P2X7 receptor blockade reduces pyroptotic inflammation and promotes phagocytosis in Vibrio vulnificus infection.

Vibrio vulnificus, a gram-negative bacterium, causes serious wound infections and septicemia. Once it develops into early phase sepsis, hyperinflammatory immune responses result in poor prognosis in patients. The present study aimed to examine the possible underlying pathogenic mechanism and explore potential agents that could protect against V. vulnificus cytotoxicity. Here, we report that infection of mouse macrophages with V. vulnificus triggers antiphagocytic effects and pyroptotic inflammation via ATP-mediated purinergic P2X7 receptor (P2X7R) signaling. V. vulnificus promoted P2X7-dependent nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) p65 translocation, modulating the expression of the inflammasome sensor NLR family pyrin domain containing 3 (NLRP3), adaptor apoptosis-associated speck-like protein containing a card (ASC), and pyroptotic protein gasdermin D (GSDMD) in mouse macrophages. V. vulnificus induced the NLRP3/caspase-1 inflammasome signaling complex expression that drives GSDMD transmembrane pore formation and secretion of interleukin (IL)-1ß, IL-18, and macrophage inflammatory protein-2 (MIP-2). This effect was blocked by P2X7R antagonists, indicating that the P2X7R mediates GSDMD-related pyroptotic inflammation in macrophages through the NF-κB/NLRP3/caspase-1 signaling pathway. Furthermore, blockade of P2X7R reduced V. vulnificus-colony-forming units in the spleen, immune cell infiltration into the skin and lung tissues, and serum concentrations of IL-1ß, IL-18, and MIP-2 in mice. These results indicate that P2X7R plays a vital role in mediating phagocytosis by macrophages and pyroptotic inflammation during V. vulnificus infection and provides new opportunities for therapeutic intervention in bacterial infections.

Combination therapy of iPSC-derived conditioned medium with ceftriaxone alleviates bacteria-induced lung injury by targeting the NLRP3 inflammasome.

The lung is the first and most frequent organ to fail among sepsis patients. The mortality rate of sepsis-related acute lung injury (ALI) is high. Despite appropriate antimicrobial therapy, no treatment strategies are available for sepsis-induced ALI. Stem cell-mediated paracrine signaling is a potential treatment method for various diseases. This study aimed to examine the effects of induced pluripotent stem cell-derived conditioned medium (iPSC-CM) combined with antibiotics on ALI in a rat model of Escherichia coli-induced sepsis. Rats were administered either iPSC-CM or the vehicle (saline) with antibiotics (ceftriaxone). After 72 h, liquid biopsy, bronchoalveolar lavage fluid (BALF), and tissues were harvested for analysis. Survival rates were observed for up to 3 days. Furthermore, we examined the effects of iPSC-CM on cytokine production, metalloproteinase 9 (MMP-9) expression, and NLRP3-ASC interaction in RAW264.7 cells stimulated with lipopolysaccharide/interferon-γ (LPS/IFN-γ). Combined treatment of iPSC-CM with antibiotics significantly improved survival in E. coli-infected rats (p = 0.0006). iPSC-CM ameliorated E. coli-induced infiltration of macrophages, reducing the number of cells in BALF, and suppressing interleukin (IL)-1ß, MIP-2, IL-6, and MMP-9 messenger RNA in lung sections. iPSC-CM treatment attenuated NLRP3 expression and inhibited NLRP3 inflammasome activation by disrupting NLRP3-mediated ASC complex formation in LPS/IFN-γ-primed RAW264.7 cells. This study reveals the mechanisms underlying iPSC-CM-conferred anti-inflammatory activity in ALI through the attenuation of macrophage recruitment to the lung, thus inactivating NLRP3 inflammasomes in macrophages. iPSC-CM therapy may be a useful adjuvant treatment to reduce sepsis-related mortality by ameliorating ALI.

Emergency department overcrowding: Quality improvement in a Taiwan Medical Center.

