Mechanisms and treatment of anemia related to cardiac arrest. / å¿ƒè„éª¤åœåŽç›¸å ³æ€§è´«è¡€çš„æœºåˆ¶åŠæ²»ç–—.

Cardiac arrest is a common and fatal emergency situation. Recently, an increasing number of studies have shown that anemia in patients with cardiac arrest is closely related to high mortality rates and poor neurological outcomes. Anemia is prevalent among patients with post-cardiac arrest syndrome (PCAS), but its specific pathogenesis remains unclear. The mechanisms may involve various factors, including reduced production of erythropoietin, oxidative stress/inflammatory responses, gastrointestinal ischemic injury, hepcidin abnormalities, iatrogenic blood loss, and malnutrition. Measures to improve anemia related to cardiac arrest may include blood transfusions, administration of erythropoietin, anti-inflammation and antioxidant therapies, supplementation of hematopoietic materials, protection of gastrointestinal mucosa, and use of hepcidin antibodies and antagonists. Therefore, exploring the latest research progress on the mechanisms and treatment of anemia related to cardiac arrest is of significant guiding importance for improving secondary brain injury caused by anemia and the prognosis of patients with cardiac arrest.

[Managing Post Cardiac Arrest Syndrome].

Four conditions occur after cardiac arrest resuscitation and are referred to as the post-cardiac arrest syndrome. Moreover, post-cardiac arrest brain injury has the greatest impact on outcomes. Brain injury can be primary as a result of global cerebral ischemia during cardiac arrest. It may be secondary(reperfusion injury)after initiation of cardiopulmonary resuscitation. After cardiac arrest resuscitation, the patient must be managed in the intensive care unit, and it is recommended to avoid hypotension(MAP<65 mmHg), hypoxemia, and hyperoxemia. Oxygen saturation should be maintained at 94%-98%, normal ventilation(35 mmHg-45 mmHg), and body temperature below 37.5℃ for 72 h after resuscitation. The administration of anticonvulsants for abnormal electroencephalograms did not significantly affect the outcome. Prognosis should be predicted within 24 h to 72 h combining physical examination, biomarkers, electrophysiology, and imaging being predictive of poor outcomes.

Cytokine hemoadsorption with CytoSorb® in post-cardiac arrest syndrome, a pilot randomized controlled trial.

BACKGROUND: Hemoadsorption (HA) might mitigate the systemic inflammatory response associated with post-cardiac arrest syndrome (PCAS) and improve outcomes. Here, we investigated the feasibility, safety and efficacy of HA with CytoSorb® in cardiac arrest (CA) survivors at risk of PCAS. METHODS: In this pilot randomized controlled trial, we included patients admitted to our intensive care unit following CA and likely to develop PCAS: required norepinephrine (> 0.2 µg/kg/min), and/or had serum lactate > 6 mmol/l and/or a time-to-return of spontaneous circulation (ROSC) > 25 min. Those requiring ECMO or renal replacement therapy were excluded. Eligible patients were randomly allocated to either receive standard of care (SOC) or SOC plus HA. Hemoadsorption was performed as stand-alone therapy for 24 h, using CytoSorb® and regional heparin-protamine anticoagulation. We collected feasibility, safety and clinical data as well as serial plasma cytokines levels within 72 h of randomization. RESULTS: We enrolled 21 patients, of whom 16 (76%) had out-of-hospital CA. Median (IQR) time-to-ROSC was 30 (20, 45) minutes. Ten were assigned to the HA group and 11 to the SOC group. Hemoadsorption was initiated in all patients allocated to the HA group within 18 (11, 23) h of ICU admission and conducted for a median duration of 21 (14, 24) h. The intervention was well tolerated except for a trend for a higher rate of aPTT elevation (5 (50%) vs 2 (18%) p = 0.18) and mild (100-150 G/L) thrombocytopenia at day 1 (5 (50%) vs 2 (18%) p = 0.18). Interleukin (IL)-6 plasma levels at randomization were low (< 100 pg/mL) in 10 (48%) patients and elevated (> 1000 pg/mL) in 6 (29%). The median relative reduction in IL-6 at 48 h was 75% (60, 94) in the HA group versus 5% (- 47, 70) in the SOC group (p = 0.06). CONCLUSIONS: In CA survivors at risk of PCAS, HA was feasible, safe and was associated with a nonsignificant reduction in cytokine plasma levels. Future trials are needed to further define the role of HA after CA. Those studies should include cytokine assessment to enrich the study population. TRIAL REGISTRATION: NCT03523039, registered 14 May 2018.

