Abstract 277: Long-Term Daily Prophylactic Supplement With Melatonin as a Health Care Medicine Significantly Improved Survival and Neurological Outcome After Cardiac Arrest

Circulation ◽  
2019 ◽  
Vol 140 (Suppl_2) ◽  
Author(s):  
Yanan Hu ◽  
Xuyan Zhao ◽  
Mingxin Jin ◽  
Ge Jiang ◽  
Xin Sui ◽  
...  

Introduction: Prophylactic pharmacotherapy for health care in reducing death after cardiac arrest (CA) is an elusive and less explored strategy. Melatonin, a natural health product contributing to sleep, was elevated upon arousal from torpor in hibernating mammals, which increased survival after blood return and reduced reperfusion injury. In this study, we sought to find the effects of long-term daily prophylactic supplement with melatonin as a health care medicine on the victim of CA. Methods: SD rats, 240-340 g, were used in this study. Sham, CA, and melatonin + CA (Mel + CA) groups were included. The rats in the Mel + CA group received daily IP injection of melatonin 100 mg/kg for 14 days. CA was induced by 8 mins asphyxia and followed by manual CPR. The endpoint was 24 h after resuscitation. Neurological outcome was assessed. Hippocampal mitochondrial integrity, dynamics and function were observed. Results: Survival in the Mel + CA group was significantly higher than in the CA group (78% vs. 44%, P = 0.036). NDS was better in the Mel + CA group than the CA group ( P < 0.001). Neurons of CA1 were less damaged in the Mel + CA group than in the CA group (Figure). The mitochondria integrity in the CA group was severely damaged compared with the Mel + CA group. Sirt3 was highly expressed in the Mel + CA group than in the CA group ( P < 0.05). Ac-CypD was lower in the Mel + CA group than in the CA group ( P < 0.05). Drp1 was lower in the Mel + CA group than in the CA group ( P < 0.05). LC3 was highly expressed in the Mel + CA group than in the CA group ( P < 0.05). ΔΨm, mitochondria respiratory rate, and respiratory control rate were higher in the Mel + CA group than in the CA group ( P < 0.05). ROS production was lower in the Mel + CA group ( P < 0.05). Cleaved caspase-3 and caspase-9 were lower in the Mel + CA group ( P < 0.05). Conclusions: Long-term daily prophylactic supplement with melatonin as a health care medicine significantly improved survival, neurological outcome and neuronal mitochondrial function after cardiac arrest.

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiaowei Shi ◽  
Jiong Yu ◽  
Qiaoling Pan ◽  
Yuanqiang Lu ◽  
Lanjuan Li ◽  
...  

Introduction: Although epinephrine is universally acknowledged to increase return of spontaneous circulation (ROSC) after cardiac arrest, its balanced effects on later outcomes remain uncertain, causing potential harm during post-resuscitation phase. Recent studies have questioned the efficacy and potential deleterious effects of epinephrine on long-term survival and neurological outcomes, despite that the adverse relationship between epinephrine dose and outcome can be partially biased by longer CPR duration and underlying comorbidities. This study explored the long-term effect of epinephrine when used in a cohort of patients that underwent cardiac arrest during cardiopulmonary resuscitation.Methods: The data were originally collected from a retrospective institutional database from January 2007 to December 2015 and are now available on Dryad (via: https://doi.org/10.5061/dryad.qv6fp83). Use of epinephrine was coded by dose (&lt;2 mg, 2 mg, 3–4 mg, ≥5 mg). A favorable neurological outcome was defined using a Cerebral Performance Category (CPC) 1 or 2. The association between epinephrine dosing and 3-months neurological outcome was analyzed by univariate analysis and multivariate logistic regression.Results: Univariate and multivariate analysis demonstrated a negative association between total epinephrine dose and neurological outcome. Of the 373 eligible patients, 92 received less than 2 mg of epinephrine, 60 received 2 mg, 97 received 3–4 mg and 124 received more than 5 mg. Compared to patients who received less than 2 mg of epinephrine, the adjusted odds ratio (OR) of a favorable neurological outcome was 0.8 (95% confidence interval [CI]: 0.38–1.68) for 2 mg of epinephrine, 0.43 (95% confidence interval [CI]: 0.21–0.89) for 3–4 mg of epinephrine and 0.40 (95% confidence interval [CI]: 0.17–0.96) for more than 5 mg of epinephrine.Conclusion: In this cohort of patients who achieved ROSC, total epinephrine dosing during resuscitation was associated with a worse neurological outcome three months after cardiac arrest, after adjusting other confounding factors. Further researches are needed to investigate the long-term effect of epinephrine on cardiac arrest patients.