BACKGROUND/PURPOSE: Overcrowding of hospital emergency departments (ED) is a worldwide health problem. The Taiwan Joint Commission on Hospital Accreditation has stressed the importance of finding solutions to overcrowding, including, reducing the number of patients with >48 h stay in the ED. Moreover, the Ministry of Health and Welfare aims at transferring non-critical patients to district or regional hospitals. We report the results of our Quality Improvement Project (QIP) on ED overcrowding, especially focusing on reducing length of stay (LOS) in ED. METHODS: For QIP, the following 3 action plans were initiated: 1) Changing the choice architecture of patients' willingness to transfer from opt-in to opt-out; 2) increasing the turnover rate of beds and daily monitoring of the number of free beds for boarding ED patients; 3) reevaluation of patients with a LOS of >32 h after the morning shift. RESULTS: Transfer rates increased minimally after implementation of this project, but the sample size was too small to achieve statistical significance. No significant increase was observed in the number of free medical beds, but discharge rates after 12 pm decreased significantly (p < 0.001). The proportion of over 48 h LOSs decreased from 4.9% to 3.7% before and after QIP implementation, respectively (p < 0.001). CONCLUSION: Patients with LOS of >32 h were reevaluated first. After QIP, the proportion of LOSs of >48 h dropped significantly. Changing the choice architecture may require further systemic effort and a longer observation duration. Higher-level administrators will need to formulate a more comprehensive bed management plan to speed up the turnover rate of free inpatient beds.

Parathyroidectomy improves cardiovascular outcome in nondiabetic dialysis patients with secondary hyperparathyroidism.

OBJECTIVE: Secondary hyperparathyroidism and its associated abnormalities in mineral metabolism and haemodynamic changes increase the cardiovascular risk in patients with end-stage renal disease (ESRD). Our objective was to determine the association of parathyroidectomy (PTX) with major cardiovascular events in nondiabetic dialysis patients with severe secondary hyperparathyroidism (SHPTH). DESIGN AND PATIENTS: We performed a cohort study with fifty-three nondiabetic ESRD patients who were treated with maintenance haemodialysis and who had intact parathyroid hormone (PTH) levels > 800 pg/ml. Participants received either only medical therapy or medical therapy and total PTX with autotransplantation for SHPTH. MEASUREMENTS: We evaluated the associations between PTX and major cardiovascular events including death, cerebrovascular accident and myocardial infarction. The biochemical and haemodynamic changes associated with PTX were measured. RESULTS: During the mean follow-up of 72 months, twenty-three patients received only medical treatment (medical group) while thirty patients underwent PTX in addition to medical treatment (PTX group). The two groups were comparable in respect of baseline characteristics. PTX group was found to be associated with a reduced incidence of major cardiovascular events (P = 0·021). A multiple Cox regression analysis showed that the variable significantly associated with major cardiovascular events was treatment modality (medical therapy vs medical therapy and parathyroidectomy, hazard ratio = 26·12, 95% CI = 1·30-526·27, P = 0·033). Blood pressure, haemoglobin, alkaline phosphatase, calcium, phosphate and calcium × phosphate product significantly improved after PTX. CONCLUSIONS: PTX was associated with better cardiovascular outcome in nondiabetic dialysis patients with severe SHPTH.

The role of autonomic nervous system function in hypothermia-mediated sepsis protection.

OBJECTIVE: The objective of this study is to determine whether hypothermia will lessen decreases in heart rate variability and improve outcome in a rat model of sepsis. METHODS: Thirty-six male Sprague-Dawley rats were randomized into 3 groups: control, low sepsis, and high sepsis groups. These groups were each subdivided into a normothermia (37°C) (n = 6) and a hypothermia group (34°C) (n = 6). Cyclophosphamide (100 mg/kg) was administered 5 days before Staphylococcus aureus injection to produce conditions in which sepsis could be induced reliably. Hypothermic rats received temperature reduction for 1 hour post injection. Electrocardiogram was recorded before, after, and 1 day after staphylococcal injection, and the low frequency, high frequency (HF), and LF/HF ratio measurements of heart rate variability and the frequencies of arrhythmia were recorded. The effects of time, sepsis severity, and hypothermia on these variables were analyzed using a multivariate generalized estimation equation mode. RESULTS: Four deaths occurred in the normothermic group, and none, in the hypothermic group. Sepsis of both low and high severity increased low frequency and HF 1 day after sepsis induction. Hypothermia significantly decreased HF in low, but not high sepsis severity. CONCLUSIONS: Hypothermia decreased mortality in septic rats. The influence of hypothermia on HF depended on the severity of the sepsis.

