Pentraxin 3 in Cardiovascular Disease Ristagno, Giuseppe; Fumagalli, Francesca; Bottazzi, Barbara ...
Frontiers in immunology,
04/2019, Letnik:
10
Journal Article
Recenzirano
Odprti dostop
The long pentraxin PTX3 is a member of the pentraxin family produced locally by stromal and myeloid cells in response to proinflammatory signals and microbial moieties. The prototype of the pentraxin ...family is C reactive protein (CRP), a widely-used biomarker in human pathologies with an inflammatory or infectious origin. Data so far describe PTX3 as a multifunctional protein acting as a functional ancestor of antibodies and playing a regulatory role in inflammation. Cardiovascular disease (CVD) is a leading cause of mortality worldwide, and inflammation is crucial in promoting it. Data from animal models indicate that PTX3 can have cardioprotective and atheroprotective roles regulating inflammation. PTX3 has been investigated in several clinical settings as possible biomarker of CVD. Data collected so far indicate that PTX3 plasma levels rise rapidly in acute myocardial infarction, heart failure and cardiac arrest, reflecting the extent of tissue damage and predicting the risk of mortality.
Endothelial adherens junctions maintain vascular integrity. Arteries and veins differ in their permeability but whether organization and strength of their adherens junctions vary has not been ...demonstrated in vivo. Here we report that vascular endothelial cadherin, an endothelial specific adhesion protein located at adherens junctions, is phosphorylated in Y658 and Y685 in vivo in veins but not in arteries under resting conditions. This difference is due to shear stress-induced junctional Src activation in veins. Phosphorylated vascular endothelial-cadherin is internalized and ubiquitinated in response to permeability-increasing agents such as bradykinin and histamine. Inhibition of Src blocks vascular endothelial cadherin phosphorylation and bradykinin-induced permeability. Point mutation of Y658F and Y685F prevents vascular endothelial cadherin internalization, ubiquitination and an increase in permeability by bradykinin in vitro. Thus, phosphorylation of vascular endothelial cadherin contributes to a dynamic state of adherens junctions, but is not sufficient to increase vascular permeability in the absence of inflammatory agents.
Hypertension and chronic kidney disease (CKD) are complex traits representing major global health problems. Multiple genome-wide association studies have identified common variants in the promoter of ...the UMOD gene, which encodes uromodulin, the major protein secreted in normal urine, that cause independent susceptibility to CKD and hypertension. Despite compelling genetic evidence for the association between UMOD risk variants and disease susceptibility in the general population, the underlying biological mechanism is not understood. Here, we demonstrate that UMOD risk variants increased UMOD expression in vitro and in vivo. Uromodulin overexpression in transgenic mice led to salt-sensitive hypertension and to the presence of age-dependent renal lesions similar to those observed in elderly individuals homozygous for UMOD promoter risk variants. The link between uromodulin and hypertension is due to activation of the renal sodium cotransporter NKCC2. We demonstrated the relevance of this mechanism in humans by showing that pharmacological inhibition of NKCC2 was more effective in lowering blood pressure in hypertensive patients who are homozygous for UMOD promoter risk variants than in other hypertensive patients. Our findings link genetic susceptibility to hypertension and CKD to the level of uromodulin expression and uromodulin's effect on salt reabsorption in the kidney. These findings point to uromodulin as a therapeutic target for lowering blood pressure and preserving renal function.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
to report the incidence, characteristics, and outcome of in-hospital cardiac arrest (IHCA) in a large Italian region.
all hospitals participating in the IHCA Registry Initiative of Piedmont.
...observational cohort study in adult (>18year old) inpatients resuscitated from IHCA during three consecutive years (2012–2014). The main outcome measures were IHCA incidence and survival to hospital discharge.
A total of1539 arrests in adult inpatients were recorded in the study period, yielding an overall incidence of 1.51 arrests/1000 admissions. The incidence was highest at day 1 after hospital admission and in the morning hours, with a peak at 9.00 a.m. Median age was 77 (interquartile range 68–83) years. The presenting rhythm was ventricular fibrillation/pulseless ventricular tachycardia in 291/1539 (18.9%) cases. A total of 549/1539 (35.7%) patients achieved recovery of spontaneous circulation (ROSC) and 228/1539(14.8%) survived hospital discharge, with 207 (90.8%) of the latter having good neurological outcome (Cerebral Performance Categories CPC 1 or 2).After adjustment for major confounders, a pre-arrest CPC=1, a cardiac cause of arrest, a shockable presenting rhythm, and a shorter duration of resuscitation were independently associated with a higher likelihood of survival to discharge.
in this Italian registry the incidence of IHCA and its circadian distribution were comparable to those in the NCAA registry in the UK. Patients were older and had a lower ROSC rate than these observed in other large IHCA registries, but post-ROSC survival rate and factors affecting survival to discharge were similar.
