and Glomerular Thrombotic Microangiopathy.

Introduction: Cobalamin C (cblC) deficiency is the most common inborn error of vitamin B metabolism. Renal failure attributed to thrombotic microangiopathy (TMA) has occasionally been described in the late-onset presentation of cblC deficiency, but kidney lesions associated with cblC deficiency remain poorly defined. This study aims to describe the characteristics of kidney disease in cblC deficiency, and to provide a comparative histological analysis with cblC-independent renal TMA.

Patients with severe aortic stenosis and reduced ejection fraction: earlier recovery of left ventricular systolic function after transcatheter aortic valve implantation compared with surgical valve replacement.

Background: Only 50% of patients with aortic stenosis (AS) and low ejection fraction (EF) improve their contractility after surgical aortic valve replacement (AVR). Long-term prognosis of these patients is strongly correlated to EF recovery after the surgery. The aim of this study was to compare the postoperative left ventricular function recovery in patients with severe AS and reduced EF after AVR and transcatheter aortic valve implantation (TAVI).

A leaky splicing mutation affecting SMN1 exon 7 inclusion explains an unexpected mild case of spinal muscular atrophy.

Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder resulting, in most cases, from homozygous deletions of the SMN1 gene or, in rare cases, from SMN1 intragenic mutations. Here we describe the identification and characterization of c.835-3C>T, a novel SMA-causing mutation detected in the intron 6 of the single SMN1 allele of a type IV SMA patient.

Myocardial dysfunction in early state of endotoxemia role of heme-oxygenase-1.

Background: The triggers and cellular mechanisms of cardiac dysfunction have not been clearly established during the early period following challenge with lipopolysaccharides (LPS) (<1 h post-LPS). The aim of the study was to evaluate the myocardial depression during early stage of endotoxemia, the relationship between oxidative stress production and cardiac dysfunction in a rat model of endotoxic shock, and its inhibition by heme-oxygenase-1 (HO-1) overexpression.

Materials And Methods: LPS-induced myocardial deformation was assessed by tissue Doppler imaging and invasive hemodynamic measurements in rats 2 h after LPS challenge.

Toll-like receptors 4 contribute to endothelial injury and inflammation in hemorrhagic shock in mice.

Objective: Hemorrhagic shock followed by resuscitation (HS/R) promotes organ injury by priming cells of the innate immune system for inflammatory response. Toll-like receptors (TLRs) play an important role in signal transduction in shock/resuscitation conditions. Because proinflammatory mediators are a critical event in mesenteric endothelial injury induced by HS/R, we assessed the role of TLR4 or TLR2 in this setting.

Antiphospholipid antibodies induce vascular functional changes in mice: a mechanism of vascular lesions in antiphospholipid syndrome?

A premature atherosclerosis has been presumed in patients with antiphospholipid syndrome. The potential role of antiphospholipid antibodies in the development of atheroma is rather controversial. In this study, we tested the hypothesis that antiphospholipid antibodies could induce atherosclerosis via vascular functional changes.

Intestinal preconditioning prevents inflammatory response by modulating heme oxygenase-1 expression in endotoxic shock model.

Gut mucosal injury observed during ischemia-reperfusion is believed to trigger a systemic inflammatory response leading to multiple organ failure. It should be interesting to demonstrate this relationship between gut and multiple organ failure in a sepsis model. Intestinal preconditioning (PC) can be used as a tool to assess the effect of intestinal ischemia in inflammatory response after LPS challenge.

Improvement of peripheral endothelial dysfunction by protein tyrosine phosphatase inhibitors in heart failure.

Background: Chronic heart failure (CHF) induces endothelial dysfunction characterized by a decrease in nitric oxide (NO) production in response to flow (flow-mediated dilatation [FMD]). Because activation of endothelial NO synthase (eNOS) by flow requires tyrosine phosphorylation, we tested whether endothelial dysfunction could be corrected by increasing phosphotyrosine levels using protein tyrosine phosphatase (PTP) inhibitors and especially inhibitors of PTP1B.

