Cardiovascular dysfunction is associated with poor outcomes in critically ill children.
We aim to derive an evidence-informed, consensus-based definition of cardiovascular dysfunction in critically ill children.
Electronic searches of PubMed and Embase were conducted from January 1992 to January 2020 using medical subject heading terms and text words to define concepts of cardiovascular dysfunction, pediatric critical illness, and outcomes of interest.
Studies were included if they evaluated critically ill children with cardiovascular dysfunction and assessment and/or scoring tools to screen for cardiovascular dysfunction and assessed mortality, functional status, organ-specific, or other patient-centered outcomes. Studies of adults, premature infants (≤36 weeks gestational age), animals, reviews and/or commentaries, case series (sample size ≤10), and non–English-language studies were excluded. Studies of children with cyanotic congenital heart disease or cardiovascular dysfunction after cardiopulmonary bypass were excluded.
Data were abstracted from each eligible study into a standard data extraction form, along with risk-of-bias assessment by a task force member.
Cardiovascular dysfunction was defined by 9 elements, including 4 which indicate severe cardiovascular dysfunction. Cardiopulmonary arrest (>5 minutes) or mechanical circulatory support independently define severe cardiovascular dysfunction, whereas tachycardia, hypotension, vasoactive-inotropic score, lactate, troponin I, central venous oxygen saturation, and echocardiographic estimation of left ventricular ejection fraction were included in any combination. There was expert agreement (>80%) on the definition.
All included studies were observational and many were retrospective.
The Pediatric Organ Dysfunction Information Update Mandate panel propose this evidence-informed definition of cardiovascular dysfunction.
Clinical studies have shown that insomnia and anxiety are usually accompanied by cardiovascular dysfunction. In traditional Chinese medicine, Schisandra chinensis (SC) and wine processed Schisandra chinensis (WSC) are mainly used for the treatment of dysphoria, palpitation and insomnia. However, little attention was paid to its mechanism. In this study, we monitored the effect of SC and WSC on the nervous system and cardiovascular system of free-moving rats in the real-time. Our results show that SC and WSC can alleviate cardiovascular dysfunction while promoting sleep, and we further explored their potential mechanisms. HPLC-QTOF-MS was used for the quality control of chemical components in SC and WSC. Data sciences international (DSI) physiological telemetry system was applied to collect the electroencephalogram (EEG), electrocardiogram (ECG) and other parameters of free-moving rats to understand the effects of long-term intake of SC and WSC on rats. The content of Cortisol (CORT), neurotransmitters and amino acids in rat pituitary and hypothalamus were analyzed by UPLC-MS to determine the activity of HPA axis. The expression of melatonin receptor MT1 was analyzed by immunofluorescence technique. Our results suggested that SC and WSC may play the role of promoting sleep by increasing the expression level of melatonin receptor MT1 in hypothalamus, and modulate the activity of HPA axis by regulating the levels of the related neurotransmitters and amino acid, so as to improve the abnormal cardiovascular system of rats. This study may provide theoretical support for explicating the advantages of SC and other phytomedicines in the treatment of insomnia.
Diabetic cardiovascular dysfunction is a representative complication of diabetes. Inflammation associated with the onset and exacerbation of type 2 diabetes mellitus (T2DM) is an essential factor in the pathogenesis of diabetic cardiovascular complications. Diabetes-induced myocardial dysfunction is characterized by myocardial fibrosis, which includes structural heart changes, myocardial cell death, and extracellular matrix protein accumulation. The mice groups in this study were divided as follows: Cont, control (db/m mice); T2DM, type 2 diabetes mellitus mice (db/db mice); Vil.G, db/db + vildagliptin 50 mg/kg/day, positive control, dipeptidyl peptidase-4 (DPP-4) inhibitor; Bla.C, db/db + blackcurrant 200 mg/kg/day. In this study, Bla.C treatment significantly improved the homeostatic model evaluation of glucose, insulin, and insulin resistance (HOMA-IR) indices and diabetic blood markers such as HbA1c in T2DM mice. In addition, Bla.C improved cardiac function markers and cardiac thickening through echocardiography. Bla.C reduced the expression of fibrosis biomarkers, elastin and type IV collagen, in the left ventricle of a diabetic cardiopathy model. Bla.C also inhibited TD2M-induced elevated levels of inflammatory cytokines in cardiac tissue (IL-6, IL-1β, TNF-α, and TGF-β). Thus, Bla.C significantly improved cardiac inflammation and cardiovascular fibrosis and dysfunction by blocking inflammatory cytokine activation signals. This showed that Bla.C treatment could ameliorate diabetes-induced cardiovascular complications in T2DM mice. These results provide evidence that Bla.C extract has a significant effect on the prevention of cardiovascular fibrosis, inflammation, and consequent diabetes-induced cardiovascular complications, directly or indirectly, by improving blood glucose profile.