Dispatcher-assisted cardiopulmonary resuscitation (DA-CPR) has been reported in individual studies to significantly increase the rate of bystander CPR and survival from cardiac arrest.
We undertook a ...systematic review and meta-analysis to evaluate the impact of DA-CPR programs on key clinical outcomes following out-of-hospital cardiac arrest. We searched the PubMED, EMBASE, CINAHL, ERIC and Cochrane Central Register of Controlled Trials databases from inception until July 2018. Eligible studies compared systems with and without dispatcher-assisted CPR programs. The results of included studies were classified into 3 categories for the purposes of more accurate analysis: comparison of outcomes in systems with DA-CPR programs, case-based comparison of DA-CPR to bystander CPR, and case-based comparisons of DA-CPR to no CPR before EMS arrival. The GRADE system was used to assess certainty of evidence at an outcome level. We used random-effects models to produce summary effect sizes across all outcomes.
Of 5531 citations screened, 33 studies were eligible for inclusion. All included studies were observational. Evidence certainty across all outcomes was assessed as low or very low. In system-level and patient-level comparisons, the provision of DA-CPR compared with no DA-CPR was consistently associated with improved outcome across all analyses. Comparison of DA-CPR to bystander CPR produced conflicting results. Findings were consistent across sensitivity analyses and the pediatric sub-group.
These results support the recommendation that dispatchers provide CPR instructions to callers for adults and children with suspected OHCA.
Review registration: PROSPERO- CRD42018091427.
Primary vasopressor efficacy of epinephrine during cardiopulmonary resuscitation (CPR) is due to its α-adrenergic effects. However, epinephrine plays β1-adrenergic actions, which increasing ...myocardial oxygen consumption may lead to refractory ventricular fibrillation (VF) and poor outcome. Effects of a single dose of esmolol in addition to epinephrine during CPR were investigated in a porcine model of VF with an underlying acute myocardial infarction. VF was ischemically induced in 16 pigs and left untreated for 12 min. During CPR, animals were randomized to receive epinephrine (30 µg/kg) with either esmolol (0.5 mg/kg) or saline (control). Pigs were then observed up to 96 h. Coronary perfusion pressure increased during CPR in the esmolol group compared to control (47 ± 21 vs. 24 ± 10 mmHg at min 5, p < 0.05). In both groups, 7 animals were successfully resuscitated and 4 survived up to 96 h. No significant differences were observed between groups in the total number of defibrillations delivered prior to final resuscitation. Brain histology demonstrated reductions in cortical neuronal degeneration/necrosis (score 0.3 ± 0.5 vs. 1.3 ± 0.5, p < 0.05) and hippocampal microglial activation (6 ± 3 vs. 22 ± 4%, p < 0.01) in the esmolol group compared to control. Lower circulating levels of neuron specific enolase were measured in esmolol animals compared to controls (21-3 vs. 2116-52 ng/mL, p < 0.01). In this preclinical model, β1-blockade during CPR did not facilitate VF termination but provided neuroprotection.
Cardiac Magnetic Resonance (CMR) is the gold standard for left ventricular (LV) function assessment in small rodents and, though echocardiography (ECHO) has been proposed as an alternative method, LV ...volumes may be underestimated when marked eccentric remodeling is present. In the present study we described a novel echocardiographic method and we tested the agreement with CMR for LV volumes and ejection fraction calculation in mice with experimental myocardial infarction. Sham-operated and infarcted mice, subjected to Coronary Artery Ligation, underwent ECHO and CMR. Volumes and ejection fraction were calculated by ECHO using a standard Simpson's modified method (ECHO pLAX) or a method from sequential parasternal short axis (ECHO pSAX) acquired mechanically by translating the probe every 1 mm along the left ventricle. The mean differences ±1.96 standard deviation near to zero suggested close agreement between ECHO pSAX and CMR; contrarily ECHO pLAX agreement with CMR was lower. In addition, ECHO was three times shorter and cheaper (Relative cost difference: pLAX: -66% and pSAX -57%) than CMR. In conclusion, ECHO pSAX is a new, fast, cheap and accurate method for LV function assessment in mice.