Impact of a targeted temperature management quality improvement project on survival and neurologic outcomes in cardiac arrest patients.

BACKGROUND: Targeted temperature management (TTM) is recommended for postresuscitation care of patients with sudden cardiac arrest (SCA) and its implementation remains challenging. This study aimed to evaluate the newly designed Quality Improvement Project (QIP) to improve the quality of TTM and outcomes of patients with SCA. METHODS: Patients who experienced out-of-hospital cardiac arrest (OHCA) and in-hospital cardiac arrest (IHCA) with return of spontaneous circulation (ROSC) and were treated in our hospital between January 2017 and December 2019 were enrolled retrospectively. All included patients received QIP intervention initiated as follows: (1) Protocols and standard operating procedures were created for TTM; (2) shared decision-making was documented; (3) job training instruction was created; and 4) lean medical management was implemented. RESULTS: Among 248 included patients, the postintervention group (n = 104) had shorter duration of ROSC to TTM than the preintervention group (n = 144) (356 vs 540 minutes, p = 0.042); better survival rate (39.4% vs 27.1%, p = 0.04), and neurologic performance (25.0% vs 17.4%, p < 0.001). After propensity score matching (PSM), patients who received TTM (n = 48 ) had better neurologic performance than those without TTM (n = 48) (25.1% vs 18.8%, p < 0.001). OHCA (odds ratio [OR] = 2.705, 95% CI: 1.657-4.416), age >60 (OR = 2.154, 95% CI: 1.428-3.244), female (OR = 1.404, 95% CI: 1.005-1.962), and diabetes mellitus (OR = 1.429, 95% CI: 1.019-2.005) were negative predictors of survival; while TTM (OR = 0.431, 95% CI: 0.266-0.699) and bystander cardiopulmonary resuscitation (CPR) (OR=0.589, 95% CI: 0.35-0.99) were positive predictors. Age >60 (OR= 2.292, 95% CI: 1.58-3.323) and OHCA (OR= 2.928, 95% CI: 1.858-4.616) were negative predictors of favorable neurologic outcomes; while bystander CPR (OR=0.572, 95% CI: 0.355-0.922) and TTM (OR=0.457, 95% CI: 0.296-0.705) were positive predictors. CONCLUSION: A new QIP with defined protocols, documented shared decision-making, and medical management guidelines improves TTM execution, duration from ROSC to TTM , survival, and neurologic outcomes of cardiac arrest patients.

Sarcopenia is associated with mortality in non-critical elderly patients visiting the emergency department.

Introduction: Geriatric syndrome (GS) increases risk of disability and mortality in older adults. Sarcopenia is a predominant illness of GS and accelerate its progression. This study aimed to investigate associations between mortality, emergency department (ED) re-visits and GS-related illnesses among older adults who visited the ED. Method: This retrospective observational study enrolled elderly patients who visited the ED in our hospital between January 2018 and October 2020. Patients were evaluated for potential sarcopenia, which was defined by both low handgrip strength and calf circumference. Follow-up was at least 6 months. Data of age, gender, mortality, ED re-visits, and GS-related illnesses were collected and analyzed for associations. Results: A total of 273 older adults aged 74 years or older were included, of whom 194 were diagnosed with possible sarcopenia. Older adults with possible sarcopenia also had significantly lower body mass index (BMI); a higher proportion needed assistance with daily activities; more had malnutrition, frailty, and history of falls (all p < 0.001) and acute decline in activities of daily living (p = 0.027). Multivariate analysis showed that possible sarcopenia [adjusted hazard ratio, aHR): 9.89, 95% confidence interval (CI): 1.17-83.81, p = 0.036], living in residential institutions (aHR: 2.85, 95% CI: 1.08-7.50, p = 0.034), and frailty (aHR: 7.30, 95% CI: 1.20-44.62, p = 0.031) were associated with mortality. Aged over 85 years (adjusted odds ratio: 2.44, 95% CI: 1.25-4.80, p = 0.02) was associated with ED re-visits. Conclusion: Sarcopenia is associated with mortality among older adults who visit ED. Initial screening for sarcopenia and relevant risk factors among older adults in the ED may help with early intervention for those at high-risk and may improve their prognosis.

The effects of lazaroid U-74389G in a rat sepsis model.

