Background Myocardial dysfunction is the leading cause of early death following successful cardiopulmonary resuscitation (CPR) in people with cardiac arrest (CA), which is potentially driven by cell pyroptosis mediated by NOD‐like receptor pyrin domain 3 (NLRP3) inflammasome. Recently, histone deacetylase 6 (HDAC6) inhibition was shown to exert effective myocardial protection against regional ischemia/reperfusion injury. In this study, we investigated whether tubastatin A, a specific histone deacetylase 6 inhibitor, could improve postresuscitation myocardial dysfunction through the inhibition of NLRP3‐mediated cell pyroptosis and its modulation mechanism. Methods and Results Healthy male white domestic swine were used to establish the model of CA/CPR in vivo, and the H9c2 cardiomyocyte hypoxia/reoxygenation model was used to simulate the CA/CPR process in vitro. Consequently, tubastatin A inhibited NLRP3 inflammasome activation, decreased proinflammatory cytokines production and cell pyroptosis, and increased cell survival after hypoxia/reoxygenation in H9c2 cardiomyocytes in vitro. In addition, tubastatin A increased the acetylated levels of transcription factor EB and its translocation to the nucleus, and its protective effect above was partly abrogated by transcription factor EB short interfering RNA after hypoxia/reoxygenation in H9c2 cardiomyocytes. Similarly, tubastatin A promoted cardiac transcription factor EB nuclear translocation, inhibited NLRP3‐mediated cell pyroptosis, and mitigated myocardial dysfunction after CA/CPR in swine. Conclusions The inhibition of histone deacetylase 6 activity by tubastatin A limited NLRP3 inflammasome activation and cell pyroptosis probably through the enhancement of transcription factor EB signaling, and therefore improved myocardial dysfunction after CA/CPR.
Pulmonary aspergillosis is generally categorized into three groups: allergic bronchopulmonary aspergillosis, chronic pulmonary aspergillosis and invasive pulmonary aspergillosis. Aspergillus overlap syndromes (AOS) defined as the occurrence of more than one form of aspergillus disease in a single individual is not common. We present a 62-year-old-male patient with tachypnea, hypoxemia and shock after 4 weeks of cough, expectoration and intermittent hemoptysis, and 2 days of hyperpyrexia. Cardiac arrest occurring during tracheal intubation was resuscitated successfully. Laboratory examination showed acute kidney failure and severe myelosuppression with leukopenia and thrombocytopenia. Chest computed tomography (CT) scan showed the cavity with aspergilloma in the right upper lung lobe, a mass of consolidation in the right lower lung lobe and hyperdense shadow bronchiectasis in the left lower lobe. Bronchoscopy showed lots of sputum occluding the opening of the right airway bronchus. Laboratory examination showed significantly increased C-reactive protein (CRP) and procalcitonin concentration, serum (1,3)-β-D-glucan (BDG) and aspergillus immunoglobulin G (IgG) levels were also elevated. The metagenomic next-generation sequencing and sputum cultures revealed Klebsiella pneumoniae and Aspergillus flavus infection. Pulmonary aspergillosis, invasive aspergillosis infection and severe pneumonia were diagnosed. Initial caspofungin and meropenem followed by piperacillin-tazobactam sodium and voriconazole were administrated in combination. Continuous renal replacement therapy and mechanical ventilation were also performed. The patient's condition gradually recovered. Oral antifungal therapy was continued for 1 year after discharge and CT images gradually improved. Coinfections with K. pneumoniae and A. flavus in a patient with AOS will complicate clinical conditions. A search of PubMed showed few reports of similar cases. Clinicians should pay enough attention to the polymicrobial interactions and improve clinical management strategies, especially in critically ill patient with AOS.
The objective of this study is to investigate the effects of full airway drainage by fiber bronchoscopy through artificial airway in the treatment of traumatic atelectasis with occult manifestations. From May 2006 to May 2011, 40 cases of occult traumatic atelectasis were enrolled into our prospective study. Group A (n=18) received drainage by nasal bronchoscope; group B underwent airway drainage by fiber bronchoscopy through artificial airway (n=22). The effects of treatment were evaluated by the incidence of adult respiratory distress syndrome (ARDS), lung abscess, and the average length of hospital stay. Compared with nasal fiber-optic treatment, airway drainage by fiber bronchoscopy through artificial airway reduced the incidence of ARDS (p=0.013) and lung abscess (p=0.062) and shortened the mean length of stay (p=0.018). Making the decision to create an artificial airway timely and carry out lung lavage by fiber bronchoscopy through artificial airway played a significant role in the treatment of occult traumatic atelectasis.
During hind limb unloading (HU), the soleus is often in a shortened position and the natural physiological stimulus of muscle spindles is altered, such that muscle spindle activity also changes. Using isolated spindle conditions, the present study investigates the electrophysiological activity and ultrastructure of muscle spindles following HU. Results show that muscle spindle discharges fall into either of two main patterns, single spikes or spike clusters in shortened positions, with a steady frequency of 18-38 spikes/s (mean 29.08 +/- 2.45) in an extended position. Following 14-day HU, afferent discharge activity was significantly altered in soleus muscle spindles. Duration of individual spikes was significantly prolonged, from 0.54 +/- 0.05 ms for control rats to 1.53 +/- 0.25 ms for rats in the HU group. In a shortened position, regular rhythm afferent discharges were obviously depressed, and the majority of muscle spindles became silent, while in an extended position, the discharges remained continuous but with decreased frequency. Results also show that the ultrastructure of muscle spindles experience degenerative changes during HU. Altered muscle spindle afference could possibly modify the activity of motor neurons and further affect the activity of extrafusal fibers.
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