Background
The major concern in patients who have suffered from cardiac arrest (CA) and undergone successful extracorporeal cardiopulmonary resuscitation (E‐CPR) is poor neurological outcomes. In ...this study, we aimed to introduce a rat model of selective brain perfusion (SBP) during E‐CPR to improve the neurological outcome after CA.
Methods
The rats underwent 7 min of untreated asphyxial CA and then were resuscitated with E‐CPR for 30 min. The right external jugular vein and right femoral artery were separately cannulated to the E‐CPR outflow and inflow. The right common carotid artery was cannulated from the proximal to the distal side for SBP. Subsequently, rats were removed from E‐CPR, wounds were closed, and 90 min of intensive care were provided. Neurological deficit scores were tested after 4 h of recovery when the rats were mechanical ventilation‐free. S100 calcium‐binding protein B (S100B) and glial fibrillary acidic protein (GFAP) were detected through immunohistochemistry (IHC) of brain tissue.
Results
The rats that received SBP while resuscitated by E‐CPR showed markedly better neurological performances after 4‐h recovery than those resuscitated by E‐CPR only. The IHC staining of GFAP and S100B in the hippocampus was low in the rats receiving SBP during E‐CPR, but only GFAP showed significant differences.
Conclusions
We successfully developed a novel and reproducible rat model of SBP while resuscitated by E‐CPR to ameliorate the neurological performances after CA. This achievement might have opportunities for studying how to improve the neurological outcome in the clinical condition.
Extracorporeal cardiopulmonary resuscitation with selective brain perfusion system in a rat model.
Purpose
Caseloads of extracorporeal cardiopulmonary resuscitation (ECPR) have increased considerably, and hospital mortality rates remain high and unpredictable. The present study evaluated the ...effects of the interplay between age and prolonged low-flow duration (LFD) on hospital survival rates in elderly patients to identify subgroups that can benefit from ECPR.
Methods
Adult patients who received ECPR in our institution (2006–2016) were classified into groups 1, 2, and 3 (18–65, 65–75, and > 75 years, respectively). Data regarding ECPR and adverse events during hospitalization were collected prospectively. The primary end point was favorable neurologic outcome (cerebral performance category 1 or 2) at hospital discharge.
Results
In total, 482 patients were divided into groups 1, 2, and 3 (70.5%, 19.3%, and 10.2%, respectively). LFDs were comparable among the groups (40.3, 41.0, and 44.3 min in groups 1, 2, and 3,
P
= 0.781, 0.231, and 0.382, respectively). Favorable neurologic outcome rates were nonsignificantly lower in group 3 than in the other groups (27.6%, 24.7%, and 18.4% for group 1, 2, and 3, respectively). Subgroup analysis revealed that the favorable neurologic outcome rates in group 1 were 36.7%, 25.4%, and 13.0% for LFDs of < 30, 30–60, and > 60 min, respectively (
P
= 0.005); in group 2, they were 32.1%, 21.2%, and 23.1%, respectively (
P
= 0.548); in group 3 they were 25.0%, 20.8%, and 0.0%, respectively (
P
= 0.274).
Conclusion
On emergency consultation for ECPR, age and low-flow duration should be considered together to predict neurologic outcome.
Abstract
Serum indices based on creatinine and cystatin C, including creatinine/cystatin C ratio (Cr/CysC), ratio and difference of estimated glomerular filtration rate (eGFR) based on cystatin C and ...creatinine (eGFRcys/eGFRcre and eGFR
Diff
), and serum creatinine × eGFRcys, are recently identified serum markers for sarcopenia. We aimed to evaluate the association between these serum indices and mortality in patients with chronic kidney disease (CKD). A single-center retrospective cohort study included 1141 adult patients with stage 1–5 CKD between 2016 and 2018. Basic characteristics, comorbidities, laboratory parameters, and serum creatinine and cystatin C values were obtained. Patients were followed up until death, dialysis, transfer to another hospital, or end of the study. The median age (interquartile range) of our participants was 71 (62–81) years. During a median follow-up of 39 months, 116 (10.2%) patients died. Compared to the survivor group, Cr/CysC, eGFRcys/eGFRcre, eGFR
Diff
, and Cr × eGFRcys were all lower in the non-survivors (
p
< 0.001 for all). The receiver operating characteristic curves of serum indices for predicting mortality showed that all four indices had significant discriminative power. Based on the Cox proportional hazard models, lower values of four serum indices, both as continuous and categorical variables, independently predicted mortality. Our findings suggest that low serum indices of Cr/CysC, eGFRcys/eGFRcre, eGFRDiff, and Cr × eGFRcys are independent indicators of mortality in patients with non-dialysis CKD.
