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Objective To observe the myocardial apoptosis and the molecular mechanism of captopril inhibiting myocardial apoptosis on cardiac arrest (CA) after resuscitation in a porcine acute pulmonary embolism (APE) model. Methods In this study, 29 inbred Beijing Landrace wererandomly (random number)divided into four groups (n=5, each group): control, APE-CA, restoration of spontaneous circulation (ROSC)-captopril, and ROSC-saline. The model of CA and ROSC was induced by APE through injection of thrombus followed by cardiopulmonary resuscitation and thrombolytic therapy (urokinase, 15000 U/kg, iv). Ten of 19 pigs with CA recovered to spontaneous circulation were divided randomly into the ROSC-captopril and ROSC-saline groups. Pigs in the ROSC-captopril group were treated with captopril (22.22 mg/kg) via porcine femoral vein at 30 min after ROSC. Pigs in the ROSC-saline group were treated with equal normal saline at 30 min after ROSC. The myocardial tissues were evaluated at 6 h after ROSC. Western blot was used to evaluate the protein levels of Bax, Bcl-2, Caspase-3, phosphorylated (p)-Src and phosphorylated extracellular regulated protein kinase (p-ERK1/2). Immunohistochemistry was used to evaluate the protein expression of p-Src and p-ERK1/2. Enzyme-linked immunosorbent assay was used to detect myocardial Na+-K+-ATPase levels. Statistical analysis was performed using one-way analysis of variance and pearson correlation test. Results Compared with the control group, the protein expression of Bax (0.25±0.01, 0.53±0.01, 0.37±0.05, F=14.16, P<0.05) and Caspase-3 (0.24±0.01, 0.33±0.01, 0.34±0.06, F=7.32, P<0.05) in the APE-CA and ROSC- saline group were increased significantly, and the Bcl-2 expression was significantly decreased (0.56±0.02, 0.19±0.01, 0.37±0.10, F=6.68, P<0.05). Captopril reduced the protein levels of Caspase-3 and Bax, while stimulated the Bcl-2 expression (all P<0.05). Compared with the control group, the protein expression of p-Src and p-ERK1/2 were higher and the Na+-K+-ATPase level was decreased on CA and ROSC induced by APE (all P<0.05). Compared with the APE-CA group, the p-Src expression in the ROSC-captopril group (0.46±0.01 vs. 0.35±0.06, P<0.05) was decreased significantly. Captopril inhibited the activation of p-ERK1/2 than saline group (0.41±0.10 vs. 0.26±0.07, P<0.05), but has no effect on the Na+-K+-ATPase level. The protein expression of p-Src and p-ERK1/2 were positively correlated with the Bax, and negatively correlated with the Bcl-2 respectively. The myocardial Na+-K+-ATPase level negatively correlated with Caspase-3 protein expression. Conclusions The molecular mechanism of cardiomyocyte apoptosis on CA and ROSC induced by APE might be related to decreased Na+-K+-ATPase level and activation of p-Src and p-ERK1/2. The cardiomyocyte apoptosis were inhibited by captopril through reducing the expression of p-Src and p-ERK1/2 in myocardium.
