Influence of Microcirculatory Dysfunction on Myocardial Injury after Cardiopulmonary Resuscitation / 生物医学与环境科学（英文）

Objective@#This study aimed to examine the effects of microcirculatory dysfunction and 654-1 intervention after cardiopulmonary resuscitation on myocardial injury.@*Methods@#Landrace pigs were divided into a sham operation group (S group, n= 6), ventricular fibrillation control group (VF-C group, n= 8) and 654-1 intervention group (VF-I group, n= 8). Hemodynamics was recorded at baseline, at recovery of spontaneous circulation (ROSC), and 1 h, 2 h, 4 h and 6 h thereafter. Sidestream dark field (SDF) technology was used to evaluate and monitor the microcirculation flow index, total vessel density, perfusion vessel ratio, De-Backer score, and perfusion vessel density in animal viscera at various time points.@*Results@#After administration of 654-1 at 1.5 h post-ROSC, the hemodynamics in the VF-I group, as compared with the VF-C group, was significantly improved. The visceral microcirculation detected by SDF was also significantly improved in the VF-I group. As observed through electron microscopy, significantly less myocardial tissue injury was present in the VF-I group than the VF-C group.@*Conclusion@#Administration of 654-1 inhibited excessive inflammatory by improving the state of visceral microcirculation.

Protection of intestinal immune barrier against ischemia/reperfusion injury in a swine model using anisodamine hydrobromide

Abstract Intestinal ischemia/reperfusion (I/R) causes barrier impairment and bacterial influx. This study explored the protective effects of anisodamine hydrobromide (AH) on intestinal I/R injury caused by cardiopulmonary resuscitation (CPR) after cardiac arrest (CA). After successful CPR, minipigs were randomly divided into two groups (n = 8): saline and AH (4 mg/kg), and then treated with saline or AH via central venous injection, respectively. The same procedures without ventricular fibrillation initiation were conducted in the Sham group (n = 8). Levels of interferon gamma (IFN-γ) and interleukin 4 (IL-4) were measured at different time points (0, 0.5, 1, 2, 4, and 6 h) in serum and 6 h in gut associated lymphoid tissues (GALTs) after the return of spontaneous circulation (ROSC) to evaluate changes in the proportion of T-helper type 1 (Th1) and T-helper type 2 (Th2). Moreover, the positive culture rates of GALTs were examined to evaluate bacterial translocation. AH treatment markedly alleviated aberrant arterial blood gas and hemodynamics as well as intestinal macroscopic and morphological changes after CPR. Moreover, AH treatment significantly increased IFN-γ and decreased IL-4 in both serum and GALTs. Furthermore, AH treatment dramatically decreased positive bacterial growth in GALTs. AH treatment mitigated immunosuppression caused by intestinal I/R and protected the intestinal immune barrier against bacterial translocation, thereby reducing the risk of secondary intestinal infection

Study on anisodamine hydrobromide improves Th17/Treg imbalance in resuscitated pigs / 中华危重病急救医学

Objective:To investigate whether anisodamine can regulate the ratio of helper T helper cells/regulatory T cells (Th17/Treg) and its protective effect on animals after resuscitation.Methods:Twenty-four Beijing white minipigs were randomly divided into sham operation group (Sham group), resuscitation and normal saline group (SA group), and resuscitation and anisodamine hydrobromide group (AH group), with 8 pigs in each group. In SA group and AH group, ventricular fibrillation was induced by continuous stimulation with intraventricular electrodes for 8 minutes and then resuscitated to establish ischemia/reperfusion (I/R) model. In SA group, after cardiopulmonary resuscitation (CPR), only normal saline was intravenously infused, while in AH group, normal saline and anisodamine hydrobromide were given intravenously at the same time point. Hemodynamic indexes, arterial blood gas analysis indexes, interleukins (IL-17, IL-10) levels in venous blood and IL-17/IL-10 ratio were recorded at 6 different time points: baseline, immediately after return of spontaneous circulation (ROSC), 1 hour, 2 hours, 4 hours and 6 hours after ROSC. The animals were sacrificed at 6 hours after ROSC, and intestinal lymphatic tissues were taken to observe pathological changes under light microscope. At the same time, the levels of IL-17 and IL-10 in intestinal lymphatic tissue were measured (the ratio of IL-17/IL-10 represents the ratio of Th17/Treg cytokines) to evaluate the immune status of the resuscitated animals. The bacterial translocations of different groups were evaluated by culturing intestinal lymphoid tissue.Results:With the extension of ROSC time, the levels of IL-17 in venous blood and the IL-17/IL-10 ratio in pig blood samples continued to decrease, while the levels of IL-10 continued to increase. From 2 hours after ROSC, the IL-17/IL-10 ratio in AH group was significantly higher than that in SA group continued until at 6 hours after ROSC (0.79±0.05 vs. 0.49±0.08, P < 0.05). Light microscopy showed that the number and size of lymph nodules in the cortex of intestinal lymphatic tissue were less in AH group, compared with SA group. Compared with Sham group, the levels of IL-17 and IL-17/IL-10 ratio also decreased in intestinal lymphatic tissue at 6 hours after ROSC [IL-17 (ng/L): 155.23±0.92, 178.76±7.25 vs. 209.21±19.82, IL-17/IL-10 ratio: 1.43±0.13, 1.92±0.18 vs. 3.30±0.31, all P < 0.05], and IL-10 increased significantly (ng/L: 109.85±11.60, 93.55±81.83 vs. 63.45±0.62, all P < 0.05); IL-17/IL-10 ratio in AH group was significantly higher than that in SA group (1.92±0.18 vs. 1.43±0.13, P < 0.05). Tissue culture indicated the intestinal bacterial translocation after resuscitation, suggesting that the animals had immunosuppression and the increased risk of intestinal secondary infection after resuscitation. Compared with SA group, the risk of bacterial translocation was lower than that in AH group [62.5% (5/8) vs. 87.5% (7/8), P < 0.05]. Conclusions:Anisodamine plays an immunomodulatory role by affecting the balance of Th17/Treg cytokines in resuscitated animals, so as to reduce the risk of intestinal secondary infection and has an organ protective effect.