ABSTRACT
Objective To investigate the protective function of endovascular cooling method on post-resuscitation syndrome (PRS) in porcine cardiac arrest (CA) model and its mechanism.Methods Ventricular fibrillation (VF) was electrically induced and untreated for 8 minutes in 15 healthy male porcines, cardiopulmonary resuscitation (CPR) was then initiated. All successful recovery animals were randomly divided into two groups by random number table. In normal temperature group, the core temperature was maintained at (38.0±0.5) ℃ for 12 hours. In mild hypothermia group, the mild hypothermia treatment was initiated at 5 minutes after successful resuscitation, the treatment of rapid endovascular cooling was performed to reach the target cooling temperature of (33.0±1.0) ℃, and then maintained until 6 hours after resuscitation. Rewarming was implemented at the rate of 0.7 ℃/h until the body temperature reached (38.0±0.5) ℃. Hemodynamic parameters including heart rate (HR), mean arterial blood pressure (MAP), cardiac output (CO) were continually monitored. Right femoral vein blood was collected before VF and 1, 2, 4, 6, 12 and 24 hours after resuscitation, respectively, and the serum concentrations of E-selectin, soluble thrombomodulin (sTM), and interleukin-1β(IL-1β) were determined with enzyme linked immunosorbent assay (ELISA). The survival of porcines at 24 hours after resuscitation was observed, and the neurological deficit score (NDS) was calculated for the surviving porcines. All animals were sacrificed, and brain, heart and lung tissues were collected, after hematoxylin and eosin (HE) staining, the histopathology changes were evaluated under a light microscopy.Results After 8-minute VF, 14 porcines were resuscitated successfully, 7 porcines in normal temperature group and 7 in mild hypothermia group respectively, with the resuscitation success rate of 93.3％. There was no significant difference in body weigh, core temperature, hemodynamics, or blood lactate as well as duration of CPR and the number of defibrillations between the two groups. The core temperature of normal temperature group was maintained at (38.0±0.5) ℃, while in mild hypothermia group, the hypothermia was reduced to the hypothermia range (33.0±1.0) ℃until 6 hours, then rewarmed to normothermia gradually [(38.0±0.5) ℃]. Compared with those before VF, HR was significantly increased after resuscitation in both groups, and MAP and CO were decreased, then they tended to normal. There was no significant difference in hemodynamic parameter at all time points between the two groups. Compared with those before VF, the levels of E-selectin and sTM in serum of the two groups were increased significantly at 1 hour after resuscitation, and they were decreased gradually after reaching the peak at 6 hours, and IL-1β was increased continuously with time. There was no significant difference in E-selectin (μg/L:1.34±0.52 vs. 1.60±0.61), sTM (μg/L: 19.13±0.34 vs. 19.24±0.73), or IL-1β (ng/L: 25.73±0.87 vs. 25.32±0.25) before VF between normal temperature group and mild hypothermia group (allP> 0.05). The levels of E-selection, sTM and IL-1β in mild hypothermia group were significantly lower than those in normal temperature group from 2 hours after resuscitation [E-selection (μg/L): 11.15±2.73 vs. 16.04±3.23, sTM (μg/L): 49.67±3.32 vs. 62.22±1.85, IL-1β (ng/L): 140.51±6.66 vs. 176.29±18.51, allP< 0.05], and E-selection decreased to the baseline level at 12 hours (μg/L: 1.17±0.65 vs. 1.60±0.61,P > 0.05). The 24-hour survival rates of two groups were both 100％. The NDS score of mild hypothermia group was obviously lower than that of normal temperature group (150.0±6.6 vs. 326.4±12.3,P < 0.05). In normal temperature group, neuronal cell necrosis was observed in the cerebral cortex at 24 hours after resuscitation, and nucleus was deeply stained. The myocardial necrosis and alveolar collapse was found. Meanwhile the infiltration of inflammatory cell could be found in the myocardium and alveolar. The brain, lung and myocardium injury were significantly milder in mild hypothermia group as compared with those in normal temperature group.Conclusions The intravascular cooling therapy was a safe and effective method for inducing mild hypothermia after resuscitation. This cooling effect was fast and reliable, and the rewarming speed was controllable and stable. The protective mechanism of mild hypothermia on PRS may be related to inhibiting systemic inflammatory response and reducing vascular endothelial cell injury.