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OBJECTIVE@#To explore the influencing factors and possible mechanism of axial symptoms(AS) after C₃-C₇ single open-door laminoplasty in patients with chronic compression cervical myelopathy.@*METHODS@#The clinical data of 32 patients with multi-segment chronic compression cervical cord disease treated by C₃-C₇ single open-door laminectomy from May 2012 to July 2016 were retrospectively analyzed. Including cervical spondylotic myelopathy of 14 cases, developmental cervical stenosis complicated with cervical myelopathy of 8 cases, ossification of posterior longitudinal ligament(OPLL) of 10 cases. There were 17 males and 15 females, aged from 47 to 82 years old with an average of 57.46 year, the course of disease was 5 to 35 months with an average of 22.4 months. The opening angle(OA), cervical curvature angle(CA), preoperative spinal cord compression rate(PSCR) and postoperative spinal cord shift (PSCS) were recorded. After 2 weeks of surgery, determining whether occurred an AS condition according to the AS assessment criteria, the patients were divided into a axial symptom group and a non-axial symptom group, the general data and imaging parameters of the two groups were compared and the factors that may be postoperative AS were analyzed by binary Logistic regression analysis.@*RESULTS@#At 2 weeks after operation, 13 patients occurred AS. There was no significant difference in gender, age and course of disease between axial symptom group and a non-axial symptom group (>0.05). In axial symptom group, OA was(36.76±9.35)°, CA was(11.53±4.36)°, PSCR was(27.83±1.72)%, PSCS was (3.17±0.81) mm, while in non-axial symptom group, above items were (33.03±10.52)°, (7.71±4.73)°, (25.16±3.59)%, (2.43±0.95) mm, respectively, there was significant difference in CA, PSCR, PSCS between two groups(0.05). The results of the binary Logistic regression analysis of 3 parameters(OA, PSCR, PSCS) and AS showed OA and PSCR were eliminated in dependent variables, and the partial regression coefficient of PSCR was 0.311, and =0.031.@*CONCLUSIONS@#CA, PSCR, and PSCS are related influencing factors of AS, and PSCS is a high risk factor for AS. C₄,₅ nerve traction caused by posterior spinal movement, postoperative dural self-expansion causes greater traction of the spinal cord, excessive deformation of the cervical spinal cord causes autonomic nerve damage or necrosis that dominates blood vessels may be the pathogenesis of AS, but this is only a theoretical inference, and further improved experiment is necessary to verify it in the future.
Subject(s)
Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Cervical Vertebrae , Laminectomy , Laminoplasty , Retrospective Studies , Spinal Cord Diseases , Treatment OutcomeABSTRACT
OBJECTIVE@#To observe the open angle (OA), cervical curvature angle (CA), preoperative spinal cord compression rate(PSCR), postoperative spinal cord shift (PSCS) in patients with chronic compressive cervical myelopathy undergoing C3-7 single open laminoplasty, and to explore the possible mechanism and influencing factors of postoperative average spinal cord drift, so as to provide objective basis for predicting PSCS.@*METHODS@#From May 2012 to July 2016, 32 patients with multi-segmental chronic compressive cervical myelopathy who underwent single-door laminoplasty in our department were analyzed retrospectively, including 14 cases of cervical spondylotic myelopathy, 8 cases of developmental cervical spinal stenosis with cervical myelopathy, and 10 cases of ossification of posterior longitudinal ligament. The OA of cervical spine was measured on CT, the CA was measured on X-ray, the PSCR and PSCS were measured on MRI. The patients were divided into two groups according to PSCS(group A>=2.5 mm, group B0.1), and the partial regression coefficients of OA and PSCR were 0.113 and 0.059 respectively.@*CONCLUSIONS@#PSCS is the result of OA, CA and PSCR, among which PSCR has the most important influence, OA is the second, CA is the least. PSCS can be predicted by 0.059×OA+0.113×PSCR-2.266 equation, which provides a theoretical basis for preoperative evaluation of spinal cord decompression after surgery.
