Obesity is associated with significantly increased cardiovascular (CV) risk and mortality. Several molecular mechanisms underlying this association have been implied, among which the intestinal ...barrier has gained a growing interest. In experimental models of obesity, significant alterations in the intestinal barrier lead to increased intestinal permeability, favoring translocation of microbiome-derived lipopolysaccharide to the bloodstream. This has been shown to result in a two- to threefold increase in its serum concentrations, a threshold named 'metabolic endotoxemia' (ME). ME may trigger toll-like receptor 4-mediated inflammatory activation, eliciting a chronic low-grade proinflammatory and pro-oxidative stress status, which may result in high CV risk and target-organ damage. In this review, we discuss the potential molecular implications of ME on several CV risk factors, such as obesity, insulin resistance, dyslipidemia, and oxidative stress, as well as its potential impact on the development of CV target-organ disease.
Abstract The management of acute hypoxemic respiratory failure frequently includes the use of supraphysiological fractions of inspired oxygen (FiO2 ), which can be beneficial in the short-term but ...not without risks in the long-term, causing acute lung injury (ALI). Over the last few years, much attention has been devoted to the intracellular signaling transduction pathways that lead to hyperoxia-induced cell damage, particularly MAP kinase cascades. Identification of involved signaling molecules and understanding of the regulation of the main signal transduction pathways might provide the basis for improving the outcome of patients under high FiO2 exposure through more effective therapeutic interventions. This review, which includes studies published from 1987 to 2015, presents an overview on recent progresses in the hyperoxia ALI field with special emphasis on potential therapeutic targets and clinical approaches based on the molecular mechanisms underlying hyperoxia-induced inflammation. Further studies are needed to gain deeper insight into controversial molecular mechanisms underlying hyperoxia-induced cell death, which may play a critical role in future pharmacological interventions, as well as into hyperoxia-induced cell damage, that could monitor and therefore prevent hyperoxia ALI.
To test whether remote ischaemic conditioning (RIC) as adjuvant to standard of care (SOC) would prevent progression towards heart failure (HF) after ST-elevation myocardial infarction (STEMI). ...Single-centre parallel 1:1 randomized trial (computerized block-randomization, concealed allocation) to assess superiority of RIC (3 cycles of intermittent 5 min lower limb ischaemia) over SOC in consecutive STEMI patients (NCT02313961, clinical trials.gov). From 258 patients randomized to RIC or SOC, 9 and 4% were excluded because of unconfirmed diagnosis and previously unrecognized exclusion criteria, respectively. Combined primary outcome of cardiac mortality and hospitalization for HF was reduced in RIC compared with SOC (
n
= 231 and 217, respectively; HR = 0.35, 95% CI 0.15–0.78) as well as each outcome in isolation. No difference was found in serum troponin I levels between groups. Median and maximum follow-up time were 2.1 and 3.7 years, respectively. In-hospital HF (RR = 0.68, 95% CI 0.47–0.98), need for diuretics (RR = 0.68, 95% CI 0.48–0.97) and inotropes and/or intra-aortic balloon pump (RR = 0.17, 95% CI 0.04–0.76) were decreased in RIC. On planned 12 months follow-up echocardiography (
n
= 193 and 173 in RIC and SOC, respectively) ejection fraction (EF) recovery was enhanced in patients presenting with impaired left ventricular (LV) function (10% absolute difference in median EF compared with SOC;
P
< 0.001). In addition to previously reported improved myocardial salvage index and reduced infarct size RIC was shown beneficial in a combined hard clinical endpoint of cardiac mortality and hospitalization for HF. Improved EF recovery was also documented in patients with impaired LV function.
We analyzed bleeding and thrombotic complications in COVID-19-associated ARDS requiring extracorporeal membrane oxygenation (ECMO).
This was a single-center observational study of adult subjects ...undergoing ECMO for COVID-19 (
= 67) or all other cause of ARDS (
= 60), excluding trauma patients.
In the COVID-19 group, duration of invasive mechanical ventilation prior to ECMO was lower (2 0-4 d vs 3 1-6 d) and ECMO retrieval less frequent (71% vs 87%). No significant differences were found in Simplified Acute Physiology Score II, Acute Physiology and Chronic Health Evaluation II (APACHE II), or in the in-hospital survival predicted by the Respiratory ECMO Survival Prediction score. During the first 7 d of ECMO support, the COVID-19 group presented higher platelets and fibrinogen, lower activated partial thromboplastin time, but no differences in D-dimer. Thrombotic complications were similar between groups. Higher rates of severe bleeding, namely airway bleeding (37.3% vs 15.0%) and hemothorax (13.4% vs 3.3%), were found in COVID-19, with lower hemoglobin and higher red blood cell transfusions. COVID-19 ARDS was associated with longer ECMO duration (47 17-80 d vs 19 12-30 d) and absence of a statistically significant difference concerning in-hospital mortality.
COVID-19-associated ARDS requiring ECMO presented high rates of severe bleeding complications and a protracted course. Further studies are needed to clarify the risks and benefits of ECMO in severe COVID-19-associated ARDS.
Cardiac tamponade is a potentially life-threatening complication during extracorporeal membrane oxygenation (ECMO). In this study, the authors assessed the incidence, patient characteristics, and ...risk factors for mortality of cardiac tamponade during ECMO.
The authors queried the Extracorporeal Life Support Organization (ELSO) Registry from 1997 to 2021 for all adults with cardiac tamponade as a reported complication during ECMO.