OBJECTIVE AND DESIGN: To examine the protective effects of a lazaroid, 21-aminosteroid U-74389G, in a rat septic shock model. MATERIALS OR SUBJECTS: Male Sprague-Dawley rats (n = 60) aged 6-8 months. TREATMENT: Groups were exposed to 500 cGy radiation followed by E. coli inoculation, and either placebo or lazaroid injection (10 mg/kg intraperitoneal) 5 days after irradiation. METHODS: Hemodynamic measurements, arterial blood gases, serum lactate, total antioxidative capacity, and cytokine levels were measured at specific time intervals. RESULTS: Treatment with the lazaroid U-74389G maintained cardiac output and mean aortic pressure. Lazaroid treatment also prevented the increase in serum lactate seen in placebo-treated rats. Cytokine serum levels in lazaroid-treated rats were not significantly different from those in placebo-treated rats at any time point. CONCLUSIONS: Lazaroid treatment of E. coli-inoculated septic animals lessens the hemodynamic deterioration seen in sepsis.

Effects of epinephrine on heart rate variability and cytokines in a rat sepsis model.

Catecholamines have both anti-inflammatory and vasoactive properties. A decreased cardiac response to catecholamines has been associated with a high risk of death in sepsis and septic shock. The aim of this study was to investigate the effects of epinephrine (EPI) on heart rate variability (HRV) and autonomic balance, as well as cytokine levels, in a rat sepsis model. Thirty-six male Sprague-Dawley rats were assigned to 4 experimental groups and 2 control groups of 6 rats each. The rats in the experimental groups were inoculated with a lipopolysaccharide (LPS, endotoxin) to establish a sepsis model. Group A received only LPS; group B received LPS, antecedent EPI and the nonselective ß-blocker propranolol; group C received LPS and antecedent EPI; and group D received LPS, antecedent EPI and the selective ß1-blocker esmolol. One control group received EPI and the other received saline placebo. Heart rate variability (HRV) was analyzed and tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1ß (IL-1ß) levels were measured. Measurements were carried out at baseline, at 0 hour after EPI infusion, and at 0.5, 2, and 4 hours after LPS inoculation. There were significant differences in HRV and cytokine levels between the groups, indicating that LPS infusion caused autonomic imbalance. Antecedent EPI significantly decreased the level of TNF-α in group C compared with group A in which TNF-α level peaked at 2 hours and then declined. Propranolol (group B) but not esmolol (group D) administration resulted in elevated TNF-α levels, comparable to those observed in group A. In conclusion, antecedent administration of EPI in a rat sepsis model inhibits the production of TNF-α possibly via the ß2-adrenoceptor.

Epinephrine reduces cerebral perfusion during cardiopulmonary resuscitation.

OBJECTIVE: Epinephrine has been the primary drug for cardiopulmonary resuscitation (CPR) for more than a century. The therapeutic rationale was to restore threshold levels of myocardial and cerebral blood flows by its alpha1 (alpha1) and alpha2 (alpha2)-adrenergic agonist vasopressor actions. On the basis of coincidental observations on changes in microvascular flow in the cerebral cortex, we hypothesized that epinephrine selectively decreases microvascular flow. DESIGN: Randomized prospective animal study. SETTING: University-affiliated research laboratory. SUBJECTS: Domestic pigs. INTERVENTIONS: Four groups of five male domestic pigs weighing 40 +/- 3 kg were investigated. After induction of anesthesia, endotracheal intubation was followed by mechanical ventilation. A frontoparietal bilateral craniotomy was created. Ventricular fibrillation was induced and untreated for 3 minutes before the start of precordial compression, mechanical ventilation, and attempted defibrillation. Animals were randomized to receive central venous injections during CPR of 1) placebo, 2) epinephrine, 3) epinephrine in which both alpha1- and beta (beta)-adrenergic effects were blocked by previous administration of prazosin and propranolol, and 4) epinephrine in which both alpha2- and beta-adrenergic effects were blocked by previous administration of yohimbine and propranolol. MEASUREMENTS AND MAIN RESULTS: Cerebral cortical microcirculatory blood flow (MBF) was measured with orthogonal polarization spectral imaging. Cerebral cortical carbon dioxide and oxygen tensions (Pbco2 and Pbo2) were concurrently measured using miniature tissue optical sensors. Each animal was resuscitated. No differences in the number of electrical shocks for defibrillation or in the duration of CPR preceding return of spontaneous circulation were observed. Yet when epinephrine induced increases in arterial pressure, it significantly decreased Pbo2 tension and increased Pbco2 tension. Epinephrine therefore significantly decreased MBF and increased indicators of cerebral ischemia. Reduced MBF and magnified brain tissue ischemia during and after cardiopulmonary resuscitation were traced to the alpha1-adrenergic agonist action of epinephrine. When the alpha2 effects of epinephrine were blocked, reduced MBF and tissue ischemia persisted. No differences in cardiac output, end tidal Pco2, arterial Po2 and Pco2, and brain temperature were observed before inducing cardiac arrest and following return of spontaneous circulation. CONCLUSIONS: In this model, epinephrine through its alpha1-agonist action had adverse effects on cerebral microvascular blood flow such as to increase the severity of cerebral ischemia during CPR.