Subject(s)
Aged , Female , Humans , Male , Middle Aged , Cervical Vertebrae , Laminectomy , Laminoplasty , Retrospective Studies , Spinal Cord Diseases , Treatment OutcomeABSTRACT
Objective To explore the effect and mechanism of IncRNA EVADR on the proliferation and migration in human colorectal cancer cell lines HCT116 and LOVO. Methods HCT116 and LOVO cell lines were transfected with IncRNA EVADR by overexpressing lentivirus system. CCK8 assay was performed to measure the growth of HCT116 and LOVO cells after overexpression of EVADR. Transwell migration was performed to determine if EVADR promote HCT116 and LOVO cells migration. Finally, the expression of Ecadherin and transcription factor Snail, Slug, ZEB1 and ZEB2 were detected by Western blot and realtime quantitative PCR respectively. Results We successfully established colorectal cancer cells strains HCT116, LOVO which can stably overexpress IncRNA EVADR and the capacity of proliferation and migration in overexpression group was significantly improved (P＜0.05). The expression of Ecadherin was decreased while mesenchymal markers Snail, Slug, ZEB1 and ZEB2 were increased in EVADR overexpression HCT116 and LOVO cells. Conclusions Overexpression of IncRNA EVADR in HCT116 and LOVO cells can significantly promote the proliferation and migration of HCT116 and LOVO cells which may play an important role in regulating epithelial-mesenchymal transition in colorectal cancer cells.
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Objective To observe the hemodynamic change during cardiac arrest (CA) and after restoration of spontaneous circulation (ROSC) in a porcine acute pulmonary embolism model. Methods A total of 14 inbred Beijing Landraces were used to estalish the model of CA and ROSC induced by acute pulmonary embolism through injection of thrombus followed by cardiopulmonary resuscitation and thrombolytic therapy (urokinase, 15000 U/kg, iv). Five resuscitated pigs restored spontaneous circulation. Hemodynamic changes were determined at baseline, CA, ROSC, and 0.5, 1, 1.5, 2, 2.5, 4, and 6 h after ROSC. Results Compared with the baseline, mean arterial pressure was decreased significantly, mean pulmonary arterial pressure and right ventricular pressure were increased significantly, and the heart rate had no change during CA induced by acute pulmonary embolism. The mean arterial pressure restored normal level gradually after ROSC, but was decreased at 4 h after ROSC compared with the baseline (P<0.05). The heart rate was faster at ROSC and 0.5-2 h after ROSC than the baseline (P<0.05). The mean pulmonary arterial pressure restored the baseline level after ROSC; The right ventricular pressure were decreased at 2.5 h (26.5±11.4)mmHg and 4 h (24.8±9.3)mmHg after ROSC compared with the level during CA (46.2±13.01)mmHg (P<0.05). The systemic vascular resistance peaked at 4 h after ROSC. The pulmonary vascular resistance level at ROSC was higher than the baseline [(96.5±24.8)DS/cm5 vs. (26.5±13.4)DS/cm5, P<0.05], and was decreased at 1 h and 2 h after ROSC, but was increased at 4 h and 6 h after ROSC [(98.5±0.7)DS/cm5 and (98.0±1.4)DS/cm5]. The changes of heart function: compared with the baseline, the left ventricular function at ROSC and 1-6 h after ROSC were declined significantly (all P<0.05), and right cardiac output declined at ROSC and 4 h and 6 h after ROSC (all P<0.05), and the level of cardiac function index was dropped at 1 h and 2 h after ROSC (P<0.05). Conclusions The mean arterial pressure was declined, mean pulmonary arterial pressure, right ventricular pressure and pulmonary vascular resistance were increased, cardiac function was decreased during CA induced by acute pulmonary embolism; After ROSC, hemodynamic changes were described as compensated in the early stage (1-2 h after ROSC) and decompensated (4 h after ROSC) with time.