Summary Background Extracorporeal life-support as an adjunct to cardiac resuscitation has shown encouraging outcomes in patients with cardiac arrest. However, there is little evidence about the ...benefit of the procedure compared with conventional cardiopulmonary resuscitation (CPR), especially when continued for more than 10 min. We aimed to assess whether extracorporeal CPR was better than conventional CPR for patients with in-hospital cardiac arrest of cardiac origin. Methods We did a 3-year prospective observational study on the use of extracorporeal life-support for patients aged 18–75 years with witnessed in-hospital cardiac arrest of cardiac origin undergoing CPR of more than 10 min compared with patients receiving conventional CPR. A matching process based on propensity-score was done to equalise potential prognostic factors in both groups, and to formulate a balanced 1:1 matched cohort study. The primary endpoint was survival to hospital discharge, and analysis was by intention to treat. This study is registered with ClinicalTrials.gov , number NCT00173615. Findings Of the 975 patients with in-hospital cardiac arrest events who underwent CPR for longer than 10 min, 113 were enrolled in the conventional CPR group and 59 were enrolled in the extracorporeal CPR group. Unmatched patients who underwent extracorporeal CPR had a higher survival rate to discharge (log-rank p<0·0001) and a better 1-year survival than those who received conventional CPR (log rank p=0·007). Between the propensity-score matched groups, there was still a significant difference in survival to discharge (hazard ratio HR 0·51, 95% CI 0·35–0·74, p<0·0001), 30-day survival (HR 0·47, 95% CI 0·28–0·77, p=0·003), and 1-year survival (HR 0·53, 95% CI 0·33–0·83, p=0·006) favouring extracorporeal CPR over conventional CPR. Interpretation Extracorporeal CPR had a short-term and long-term survival benefit over conventional CPR in patients with in-hospital cardiac arrest of cardiac origin. Funding National Science Council, Taiwan.
This study aimed to investigate the relationship of four chronic kidney disease-mineral and bone disorder (CKD-MBD) biomarkers, including intact parathyroid hormone (PTH), fibroblast growth factor 23 ...(FGF23), soluble klotho, and fetuin-A, with aortic stiffness in peritoneal dialysis (PD) patients, comparing those with and without diabetes mellitus (DM). A total of 213 patients (mean age 58 ± 14 years; 81 (38.0%) patients with DM) were enrolled. Their aortic pulse wave velocity (PWV) was measured using pressure applanation tonometry, while serum intact PTH, FGF23, α-klotho, and fetuin-A levels were measured using enzyme-linked immunosorbent assay. Overall, patients with DM had higher aortic PWV than those without (9.9 ± 1.8 vs. 8.6 ± 1.4 m/s, p < 0.001). Among the four CKD-MBD biomarkers, FGF23 levels were significantly lower in DM group (462 127-1790 vs. 1237 251-3120 pg/mL, p = 0.028) and log-FGF23 independently predicted aortic PWV in DM group (β: 0.61, 95% confidence interval: 0.06-1.16, p = 0.029 in DM group; β: 0.10, 95% confidence interval: - 0.24-0.45, p = 0.546 in nonDM group; interaction p = 0.016). In conclusion, the association between FGF23 and aortic PWV was significantly modified by DM status in PD patients.
Microcirculatory dysfunction develops in both septic and cardiogenic shock patients, and it is associated with poor prognosis in patients with septic shock. Information on the association between ...microcirculatory dysfunction and prognosis in cardiogenic shock patients with venoarterial extracorporeal membrane oxygenation (VA-ECMO) support is limited.
Sublingual microcirculation images were recorded using an incident dark-field video microscope at the following time points: within 12 h (T1), 24 h (T2), 48 h (T3), 72 h (T4), and 96 h (T5) after VA-ECMO placement. If a patient could be weaned off VA-ECMO, sublingual microcirculation images were recorded before and after VA-ECMO removal. Microcirculatory parameters were compared between 28-day nonsurvivors and survivors with VA-ECMO support. In addition, the microcirculation and clinical parameters were assessed as prognostic tests of 28-day mortality, and patients were divided into three subgroups according to microcirculation parameters for survival analysis.
Forty-eight patients were enrolled in this study. At T1, the observed heart rate, mean arterial pressure, inotropic score and lactate level of 28-day nonsurvivors and survivors did not differ significantly, but the perfused small vessel density (PSVD) and proportion of perfused vessels (PPV) were lower in the 28-day nonsurvivors than in the survivors. The PSVD and PPV were slightly superior to lactate levels in predicting 28-day mortality (area under curve of 0.68, 0.70, and 0.62, respectively). The subgroup with the lowest PSVD (< 15 mm/mm
) and PPV (< 64%) values exhibited less favorable survival compared with the other two subgroups.
Early microcirculatory parameters could be used to predict the survival of cardiogenic shock patients with VA-ECMO support.
ClinicalTrials.gov, NCT02393274 . Registered on 19 March 2015.
Background
Pulmonary artery (PA) cannulation is an effective extracorporeal life support (ECLS) management for left ventricular (LV) decompression or right ventricular (RV) support. This case series ...explores the results of PA cannulation during ECLS for acute cardiac failure.
Methods
Patients receiving percutaneous PA cannulation between January 2017 and December 2020 in a single institution were retrospectively reviewed. Patients receiving PA cannulation by a surgical cutdown method were excluded. Based on the hemodynamic needs of the patients, percutaneous PA cannulation was applied with ECLS for LV unloading and/or RV support. The primary endpoint was the successful weaning from circulatory support. The secondary endpoints included 30‐day or in‐hospital mortality, significant periprocedural complications, and successful hospital discharge without major complications.