[Effect of electroacupuncture at Baihui ameliorated neurologic deficit and hemodynamic stability in rat model of post-cardiac arrest syndrome].

OBJECTIVE: To observe the results of electroacupuncture (EA) on the resuscitation of a rat model of asphyxia cardiac arrest (CA). And to explore its effect on the neurologic deficits and hemodynamic instability of post-cardiac arrest syndrome (PCAS). METHODS: A total of 107 male SD rats were randomly divided into sham, CA, and EA groups. Each group received arterial catheterization and tracheal intubation. The sham group was not induced asphyxia. Asphyxial cardiac arrest was established by endotracheal tube clamping. Rats in the CA group received basic respiratory support and fluid resuscitation in return of spontaneous circulation (ROSC) and rats in the EA group received EA at Baihui based on the treatment of CA group after ROSC, with a dense-dispersed wave at frequencies of 4-20 Hz, while the current intensity was adjusted minimum to induce a twitch of the scalp, the course of treatment was 30 minutes. The baseline data, hemodynamics after ROSC, neurological deficit score (NDS), pathological changes of brain tissue, and levels of serum biomarker were recorded and compared among the three groups. The 72-hour survival of rats was analyzed by Kaplan-Meier survival curve. Hematoxylin-eosin (HE) staining was used to observe the pathological changes of necrotic neurons in the hippocampal CA1 region of rat brain. Meanwhile, Nissl staining and TdT-mediated dUTP nick-end labeling (TUNEL) were used to detect cell apoptosis and injury. RESULTS: Compared with the CA group, the mean arterial pressure (MAP) in the EA group increased significantly at 15 minutes after ROSC [mmHg (1 mmHg ≈ 0.133 kPa): 125.00 (94.00, 136.25) vs. 92.00 (72.00, 122.50), P < 0.05]. There was no significant difference in the NDS score between the EA group and the sham group. Still, the NDS score of the rats in the CA group at 6 hours after ROSC were significantly lower than that in the sham group (46.00±10.61 vs. 80.00±0.00, P < 0.05). Kaplan-Meier survival curve analysis showed that EA did not improve the 72-hour survival rate of rats (100% in the sham group, 25% in the CA group, and 30% in the EA group, P > 0.05). The analysis by TUNEL showed that the apoptosis rate of neurons in CA1 region of the hippocampus in EA group at 6 hours after ROSC was significantly lower than that in CA group [(62.84±2.67)% vs. (71.29±3.70)%, P < 0.05]. Compared with the CA group, the level of serum S100 calcium binding protein B (S100B) in the EA group at 6 hours after ROSC was significantly lower (ng/L: 19.30±13.87 vs. 132.28±31.67, P < 0.05), but there were no significant differences in the levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) between these two groups. CONCLUSIONS: In the present study, EA at Baihui can stabilize the hemodynamic, moreover, it has a particular neuroprotective effect on PCAS rats. Still, EA at Baihui does not reduce the systemic inflammatory response and improve the survival rate of rats, and its mechanism remains to be verified in further research.

Relative Resilience of Cerebellar Purkinje Cells in a Cardiac Arrest/Resuscitation Rat Model.