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<p><b>BACKGROUND</b>Study of lung function in survivor from cardiac arrest (CA) caused by pulmonary thromboembolism (PTE) was rare. The aim of this study was to investigate the variations of postresuscitation lung function after thrombolysis treatment in a CA porcine model caused by PTE.</p><p><b>METHODS</b>After 2 min of untreated CA, pigs of 10-12 weeks with a weight of 30 ± 2 kg (n = 24) were treated with recombinant human tissue plasminogen activator (50 mg). Cardiopulmonary resuscitation (CPR) and ventilation were initiated after drug administration. Pulmonary function and arterial blood gas parameters were measured at baseline, return of spontaneous circulation (ROSC) immediately, and 1 h, 2 h, 4 h, and 6 h after ROSC.</p><p><b>RESULTS</b>The dynamic lung compliance decreased significantly at ROSC immediately and 1 h after ROSC compared to baseline (21.86 ± 2.00 vs. 26.72 ± 2.20 ml/mmHg and 20.38 ± 1.31 vs. 26.72 ± 2.20 ml/mmHg, respectively; P < 0.05; 1 mmHg = 0.133 kPa). Compared with baseline, airway resistance increased significantly at ROSC immediately and 1 h after ROSC (P < 0.05). Respiratory index also increased after ROSC and showed significant differences among baseline, ROSC immediately, and 2 h after ROSC (P < 0.05). Oxygen delivery decreased at ROSC immediately compared to baseline (P < 0.05). The oxygenation index decreased significantly at any time after ROSC compared to baseline (P < 0.05). Extravascular lung water index and pulmonary vascular permeability index (PVPI) showed significant differences at ROSC immediately compared to baseline and 1 h after ROSC (P < 0.05); PVPI at ROSC immediately was also different from 6 h after ROSC (P < 0.05). Ventilation/perfusion ratios increased after ROSC (P < 0.05). Histopathology showed fibrin effusion, bleeding in alveoli, and hemagglutination in pulmonary artery.</p><p><b>CONCLUSIONS</b>Lung function remains abnormal even after CPR with thrombolysis therapy; it is essential to continue anticoagulation and symptomatic treatment after ROSC.</p>
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<p><b>BACKGROUND</b>The success rate of resuscitation in cardiac arrest (CA) caused by pulmonary thromboembolism (PTE) is low. Furthermore, there are no large animal models that simulate clinical CA. The aim of this study was to establish a porcine CA model caused by PTE and to investigate the pathophysiology of CA and postresuscitation.</p><p><b>METHODS</b>This model was induced in castrated male pigs (30 ± 2 kg; n = 21) by injecting thrombi (10-15 ml) via the left external jugular vein. Computed tomographic pulmonary angiography (CTPA) was performed at baseline, CA, and return of spontaneous circulation (ROSC). After CTPA during CA, cardiopulmonary resuscitation (CPR) with thrombolysis (recombinant tissue plasminogen activator 50 mg) was initiated. Hemodynamic, respiratory, and blood gas data were monitored. Cardiac troponins T, cardiac troponin I, creatine kinase-MB, myoglobin, and brain natriuretic peptide (BNP) were measured by enzyme-linked immunosorbent assay. Data were compared between baseline and CA with paired-sample t-test and compared among different time points for survival animals with repeated measures analysis of variance.</p><p><b>RESULTS</b>Seventeen animals achieved CA after emboli injection, while four achieved CA after 5-8 ml more thrombi. Nine animals survived 6 h after CPR. CTPA showed obstruction of the pulmonary arteries. Mean aortic pressure data showed occurrence of CA caused by PTE (Z = -2.803, P = 0.002). The maximal rate of mean increase of left ventricular pressure (dp/dtmax) was statistically decreased (t = 6.315, P = 0.000, variation coefficient = 0.25), and end-tidal carbon dioxide partial pressure (PetCO2) decreased to the lowest value (t = 27.240, P = 0.000). After ROSC (n = 9), heart rate (HR) and mean right ventricular pressure (MRVP) remained different versus baseline until 2 h after ROSC (HR, P = 0.036; MRVP, P = 0.027). Myoglobin was statistically increased from CA to 1 h after ROSC (P = 0.036, 0.026, 0.009, respectively), and BNP was increased from 2 h to 6 h after ROSC (P = 0.012, 0.014, 0.039, respectively).</p><p><b>CONCLUSIONS</b>We established a porcine model of CA caused by PTE. The dp/dtmaxand PetCO2may be important for the occurrence of CA, while MRVP may be more important in postresuscitation.</p>