Adipose Triglyceride Lipase Deficiency Aggravates Angiotensin II-Induced Atrial Fibrillation by Reducing Peroxisome Proliferator-Activated Receptor α Activation in Mice.

Atrial fibrillation (AF) is a main risk factor for cerebrovascular diseases but lacks precision therapy. Adipose triglyceride lipase (ATGL) is a key enzyme involved in the intracellular degradation of triacylglycerol and plays an important role in lipid and energy metabolism. However, the role of ATGL in the regulation of AF remains unclear. In this study, AF was induced by infusion of angiotensin II (Ang II, 2000 ng/kg/min) for 3 weeks in male ATGL knockout (KO) mice and age-matched C57BL/6 wild-type mice. The atrial volume was measured by echocardiography. Atrial fibrosis, inflammatory cells, and superoxide production were detected by histologic examinations. The results showed that ATGL expression was significantly downregulated in the atrial tissue of the Ang II-infused mice. Moreover, Ang II-induced increase in the inducibility and duration of AF, atrial dilation, fibrosis, inflammation, and oxidative stress in wild-type mice were markedly accelerated in ATGL KO mice; however, these effects were dramatically reversed in the ATGL KO mice administered with peroxisome proliferator-activated receptor (PPAR)-α agonist clofibric acid. Mechanistically, Ang II downregulated ATGL expression and inhibited PPAR-α activity, activated multiple signaling pathways (inhibiting kappa B kinase α/ß-nuclear factor-κB, nicotinamide adenine dinucleotide phosphate oxidase, and transforming growth factor-ß1/SMAD2/3) and reducing Kv1.5, Cx40, and Cx43 expression, thereby contributing to atrial structural and electrical remodeling and subsequent AF. In summary, our results indicate that ATGL KO enhances AF inducibility, possibly through inhibiting PPAR-α activation and suggest that activating ATGL might be a new therapeutic option for treating hypertensive AF.

Apoptosis is involved in the mechanism of postresuscitation myocardial dysfunction in a porcine model of cardiac arrest.

BACKGROUND: Postresuscitation myocardial dysfunction contributes to the low survival rate after successful resuscitation, but its mechanism remains poorly understood. This study investigated whether caspase 3-mediated apoptosis is activated in the heart after postresuscitation myocardial dysfunction. METHODS: After pigs were subjected to 8 minutes of electrically induced cardiac arrest (CA), standard cardiopulmonary resuscitation was performed. Animals in the post-return of spontaneous circulation (ROSC) group were randomly assigned to be killed (n = 6 per group) at 12 and 24 hours after ROSC, and myocardial specimens were analyzed with electron microscopy, Western blotting, quantitative real-time polymerase chain reaction, and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay. RESULTS: Myocardial function was significantly impaired after ROSC. Expression of Bcl-2, Bax, and caspase 3 protein was markedly increased in the post-ROSC group compared with the sham-operated group (P < .05) at 12 and 24 hours after ROSC, whereas Bcl-2/Bax was significantly reduced in the post-ROSC group compared with the sham-operated group (P < .05). The messenger RNA levels of caspase 3 were significantly elevated at 12 and 24 hours after ROSC, and increases in caspase 3 activity indicated activation of the mitochondrial apoptotic pathway. Typical apoptotic nuclei were observed in cardiomyocytes 24 hours after ROSC. More apoptotic cells were observed in animals that had undergone CA compared with sham-operated animals (P < .05). CONCLUSION: Caspase 3-mediated apoptosis may be one of the main pathologic mechanisms of postresuscitation myocardial injury in a porcine model of CA.

Effect of neutrophil CD64 for diagnosing sepsis in emergency department.

BACKGROUND: The aim of this study is to investigate the diagnostic and prognostic value of neutrophil CD64 (nCD64) as a novel biomarker in sepsis patients. METHODS: One hundred fifty-one adult patients diagnosed with sepsis and 20 age-matched healthy controls were enrolled in the study. Patients with sepsis were further subdivided into a sepsis group and a septic shock group. nCD64 expression, serum procalcitonin (PCT) level, C-reactive protein (CRP) level, and white blood cell (WBC) count were obtained for each patient, and Sequential Organ Failure Assessment (SOFA) scores were calculated. RESULTS: nCD64 expression was higher in the sepsis group with confirmed infection than in the control group. The receiver operating characteristic (ROC) curve of nCD64 was higher than those of SOFA score, PCT, CRP and WBC for diagnosing infection. The area under the curve (AUC) of nCD64 combined with SOFA score was the highest for all parameters. The AUC of nCD64 for predicting 28-day mortality in sepsis was significantly higher than those of PCT, CRP, and WBC, but slightly lower than that of SOFA score. The AUC of nCD64 or PCT combined with SOFA score was significantly higher than that of any single parameter for predicting 28-day mortality. CONCLUSION: nCD64 expression and SOFA score are valuable parameters for early diagnosis of infection and prognostic evaluation of sepsis patients.

Comparison of Shenfu Injection () and epinephrine on catecholamine levels in a porcine model of prolonged cardiac arrest.