Results
Fifteen patients (13 men, age range 11.2–70.8 years) presented acute heart failure and were initially managed by conventional ECLS mode. Percutaneous PA cannulation was performed for LV unloading in 13 patients (86.67%) and isolated RV circulatory support in two patients (13.33%). Weaning from circulatory support was achieved in 11 patients (73.33%). No significant periprocedural complication, including bleeding, infection, or vascular event requiring surgical exploration, was reported. The 30‐day or in‐hospital mortality rate was 33.33%. Eight cases (53.33%) were successfully discharged without major complications, including permanent stroke or the need for long‐term hemodialysis.
Conclusions
PA cannulation, especially percutaneously performed, was effective and safe for LV unloading and/or RV support during ECLS. Further investigation is required to confirm the efficacy and safety of our approach and management in a larger patient population.
Background
Endothelial dysfunction and peripheral arterial disease (PAD), which disturb skeletal muscle microperfusion, are highly prevalent in patients with chronic kidney disease (CKD). We ...evaluated the association of endothelial dysfunction and PAD with sarcopenia in patients with non‐dialysis CKD.
Methods
This cross‐sectional study included 420 patients with stages 3–5 non‐dialysis CKD aged 69.0 ± 11.8 years. Skeletal muscle index (skeletal muscle mass/height2), handgrip strength, 6‐m gait speed and strength of hip flexion and knee extension were measured. Sarcopenia was defined according to the Asian Working Group for Sarcopenia 2019. Endothelial dysfunction and PAD were assessed using the vascular reactivity index (VRI) and ankle–brachial index (ABI), respectively. A VRI < 1.0 was classified as poor endothelial function, and an ABI < 0.9 was defined as PAD. Additionally, endothelial and inflammatory biomarkers, including intercellular adhesion molecule‐1 (ICAM‐1), vascular cell adhesion molecule‐1 (VCAM‐1), asymmetric dimethylarginine, endothelin‐1 (ET‐1) and interleukin‐6, were measured in a subgroup of 262 patients.
Results
Among the participants, 103 (24.5%) were classified as having sarcopenia. Compared with patients without sarcopenia, those with sarcopenia had significantly lower ABI (1.04 ± 0.16 vs. 1.08 ± 0.15, P = 0.028 for the right ABI; 1.01 ± 0.16 vs. 1.06 ± 0.16, P = 0.002 for the left ABI) and VRI (0.83 ± 0.57 vs. 1.08 ± 0.56, P < 0.001) and had higher serum levels of ICAM‐1 (P < 0.001), VCAM‐1 (P = 0.003) and ET‐1 (P = 0.037). Multivariate logistic regression revealed that, beyond age and body mass index, the average ABI (odds ratio OR: 0.81/0.1 increase; 95% confidence interval CI: 0.67–0.98; P = 0.032) and VRI (OR: 0.93/0.1 increase; 95% CI: 0.88–0.98; P = 0.010) were independently associated with sarcopenia. Among the endothelial biomarkers measured, ICAM‐1 (OR: 2.47/1‐SD increase; 95% CI: 1.62–3.75) and VCAM‐1 (OR: 1.91/1‐SD increase; 95% CI: 1.27–2.87) were independent predictors of sarcopenia. Group stratification based on the cut‐offs of VRI and ABI showed that those with both poor VRI and ABI had the greatest risk for sarcopenia (OR: 4.22; 95% CI: 1.69–10.49), compared with those with normal VRI and ABI.
Conclusions
Endothelial dysfunction and PAD are independently associated with sarcopenia in patients with stages 3–5 CKD, suggesting the dominant role of vascular dysfunction in sarcopenia.
Statins, inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A, are widely used to treat hypercholesterolemia. In addition, statins have been suggested to reduce the risk of cardiovascular events owing ...to their pleiotropic effects on the vascular system, including vasodilation, anti-inflammation, anti-coagulation, anti-oxidation, and inhibition of vascular smooth muscle cell proliferation. The major beneficial effect of statins in maintaining vascular homeostasis is the induction of nitric oxide (NO) bioavailability by activating endothelial NO synthase (eNOS) in endothelial cells. The mechanisms underlying the increased NO bioavailability and eNOS activation by statins have been well-established in various fields, including transcriptional and post-transcriptional regulation, kinase-dependent phosphorylation and protein-protein interactions. However, the mechanism by which statins affect the metabolism of L-arginine, a precursor of NO biosynthesis, has rarely been discussed. Autophagy, which is crucial for energy homeostasis, regulates endothelial functions, including NO production and angiogenesis, and is a potential therapeutic target for cardiovascular diseases. In this review, in addition to summarizing the molecular mechanisms underlying increased NO bioavailability and eNOS activation by statins, we also discuss the effects of statins on the metabolism of L-arginine.
Display omitted
•The regulatory mechanisms of statins in the regulation of eNOS expression and eNOS activity.•The role of L-arginine metabolism in the statins-elicited NO bioavailability.•The potential therapeutic effects of statins on the treatment of vascular diseases.
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