BACKGROUND: In studies on cardiac arrest (CA)/resuscitation (R) injury, Purkinje cell degeneration was described, however, with inconsistent data concerning severity and time point of manifestation. Moreover, CA/R studies paid only limited attention to inhibitory stellate interneurons. To this aim, the hypothesis that cerebellar could be relatively resilient toward CA/R because of diverse cellular defense mechanisms including interaction with stellate cells was tested. METHODS: We examined rats with survival times of 6, 24, and 48 h, and 7 and 21 days in comparison with sham- and nonoperated animals. Thereby, we focused on the immunohistochemical expression of cfos, MnSOD, Bcl2, caspase 3, parvalbumin, calbindin D28 k, MAP2, IBA1, and GFAP, especially in the particular sensitivity to CA/R cerebellar lobule IX. Hippocampal CA1 degeneration was demonstrated by expression patterns of MAP2 and NeuN in combination with IBA1 and GFAP. RESULTS/CONCLUSIONS: Comparative analysis of hippocampal CA1 pyramidal cells and cerebellar Purkinje cells confirmed a relative resil-ience of Purkinje cells to CA/R. We found only a notable degeneration of Purkinje cell neuronal fiber network, which, however, not necessarily led to neuronal cell death. To induce significant Purkinje cell loss, a stronger ischemic trigger seems to be needed. As possible Purkinje cell-protecting mechanisms, we would propose: (1) activation of inhibitory stellate cells, shown by cfos, MnSOD, and Bcl2 expression, balancing out ischemia-induced excitation and inhibition of Purkinje cells; (2) translocation of the calcium-buffering system, shown by parvalbumin and calbindin D28 k expression, protecting Purkinje cells from detrimental calcium overload; (3) activation of the neuron-astrocyte cross talk, protecting Purkinje cells from over-excitation by removing potassium and neurotransmitters from the extracellular space; (4) activation of the effective and long-lasting MnSOD defense system; and (5) of the anti-apoptotic protein Bcl2 in Purkinje cells itself. Moreover, the results emphasize the limited comparability of animal CA/R studies because of the heterogeneity of the used experimental regimes.

Variable Selection for Nonparametric Learning with Power Series Kernels.

In this letter, we propose a variable selection method for general nonparametric kernel-based estimation. The proposed method consists of two-stage estimation: (1) construct a consistent estimator of the target function, and (2) approximate the estimator using a few variables by ℓ1-type penalized estimation. We see that the proposed method can be applied to various kernel nonparametric estimation such as kernel ridge regression, kernel-based density, and density-ratio estimation. We prove that the proposed method has the property of variable selection consistency when the power series kernel is used. Here, the power series kernel is a certain class of kernels containing polynomial and exponential kernels. This result is regarded as an extension of the variable selection consistency for the nonnegative garrote (NNG), a special case of the adaptive Lasso, to the kernel-based estimators. Several experiments, including simulation studies and real data applications, show the effectiveness of the proposed method.

Preconditioning but not postconditioning treatment with resveratrol substantially ameliorates post­resuscitation myocardial dysfunction through the PI3K/Akt signaling pathway.

Post­resuscitation myocardial dysfunction (PRMD) is a severe complication that arises in patients after cardiac arrest (CA). However, there are no safe or effective treatment strategies that are currently available to treat these patients. In the present study, it was investigated whether resveratrol administration could inhibit myocardial nitrative stress to alleviate PRMD. CA was induced in Sprague­Dawley rats by trans­oesophageal alternating electrical stimulation, followed by cardiopulmonary resuscitation. Rats were then randomly divided into a preconditioning or a postconditioning group. Left ventricular function (+dP/dtmax and ­dP/dtmin) was recorded for 4 h after the return of spontaneous circulation (ROSC), after which the animals were euthanized. Myocardial nitrative stress was analysed using enzyme­linked immunosorbent assay, western blotting and immunohistochemistry. Wortmannin (a PI3K inhibitor) was used to investigate the involvement of the PI3k/Akt signalling pathway in the cardio­protective activity of resveratrol. After ROSC, resveratrol improved PRMD compared to the vehicle control; however, resveratrol administration significantly improved PRMD in the preconditioning group compared to the postconditioning group. Likewise, resveratrol preconditioning significantly decreased the expression of iNOS and nitrotyrosine in rat hearts but did not significantly ameliorate myocardial nitrative stress. Wortmannin partially inhibited the protective effect of resveratrol preconditioning and resulted in the deterioration of cardiac function and increase in iNOS and nitrotyrosine levels. Resveratrol preconditioning could alleviate PRMD by inhibiting myocardial nitrative stress. The PI3K/Akt signalling pathway may be partially involved in the process.