OBJECTIVE: To compare the effects of Shenfu Injection (SFI) and epinephrine (EPI) on catecholamine levels in a porcine model of prolonged cardiac arrest (CA). METHODS: After 8 min of untreated ventricular fibrillation, 24 Wuzhishan miniature pigs were randomly assigned to one of the three groups (n=8 per group) and received central venous injection, respectively: SFI group (1 mL/kg), EPI group (20 µg/kg EPI), and normal saline (NS) group. Cardiac output (CO), maximum rate of increase/decrease in left ventricular pressure (±dp/dt), serum levels of EPI, norepinephrine (NE), and dopamine (DA) were determined at baseline and at 0.5, 1, 2, and 4 h after restoration of spontaneous circulation. RESULTS: The duration of cardiopulmonary resuscitation was shorter in the EPI and SFI groups than in the NS group (P<0.05). The EPI level increased significantly after restoration of spontaneous circulation (ROSC) in all three groups, and was significantly different between the EPI group and the other two groups immediately after ROSC (both P<0.01), but these differences gradually disappeared over time. There were no significant differences in NE or DA levels among the three groups, and there were no correlations between catecholamine levels and CO or dp/dt (P>0.05). CONCLUSIONS: SFI did not significantly affect endogenous catecholamine levels during cardiopulmonary resuscitation after prolonged ventricular fibrillation. However, SFI improved oxygen metabolism, and produced a better hemodynamic status compared with EPI. SFI might be a potentially vasopressor drug for the treatment of CA.

Comparison of shock-first strategy and cardiopulmonary resuscitation-first strategy in a porcine model of prolonged cardiac arrest.

OBJECTIVE: The choice of a shock-first or a cardiopulmonary resuscitation (CPR)-first strategy in the treatment of prolonged cardiac arrest (CA) is still controversial. The purpose of this study was to compare the effects of these strategies on oxygen metabolism and resuscitation outcomes in a porcine model of 8min CA. METHODS: Ventricular fibrillation (VF) was electrically induced. After 8min of untreated VF, 24 male inbred Wu-Zhi-Shan miniature pigs were randomized to receive either defibrillation first (ID group) or chest compression first (IC group). In the ID group, a shock was delivered immediately. If the defibrillation attempt failed to attain restoration of spontaneous circulation (ROSC), manual chest compressions were rapidly initiated at a rate of 100compressionsmin(-1), and the compression-to-ventilation ratio was 30:2. If VF persisted after five cycles of CPR, a second defibrillation attempt was made. In the IC group, chest compressions were delivered first, followed by a shock. RESULTS: Hemodynamic variables, the VF waveform and blood gas analysis outcomes were recorded. Oxygen metabolism parameters and the amplitude spectrum area (AMSA) of the VF waveform were computed. There were no significant differences in the rate of ROSC and 24h survival between two groups. The ID group had lower lactic acid levels, higher cardiac output, better oxygen consumption and better oxygen extraction ratio at 4 and 6h after ROSC than the IC group. CONCLUSIONS: In a porcine model of prolonged CA, the choice of a shock-first or CPR-first strategy did not affect the rate of ROSC and 24h survival, but the shock-first strategy might result in better hemodynamic status and better oxygen metabolism than the CPR-first strategy at the first 6h after ROSC.

Expression imbalance of transcription factors GATA-3 and T-bet in post-resuscitation myocardial immune dysfunction in a porcine model of cardiac arrest.

BACKGROUND: This study investigated whether an imbalance in Th1/Th2 cells is involved in the post-resuscitation myocardial immune dysfunction. METHODS: 26 Wuzhishan miniature pigs were randomly divided into return of spontaneous circulation (ROSC) group (n=20) and sham-operated group (n=6), 20 pigs were subjected to 8min of electrically induced cardiac arrest, After successful ROSC, the 16 surviving pigs were randomly assigned to be sacrificed (n=8 per group) at 12 and 24h after ROSC, respectively. CD4(+) and CD8(+) lymphocyte subsets were determined by flow cytometry, interleukin (IL)-4 and interferon (IFN)-γ in the myocardium were measured by ELISA, and protein and mRNA levels of GATA-3 and T-bet were detected in the myocardium by Western blotting and quantitative real-time PCR in the post-ROSC group (n=8 per group) at 12 and 24h after ROSC and sham-operated group (n=6) at 24h after ROSC, respectively. RESULTS: CD4(+) lymphocyte subsets were significantly lower in the post-ROSC group compared with the sham-operated group (P<0.05) at 12 and 24h after ROSC. The levels of myocardium IFN-γ were markedly increased, while IL-4 was significantly decreased in the post-ROSC group compared with the sham-operated group (P<0.05) at 12 and 24h after ROSC. Protein expression and mRNA levels of T-bet were markedly increased in the myocardium of pigs in the post-ROSC group compared with the sham-operated group (P<0.05) at 12 and 24h after ROSC, while GATA-3 was significantly reduced (P<0.05). CONCLUSION: The myocardial immune dysfunction induced by the change in expression levels of the transcription factors GATA-3 and T-bet may be involved in the process of post-resuscitation myocardial injury in a porcine model of cardiac arrest.