2021 ◽  
Author(s):  
jiacheng he

Abstract Background: Prognostication of the unfavourable neurological outcome(UNO) after Cardiac arrest(CA) is multimodal while blood biomarkers are an attractive option.Serum alkaline phosphatase(ALP) is shown to be associated with ischemic stroke and considered as an independent prognostic factor for long-term functional outcome after acute cerebral infarction.We aimed to study the association between ALP and UNO in 3 months in patients after CA.Methods:Review of consecutive patients admitted to the ICU at Erasme Hospital, Brussels (Belgium) following CA between January 2007 and December 2015. The outcome was the UNO in 3 months. We used multivariable logistic regression models to calculate the adjusted odd ratio (OR) with 95% confidence interval(CI). Interaction and stratified analyses were conducted according to Shock,Dobutamine.used,Hypertension,Cardiac.Etiology and Shockable.Rhythm.Results: We included 374 CA patients. The multivariate logistic regression analyses revealed that the risk of UNO in 3 months after CA was significantly associated with ALP.When ALP was Equal is divided in 3 groups, the risk of ALP>91 level and adverse outcomes was 1.7407 times of ALP<64 level (P for trend=0.19709).In the non-hypertension group, the risk of adverse outcomes increased with increased ALP by 1.018 (1.0041.01,1.032).Conclusions: ALP is an independent risk factor for the UNO in 3 months after CA, especially in non-hypertension. Elevated ALP was significantly associated with increased UNO in 3 months after CA. However, the prediction significance of ALP for long-term neurological outcome in patients after CA is needed further studied.


Hypertension ◽  
2014 ◽  
Vol 64 (suppl_1) ◽  
Author(s):  
Xi Lu ◽  
Ken Chen ◽  
Jing Zeng ◽  
Hongmei Ren ◽  
Chunyu Zeng

Introduction: Epidemiological evidence supports an important association between PM2.5 exposure and hypertension. There are reports that PM2.5 induced hypertension with impaired sodium excretion, however, the mechanisms are not clear. Hypothesis: We hypothesize that PM2.5, via increased ROS levels, increased GRK4 expression, consequently impaired renal D1 receptor function, and lead to hypertension. Methods: We used Sprague-Dawley (SD) rats with in-vivo PM2.5 exposure, and immortalized renal proximal tubule (RPT) cells from Wistar-Kyoto (WKY) rats in-vitro, which behave similarly to freshly obtained RPT cells. Results: Our present study found that long-term exposure of PM2.5 caused hypertension and impaired renal sodium excretion, which might be ascribed to lower D1 receptor expression and higher D1 receptor phosphorylation, accompanied with higher GRK4 expression. The in-vivo results were confirmed in in-vitro study, i.e. PM2.5 increased basal Na+-K+ ATPase activity, decreased D1 receptor mediated inhibitory effect on Na+-K+ ATPase activity, decreased D1 receptor expression and increased D1 receptor phosphorylation in RPT cells. The downregulation of D1 receptor expression and function might be due to higher GRK4 expression, because down-regulation of GRK4 by siRNA reversed the D1 receptor expression and function. Due to the role of ROS on D1 receptor dysfunction, we checked ROS levels, and found plasma ROS levels were higher in PM2.5 treated SD rats. Inhibition of ROS by tempol reduced blood pressure and increased sodium excretion in PM2.5 treated SD rats, accompanied by increased the lower D1 receptor expression, and decreased the hyperphosphorylated D1 receptor and GRK4 expression. Conclusions: Long-term exposure of PM2.5 increases blood pressure by decreased D1 receptor expression and function; ROS, via regulation of GRK4 expression, is taken part in the pathogenesis of PM2.5-induced hypertension.