ABSTRACT
Objective To approach the brain protective effect and mechanism of Sini decoction on rats with cardiopulmonary resuscitation (CPR) syndrome.Methods Fifty Sprague-Dawley (SD) rats were divided into sham operation group (n = 10), CPR model group (n = 20) and Sini decoction treatment group (n = 20) by random number table. The rat models were established by trachea clipping to induce cardiac arrest, and after heart beat stopped for 5 minutes, CPR was carried out. In the Sini decoction group, Sini decoction 5 g/kg was given through a stomach tube, once per 24 hours, while in the sham and CPR model groups, the same amount of normal saline was given by the same method at the same time. Venous blood was collected before CPR and 6, 12, 24, 48 and 72 hours after CPR, and the levels of serum interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α) were determined by enzyme linked immunosorbent test (ELISA); after CPR for 72 hours, the rat brain tissue was obtained from all the groups, the content of caspase-3 in brain tissue was detected by immunohistochemistry method, and its protein expression caspase-3 was detected by Western Blot; the apoptosis situation of brain tissue was detected by terminal deoxynucleotidyl transferase-mediated duTP nick end labeling (TUNEL).Results With the prolongation of time, the levels of IL-6 and TNF-α in CPR model and Sini decoction groups showed a tendency firstly increased and then decreased, IL-6 reached its peak value after resuscitation for 24 hours, while TNF-α reached its peak value after resuscitation for 48 hours, and both IL-6 and TNF-α were decreased after resuscitation for 72 hours ; beginning from 6 hours after resuscitation, the levels of serum IL-6 (ng/L: 61.79±1.31, 62.49±1.42 vs. 21.48±0.79) and TNF-α (ng/L: 48.32±1.98, 25.32±1.96 vs. 18.34±2.45) in CPR model and Sini decoction treatment groups were all significantly higher than those in sham group, since 12 hours after resuscitation, the level of IL-6 was significantly lower in Sini decoction than that in CPR model group (ng/L: 70.41±2.21 vs. 88.32±1.59), and since 6 hours after resuscitation, TNF-α was obviously lower in Sini decoction group than that in CPR model group (ng/L: 25.32±1.96 vs. 48.32±1.98, allP < 0.05), both IL-6, TNF-α persisting to 72 hours after resuscitation, and their levels did not return to normal at the end of experiment in the two groups. After the end of resuscitation, the content and protein expression of caspase-3 and rate of cell apoptosis in the brain tissue in CPR model group were significantly higher than those in the sham group [caspase-3 content (A value,×103): 2.59±0.26 vs. 1.57±0.06, caspase-3 protein (gray value): 0.80±0.08 vs. 0.43±0.04, apoptosis rate: (2.01±0.08)% vs. (0.26±0.02)%, allP < 0.05], above indexes in the Sini decoction treatment group were significantly lower than those in the CPR model group [caspase-3 content (A value,×103): 1.89±0.08 vs. 2.59±0.26, caspase-3 protein (gray value): 0.57±0.02 vs. 0.80±0.08, apoptosis rate: (1.03±0.05)% vs. (2.01±0.08)%, allP < 0.05).Conclusion The Sini decoction has a protective effect on rats with post-resuscitation syndrome, and its mechanism is possibly realized by the inhibition of inflammatory factors and reduction of cell apoptosis.
ABSTRACT
Post-resuscitation multiple organ dysfunction syndrome(PR-MODS) is a major cause of low survival rate in patients with cardiac arrest.To fully understand the concept of PR-MODS is beneficial for estimating the state of illness,adjusting the therapy and eventually increasing the survival rate.This article reviews the development of PR-MODS concept and compares it with MODS of other causes,including their pathogeny,pathology,mechanism,diagnosis and therapy.