Methods And Results: CHF was induced by coronary ligation in mice, and FMD was assessed in isolated and cannulated mesenteric artery segments (2 mm in length and <300 microm in diameter).

Triple ACE-ECE-NEP inhibition in heart failure: a comparison with ACE and dual ECE-NEP inhibition.

Mortality remains high in chronic heart failure (CHF) because under ACE inhibitor treatment other neurohumoral systems remain/become (de)activated, such as the endothelin and atrial natriuretic peptide pathways. Dual endothelin-converting enzyme-neutral endopeptidase (ECE-NEP) inhibition exerts beneficial effects in experimental CHF, but whether "triple" ACE-ECE-NEP inhibition is superior to ACE or ECE-NEP inhibition is unknown. We compared, in rats with CHF, ACE-ECE-NEP to ACE or ECE-NEP inhibition in terms of left ventricular (LV) hemodynamics and remodeling.

Hemorrhagic shock resuscitation affects early and selective mesenteric artery endothelial function through a free radical-dependent mechanism.

Mesenteric ischemia/reperfusion occurring during hemorrhagic shock and resuscitation (H/R) induces a systemic inflammatory response and damages endothelial cells. Our aim was to investigate whether H/R affects selectively mesenteric vascular reactivity and the roles of free radicals and inducible nitric oxide (NO) synthase (iNOS) in these changes. Rats subjected to H (30 min)/R (60 min) in the presence or absence of the free radical scavenger N-2 mercaptopropionyl glycine (MPG), or the specific inhibitor of iNOS [(3) N-(3-aminomethyl)benzyl) acetaminide; 1400W] were studied.

Coronary endothelial cells: a target of ischemia reperfusion and its treatment?

Ischemia/reperfusion injury of the heart is not limited to cardiomyocytes but also extends to coronary vascular cells, and especially coronary endothelium. Indeed, in different animal models, ischemia followed by reperfusion (but not ischemia alone) markedly decreases endothelium-dependent relaxations of coronary arteries, and especially those induced by nitric oxide (NO), while endothelium-independent responses and smooth muscle responsiveness are usually maintained. Such injury to the endothelium appears to depend on the increased production of oxygen-derived free radicals upon reperfusion, leading to an increased degradation of NO and an acute inflammatory response characterized by an increased adhesion of neutrophils to endothelial cells.

Sustained improvement of cardiac function and prevention of cardiac remodeling after long-term dual ECE-NEP inhibition in rats with congestive heart failure.

Acute inhibition of endothelin converting enzyme (ECE) and neutral endopeptidase (NEP) exerts beneficial hemodynamic effects in chronic heart failure (CHF). However, the long-term effects of dual ECE-NEP inhibition are unknown. We evaluated, in rats with CHF, the long-term effects of the dual ECE-NEP inhibitor CGS 26303 (10 mg.

Alpha2-adrenoceptor ligands inhibit alpha1-adrenoceptor-mediated contraction of isolated rat arteries.

The experiments in this study were designed to investigate the potential relaxing effects of different compounds known as alpha2-imidazoline ligands (either agonists or antagonists) in isolated rat arteries, and to test the role of nitric oxide (NO) and prostaglandins, in addition to the influence of the nature of the contracting agent in these responses. Segments of mesenteric arteries were isolated and mounted in a small vessel myograph (JP Trading, Aarhus, Denmark) for isometric tension recording, while segments of gracilis muscle arteries were cannulated and studied in the pressurized state using an arteriograph (Living Systems Instrumentation, Burlington, VT, USA). In phenylephrine precontracted mesenteric arteries, the agonists clonidine, BHT920, UK 14304, and rilmenidine, as well as the antagonists idazoxan, yohimbine and rauwolscine, all induced marked relaxations.

NO produced by endothelial NO synthase is a mediator of delayed preconditioning-induced endothelial protection.

Preconditioning with brief periods of ischemia-reperfusion (I/R) induces a delayed protection of coronary endothelial cells against reperfusion injury. We assessed the possible role of nitric oxide (NO) produced during prolonged I/R as a mediator of this endothelial protection. Anesthetized rats were subjected to 20-min cardiac ischemia/60-min reperfusion, 24 h after sham surgery or cardiac preconditioning (1 x 2-min ischemia/5-min reperfusion and 2 x 5-min ischemia/5-min reperfusion).