Aichi Virus Induces Antiviral Host Defense in Primary Murine Intestinal Epithelial Cells.

The picornavirus Aichi virus (AiV) is a non-enveloped RNA virus that causes acute gastroenteritis symptoms, such as diarrhea, abdominal pain, nausea, vomiting, and fever. Antiviral host defense involves the fast response of type I interferon (IFN) and the secretion of inflammatory cytokines against pathogens. However, the intestinal inflammatory and antiviral response to AiV infection is poorly understood. This study evaluated the antiviral activity of intestinal epithelial cells (IECs), which form a single-cell layer separating the bowel wall from pathogens. Isolated primary mouse IECs were subjected to AiV infection and virion production, inducing the mRNA expression of type I/type III IFNs and inflammatory cytokines. The mechanism involved induced the expression of phospho-IFN regulatory factor 3 and mitochondrial antiviral-signaling protein of type I IFN signaling. These findings were also observed in AiV-infected human colon carcinoma cells. In summary, a viral productive and pathogenic infection of AiV in primary murine IECs is validated.

Exclusion of a patient assessment interval and extension of the CPR interval both mitigate post-resuscitation myocardial dysfunction in a swine model of cardiac arrest.

AIM OF STUDY: Interruptions in cardiopulmonary resuscitation (CPR), particularly as guided by automated external defibrillators, have been implicated in poor survival from cardiac arrest. Interruptions of CPR may be reduced by eliminating repetition of shocks between periods of CPR, elimination of the interval for patient assessment before CPR, and extension of the periods of CPR. MATERIALS AND METHODS: The effects of exclusion of a 30s post-shock assessment interval prior to CPR and use of a longer interval (180s versus 90s) of CPR on resuscitation and post-resuscitation function were assessed in a factorial design using an established swine model of cardiac arrest. Repetitive shocks were excluded. Ventricular fibrillation was induced ischemically and maintained untreated for 5min. RESULTS: All subjects were resuscitated, 95% survived 3 days, and 97% of survivors had full neurological recovery. Exclusion of the assessment interval reduced the delay to first return of spontaneous circulation by 33.1s (P=0.004) and the delay to sustained resuscitation by 99.2s (P=0.004), reduced post-resuscitation ECG ST elevation by 0.12mV (P=0.03), and alleviated transient post-resuscitation ejection fraction reduction (P<0.0001). Extension of the CPR interval reduced transient post-resuscitation fractional area change impairment (P=0.003). CONCLUSIONS: Exclusion of an interval for assessment of airway, breathing and signs of circulation mitigates post-resuscitation dysfunction in a swine model of cardiac arrest. Extension of the period of CPR independently provides measurable, though less comprehensive, mitigation as well.

Idiopathic Pulmonary Arterial Hypertension Was Diagnosed Initially by the Computed Tomographic Angiogram.

Idiopathic pulmonary arterial hypertension (IPAH) is a rare and progressive disease with non-specific signs and symptoms. A 50-year-old woman with IPAH presented to the emergency department (ED) with a complaint of episodic dyspnea that had persisted for the previous two months. Based on the fi ndings of the initial chest computed tomographic angiography conducted in the ED, we suspected pulmonary hypertension. IPAH was eventually confi rmed following a series of investigations, including right heart catheterization. The history of this interesting case is reported with a review of the relevant literature.