Cardiac tamponade was reported in 2,176 (64% men; 53.8 ± 0.33 years) of 84,430 adults (2.6%).
Venoarterial ECMO was the main configuration (78%), followed by venovenous ECMO (VV ECMO) (18%), for cardiac (67%), pulmonary (21%) support, and extracorporeal cardiopulmonary resuscitation (ECPR) (12%). Percutaneous cannulation was performed in 51%, with the femoral vein and femoral artery as the most common sites for drainage and return cannulae, with dual-lumen cannulae in 39% of VV ECMO. Hospital survival was lower (35% v 49%; p < 0.01) when compared with that of all adults from the ELSO Registry. In multivariate analysis, age, aortic dissection and/or rupture, COVID-19, ECPR, pre-ECMO renal-replacement therapy, and prone position are associated with hospital mortality, whereas ECMO for pulmonary support is associated with hospital survival. Similarly, renal, cardiovascular, metabolic, neurologic, and pulmonary complications occurred more frequently in nonsurvivors.
Cardiac tamponade is a rare complication during ECMO that, despite being potentially reversible, is associated with high hospital mortality. Venoarterial ECMO is the most common configuration. ECMO for pulmonary support was associated with higher survival, and ECPR was associated with higher mortality. In these patients, other ECMO-related complications were frequently reported and associated with hospital mortality.
We investigated the endogenous production of apelin and the cardiac and pulmonary effects of its chronic administration in monocrotaline (MCT)-induced pulmonary hypertension (PH). Male Wistar rats ...were injected with MCT (60 mg/kg sc) or vehicle (day 0). One week later, these animals were randomly treated during 17 days with pyroglutamylated apelin-13 (Pyr-AP13; 200 microg*kg(-1)*day(-1) ip) or a similar volume of saline, resulting in four groups: sham (n = 11), sham-AP (n = 11), MCT (n = 16), and MCT-AP (n = 13). On day 25, right ventricular (RV) and left ventricular (LV) hemodynamic and morphometric parameters were assessed. Tissue and plasma samples were collected for histological and molecular analysis. When compared with sham, the MCT group presented a significant increase of RV mass (166 +/- 38%), diameter of cardiomyocyte (40 +/- 10%), myocardial fibrosis (95 +/- 20%), peak systolic pressure (99 +/- 22%), peak rate of ventricular pressure rise (dP/dt(max); 74 +/- 24%), peak rate of ventricular pressure decline (dP/dt(min); 73 +/- 19%), and time constant tau (55 +/- 16%). In these animals, RV expression of apelin (-73 +/- 10%) and its receptor APJ (-61 +/- 20%) was downregulated, whereas mRNA expression of type B natriuretic peptide (9,606 +/- 713%), angiotensinogen (191 +/- 147%), endothelin-1 (RV, 497 +/- 156%; and LV, 799 +/- 309%), plasmatic levels of apelin (104 +/- 48%), and angiotensin 1-7 (161 +/- 151%) were increased. Chronic treatment with Pyr-AP13 significantly attenuated or normalized these changes, preventing apelin-APJ mRNA downregulation and PH-induced neurohumoral activation of several vasoconstrictors, which exacerbates apelin-APJ vasodilator effects. Therefore, apelin delayed the progression of RV hypertrophy and diastolic dysfunction. Together, these observations suggest that the apelin-APJ system may play an important role in the pathophysiology of PH, representing a potential therapeutic target since it significantly attenuates RV overload and PH-induced neurohumoral activation.
Acute interstitial pneumonia (AIP) is a rare idiopathic interstitial lung disease with rapid progressive respiratory failure and high mortality. In the present report, three cases of AIP complicated ...by refractory respiratory failure supported with extracorporeal membrane oxygenation (ECMO) are presented. One male and two female patients (ages 27–59) were included. Venovenous ECMO support was provided using miniaturized systems, with two‐site femoro‐jugular circuit configuration. Despite lung protective ventilation, prone position and neuromuscular blockade, refractory respiratory failure of unknown etiology supervened (ratio of arterial oxygen partial pressure to fractional inspired oxygen 46–130) and ECMO was initiated after 3–7 days of mechanical ventilation. AIP diagnosis was established after exclusion of infectious and noninfectious acute respiratory distress syndrome on the basis of clinical and analytical data, bronchoalveolar lavage analysis and lung imaging, with a confirmatory surgical lung biopsy revealing diffuse alveolar damage of unknown etiology. Immunosuppressive treatment consisted in high‐dose corticosteroids and cyclophosphamide in one case. Two patients survived to hospital discharge. ECMO allowed AIP diagnosis and treatment in the presence of refractory respiratory failure, therefore reducing ventilator‐induced lung injury and bridging lung recovery in two patients. ECMO referral should be considered in refractory respiratory failure if AIP is suspected.
The prognosis of papillary muscle rupture (PMR) leading to acute mitral regurgitation, pulmonary oedema, and cardiogenic shock remains dismal, with survival dependent on prompt recognition and ...surgical intervention. The use of extracorporeal membrane oxygenation (ECMO) for circulatory and/or respiratory support in critically ill patients failing conventional treatment has significantly increased in the past few years, mainly owing to technology improvements that have rendered the provision of this technique simpler and safer. In this report, four cases of refractory cardiopulmonary collapse complicating ischaemic and traumatic PMR successfully managed perioperatively with ECMO are presented. In this context, a review of the potential role of perioperative ECMO support for cardiogenic shock secondary to cardiac mechanical complications is also provided.
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