Emerging concepts of neurohumoral modulation in the treatment of congestive heart failure.

The angiotensin converting enzyme (ACE), endothelin (ET) converting enzyme (ECE) and neutral endopeptidase (NEP) are all zinc-metallopeptidases expressed in almost all the organs, such as heart, vessels and kidneys. While ACE and ECE are respectively involved in the transformation of angiotensin I and Big-ET into angiotensin II and ET-1 respectively, which possess vasoconstrictor and mitogenic properties, NEP is involved in the degradation of atrial natriuric factor (ANF), which possesses vasorelaxant, diuretic/natriuretic and antihypertrophic properties. These three systems are activated in heart failure and modulate the progression of heart failure.

Heat stress increases endothelium-dependent relaxations and prevents reperfusion-induced endothelial dysfunction.

1. Heat stress has been widely used to stimulate the expression of stress proteins and is associated with various cardiovascular changes, including anti-ischaemic effects. However, the effect of heat stress on endothelial function is less clear.

Peroxynitrite triggers a delayed resistance of coronary endothelial cells against ischemia-reperfusion injury.

Experiments were designed to test whether nitric oxide (NO) and peroxynitrite trigger delayed coronary endothelial protection induced by preconditioning (PC) in rats. Prolonged ischemia reperfusion markedly reduced the response of isolated coronary arteries to acetylcholine, and this was prevented by PC performed 24 h earlier. The NO synthase (NOS) inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) administered during PC abolished its delayed endothelial protective effect, whereas the inducible NOS inhibitor N-(3(aminomethyl)benzyl)acetaminide had no effect.

Long-term survival and hemodynamics after endothelin-a receptor antagonism and angiotensin-converting enzyme inhibition in rats with chronic heart failure: monotherapy versus combination therapy.

Background: In patients with congestive heart failure (CHF) receiving ACE inhibitors, acute administration of selective endothelin (ET) antagonists additionally improves systemic and cardiac hemodynamics. We investigated, in a rat model of CHF, whether such acute synergistic effects are sustained and accompanied, in the long term, by an additional limitation of left ventricular remodeling or an increase in survival.

Methods And Results: Rats were subjected to coronary artery ligation and treated for 3 or 9 months with vehicle or with the ACE inhibitor trandolapril (Tr) (0.

Intestinal preconditioning prevents systemic inflammatory response in hemorrhagic shock. Role of HO-1.

Intestinal ischemia-reperfusion has been implicated in the systemic inflammatory response and organ injury in hemorrhagic shock, but the exact role of the intestine has never been directly demonstrated. Preconditioning (PC) with brief periods of intermittent ischemia is a known potent anti-ischemic intervention and thus can be used as a tool to assess the role of local intestinal ischemia-reperfusion injury in systemic inflammatory response. Thus rats were first subjected to sham surgery or intestinal preconditioning with four cycles of 1-min ischemia and 10 min of reperfusion 24 h before hemorrhagic shock followed by resuscitation.

Lack of impairment of nitric oxide-mediated responses in a rat model of high-renin hypertension.

1. Angiotensin (Ang) II triggers the expression of a pro- oxidant phenotype in the vascular wall, suggesting that activation of the renin-angiotensin system (RAS) causes endothelial dysfunction in various pathological situations, such as hypertension. However, this hypothesis has been mostly tested in a setting of exogenous administration of AngII.

Effects of combination of low doses of angiotensin-converting enzyme inhibitor and diuretics on renal function in spontaneously hypertensive rats: comparison between acute and chronic treatment.

The goal of this study was to assess the effect of acute or chronic treatment with S5590, a combination of the angiotensin-converting enzyme inhibitor perindopril (0.76 mg/kg/day) and the diuretic indapamide (0.24 mg/kg/day) on renal function in spontaneously hypertensive rats with moderate renal injury.