Abstract
Background
Perioperative cardiac arrest is a rare complication with an incidence of around 1 in 1400 cases, but it carries a high burden of mortality reaching up to 70% at 30 days. Despite ...its specificities, guidelines for treatment of perioperative cardiac arrest are lacking. Gathering the available literature may improve quality of care and outcome of patients.
Methods
The PERIOPCA Task Force identified major clinical questions about the management of perioperative cardiac arrest and framed them into the therapy population P, intervention I, comparator C, and outcome O (PICO) format. Systematic searches of PubMed, Embase, and the Cochrane Library for articles published until September 2020 were performed. Consensus-based treatment recommendations were created using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system. The strength of consensus among the Task Force members about the recommendations was assessed through a modified Delphi consensus process.
Results
Twenty-two PICO questions were addressed, and the recommendations were validated in two Delphi rounds. A summary of evidence for each outcome is reported and accompanied by an overall assessment of the evidence to guide healthcare providers.
Conclusions
The main limitations of our work lie in the scarcity of good quality evidence on this topic. Still, these recommendations provide a basis for decision making, as well as a guide for future research on perioperative cardiac arrest.
OBJECTIVES:Both epinephrine and vasopressin increase aortic and carotid arterial pressure when administered during cardiopulmonary resuscitation. However, we recently demonstrated that epinephrine ...reduces cerebral cortical microcirculatory blood flow. Accordingly, we compared the effects of nonadrenergic vasopressin with those of epinephrine on cerebral cortical microvascular flow together with cortical tissue Po2 and Pco2 as indicators of cortical tissue ischemia.
DESIGN:Randomized, prospective animal study.
SETTING:University-affiliated research laboratory.
SUBJECTS:Domestic pigs.
MEASUREMENTS AND MAIN RESULTS:The tracheae of ten domestic male pigs, weighing 40 ± 2 kg, were noninvasively intubated, and the animals were mechanically ventilated. A frontoparietal bilateral craniotomy was created. Microcirculatory blood flow was quantitated with orthogonal polarization spectral imaging. Blood flow velocity in pial and cortical penetrating vessels measuring <20 μm was graded from 0 (no flow) to 3 (normal). Cerebral cortical tissue carbon dioxide and oxygen tensions (Pbco2 and Pbo2) were measured concurrently using miniature optical sensors. Ventricular fibrillation, induced with an alternating current delivered to the right ventricular endocardium, was untreated for 3 mins. Animals were then randomized to receive central venous injections of equipressor doses of epinephrine (30 μg/kg) or vasopressin (0.4 units/kg) at 1 min after the start of cardiopulmonary resuscitation. After 4 mins of cardiopulmonary resuscitation, defibrillation was attempted. Spontaneous circulation was restored in each animal. However, postresuscitation microvascular flows and Pbo2 were greater and Pbco2 less after vasopressin when compared with epinephrine. We observed that a significantly greater number of cortical microvessels were perfused after vasopressin.
CONCLUSIONS:Cortical microcirculatory blood flow was markedly reduced after epinephrine, resulting in a greater severity of brain ischemia after the restoration of spontaneous circulation in contrast to the more benign effects of vasopressin.
Cardiac arrest, one of the leading causes of death, accounts for numerous clinical studies published each year. This review summarizes the findings of all the randomized controlled clinical trials ...(RCT) on cardiac arrest published in the year 2022. The RCTs are presented according to the following categories: out-of- and in-hospital cardiac arrest (OHCA, IHCA) and post-cardiac arrest care. Interestingly, more than 80% of the RCTs encompassed advanced life support and post-cardiac arrest care, while no studies focused on the treatment of IHCA, except for one that, however, explored the temperature control after resuscitation in this population. Surprisingly, 9 out of 11 RCTs led to neutral results demonstrating equivalency between the newly tested interventions compared to current practice. One trial was negative, showing that oxygen titration in the immediate pre-hospital post-resuscitation period decreased survival compared to a more liberal approach. One RCT was positive and introduced new defibrillation strategies for refractory cardiac arrest. Overall, data from the 2022 RCTs discussed here provide a solid basis to generate new hypotheses to be tested in future clinical studies.
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