Sepsis is a life-threatening organ dysfunction caused by a host’s dysfunctional response to infection. As is known to all, septic heart disease occurs because pathogens invading the blood stimulate the activation of endothelial cells, causing a large number of white blood cells to accumulate and trigger an immune response. However, in severe sepsis, the hematopoietic system is inhibited, and there will also be a decline in white blood cells, at which time the autoimmune system will also be suppressed. During the immune response, a large number of inflammatory factors are released into cells to participate in the inflammatory process, which ultimately damages cardiac myocytes and leads to impaired cardiac function. N6-methyladenosine (m6A) is a common RNA modification in mRNA and non-coding RNA that affects RNA splicing, translation, stability, and epigenetic effects of some non-coding RNAs. A large number of emerging evidences demonstrated m6A modification had been involved in multiple biological processes, especially for sepsis and immune disorders. Unfortunately, there are limited results provided to analyze the association between m6A modification and sepsis-induced cardiovascular dysfunction (SICD). In this review, we firstly summarized current evidences on how m6A mediates the pathophysiological process in cardiac development and cardiomyopathy to emphasize the importance of RNA methylation in maintaining heart biogenesis and homeostasis. Then, we clarified the participants of m6A modification in extended inflammatory responses and immune system activation, which are the dominant and initial changes secondary to sepsis attack. After that, we deeply analyzed the top causes of SICD and identified the activation of inflammatory cytokines, endothelial cell dysfunction, and mitochondrial failure. Thus, the highlight of this review is that we systematically collected all the related potential mechanisms between m6A modification and SICD causes. Although there is lack of direct evidences on SICD, indirect evidences had been demonstrated case by case on every particular molecular mechanism and signal transduction, which require further explorations into the potential links among the listed mechanisms. This provides novel insights into the understanding of SICD.
Work in preclinical animal models has established that pregnancy complicated by chronic fetal hypoxia and oxidative stress programmes cardiovascular dysfunction in adult offspring. Translating this to the human condition comes with challenges, including the early diagnosis of affected individuals to improve clinical outcomes. We hypothesize that components of programmed cardiovascular dysfunction in offspring can be identified in vivo via analysis of blood pressure variability and heart rate variability and that maternal treatment with the mitochondria-targeted antioxidant MitoQ is protective. Pregnant rats were exposed to normoxia or hypoxia (13% O
) ±MitoQ (500 μM in water), from 6 to 20 days gestation. Offspring were maintained in normoxia postnatally. At 16 weeks of age, 1 male per litter was instrumented with vascular catheters and a femoral blood flow probe under isoflurane anesthesia. After recovery, arterial blood pressure and femoral flow were recorded in conscious, free-moving rats and analyzed. Offspring of hypoxic pregnancy had (1) increased very-low-frequency blood pressure variability (A) and heart rate variability (B), indices consistent with impaired endothelial function and (2) increased heart rate variability low/high-frequency ratio (C) and low-frequency blood pressure variability (D), indices of cardiac and vascular sympathetic hyperreactivity, respectively. MitoQ ameliorated A and B but not C and D. We show that asymptomatic cardiovascular dysfunction in adult offspring programmed by hypoxic pregnancy can be diagnosed in vivo by blood pressure variability and heart rate variability, suggesting that these noninvasive biomarkers could be translated to the clinical setting. MitoQ protected against programmed endothelial dysfunction but not sympathetic hyperreactivity, highlighting the divergent programming mechanisms involved.
Particulate matter (PM) resulting from the combustion of organic matter is known to contribute to cardiopulmonary disease. Despite hypotheses that cardiovascular dysfunction occurring after PM exposures is secondary to lung or systemic inflammation, these studies investigating exposures to PM-containing environmentally persistent free radicals (EPFRs) demonstrate that cardiovascular dysfunction precedes pulmonary inflammation. The cardiopulmonary health consequences of EPFRs have yet to be thoroughly evaluated, especially in healthy, adult mice. Our data suggest the vasculature as a direct target of PM exposure, and our studies aimed to elucidate the mechanisms contributing to EPFR-induced vascular dysfunction.