Circulation ◽  
2018 ◽  
Vol 138 (Suppl_2) ◽  
Author(s):  
Stephan Seewald ◽  
Jan Wnent ◽  
Barbara Jakisch ◽  
Andreas Bohn ◽  
Matthias Fischer ◽  
...  

Introduction: Cardiac arrest is a common event and one of the leading causes of death. Especially within the elderly judgment on if the treatment will be in favor of the patient is a major challenge for the medical team. We evaluated the influence of the age on short and long-term survival after out-of- hospital cardiac arrest (OHCA). Hypothesis: Elderly people survive an out-of-hospital cardiac arrest with good neurological outcome. Methods: For this purpose, we analyzed data of 24,686 out-of-hospital cardiac arrest patients prospectively registered between 2008 and 2017 within the German Resuscitation Registry (GRR). The data records were divided according to different age groups and within the age group after shockable and non-shockable rhythms. The data sets were examined with regard to short and long-term survival. Short term survival was measured by expected and observed return-of-spontaneous circulation based on the RACA-score. The RACA-score is a previously published score to predict ROSC based on readily available variables after arrival of the emergency medical service (EMS) on scene. Long-term survival was differentiated in 24-hour survival, 30-day survival and hospital discharge with good neurological outcome (Cerebral Performance Category 1 and 2). Results: (Table 1) Conclusions: Our data shows that shockable rhythm and younger age are important factors of good neurological outcome after OHCA. Nevertheless, the few cases with shockable rhythms (411 out of 3227) in the elderly (>85 years) showed a favorable neurological outcome in 12.2% (77,2% of all patients with hospital discharge). In the non-shockable group 1.4% (58,3%) of the >85 year old had a good outcome. Data show that a resuscitation attempt in the elderly is not futile, especially if a shockable rhythm is detected. Further studies are necessary to maintain this decision.


2020 ◽  
Vol 9 (9) ◽  
pp. 2916 ◽  
Author(s):  
Ahmad Agil ◽  
Meriem Chayah ◽  
Lucia Visiedo ◽  
Miguel Navarro-Alarcon ◽  
José Manuel Rodríguez Ferrer ◽  
...  

Obesity and associated diabetes (diabesity) impair kidney mitochondrial dynamics by augmenting fission and diminishing fusion, which results in mitochondrial and renal dysfunction. Based on available evidence, the antioxidant activities of melatonin may improve impaired renal mitochondrial function in obese diabetic animals by restoring the imbalanced dynamics through inhibiting fission and promoting fusion. Male Zücker diabetic fatty (ZDF) rats and lean littermates (ZL) were orally treated either with melatonin (10 mg/kg BW/day) (M-ZDF and M-ZL) or vehicle (C-ZDF and C-ZL) for 17 weeks. Kidney function was evaluated by measurement of total urine volume, proteinuria, creatinine clearance, and assessment of kidney mitochondrial dynamics and function. C-ZDF exhibited impaired dynamics and function of kidney mitochondria in comparison to C-ZL. Melatonin improved nephropathy of ZDF rats and modulated their mitochondrial dynamics by reducing expression of Drp1 fission marker and increasing that of fusion markers, Mfn2 and Opa1. Furthermore, melatonin ameliorated mitochondrial dysfunction by increasing respiratory control index and electron transfer chain complex IV activity. In addition, it lowered mitochondrial oxidative status. Our findings show that melatonin supplementation improves nephropathy likely via modulation of the mitochondrial fission/fusion balance and function in ZDF rats.


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