One-shock versus three-shock defibrillation protocol significantly improves outcome in a porcine model of prolonged ventricular fibrillation cardiac arrest.

BACKGROUND: The success of resuscitation with a 1-shock versus the conventional 3-shock defibrillation protocol was investigated subject to the range of treatment variation imposed by automated external defibrillators (AEDs). METHODS AND RESULTS: Ventricular fibrillation was induced in 44 domestic pigs. After 7 minutes of untreated VF, animals were randomized among 4 groups representing all combinations of the 1- versus 3-shock protocol and 2 different AED regimens (AED1, AED2). Because few AEDs support a 1-shock protocol, manual defibrillators were used to replicate the AED treatment regimen: electrical waveform, dose sequence, and cardiopulmonary resuscitation (CPR) interruption intervals. Initial shock(s) were delivered, followed by 60 seconds of CPR, and the treatment was repeated until resuscitation was successful or for 15 minutes. The 1-shock protocol was associated with improved outcome, reducing CPR interruptions from 45% to 34% of total resuscitation time (P=0.019) and increasing survival from 64% to 100% (P=0.004). Survival was 91% for AED1 versus 36% for AED2 (P=0.024) with a 3-shock protocol but was increased to 100% for both by adoption of a 1-shock protocol. Improvements in postresuscitation left ventricular ejection fraction and stroke volume were observed with AED1 compared with AED2 (difference of means, 15% and 28% of baseline respectively, P<0.001) regardless of defibrillation protocol. CONCLUSIONS: Adoption of a 1-shock versus a 3-shock resuscitation protocol improved survival and minimized outcome differences imposed by variations in AED design and implementation. When a conventional 3-shock defibrillation protocol was used, however, the choice of AED had a significant impact on resuscitation outcome.

The quality of chest compressions during cardiopulmonary resuscitation overrides importance of timing of defibrillation.

BACKGROUND: We address the quality of chest compressions and the impact on initial defibrillation or initial chest compressions after sudden death. METHODS: Ventricular fibrillation was induced by occlusion of the left anterior descending coronary artery in 24 domestic pigs with a mean (+/- SD) weight of 40 +/- 2 kg. Cardiac arrest was left untreated for 5 min. Animals were then randomized to receive chest compressions-first or defibrillation-first and were further randomized to "optimal" or "conventional" chest compressions. A total of four groups of animals were investigated using a factorial design. For optimal chest compressions, the anterior posterior diameter of the chest was reduced by 25%, representing approximately 6 cm. Only 70% of this depth, or approximately 4.2 cm, represented conventional chest compressions. Chest compressions were delivered with a mechanical chest compressor. Defibrillation was attempted with a single biphasic 150-J shock. Postresuscitation myocardial function was echocardiographically assessed. RESULTS: Coronary perfusion pressures and end-tidal Pco(2) were significantly lower with conventional chest compressions. With optimal chest compressions, either as an initial intervention or after defibrillation, each animal was successfully resuscitated. Fewer shocks were required prior to the return of spontaneous circulation after initial optimal chest compressions. No animals were resuscitated when conventional chest compressions preceded the defibrillation attempt. When defibrillation was attempted as the initial intervention followed by conventional chest compressions, two of six animals were resuscitated. CONCLUSIONS: In this animal model of cardiac arrest, it was the quality of the chest compressions, rather then the priority of either initial defibrillation or initial chest compressions, that was the predominant determinant of successful resuscitation.

A comparison of electrically induced cardiac arrest with cardiac arrest produced by coronary occlusion.

OBJECTIVE: The present study was undertaken to compare an animal model of electrically induced VF with ischemically induced VF. In a preponderance of models of cardiac arrest and resuscitation in intact animals, ventricular fibrillation (VF) is induced by an alternating current delivered directly to the epicardium or endocardium. Yet, the applicability of such animal models has been challenged for it is not an electrical current alone but rather a current generated in the ischemic myocardium that triggers VF. Accordingly, a potentially more clinically relevant model was investigated in which spontaneous VF followed acute myocardial ischemia. METHODS: Twenty anesthetized pigs were randomized to either electrical fibrillation or myocardial ischemia following transient occlusion of the left anterior descending (LAD) coronary artery. RESULTS: VF was untreated for 7 min in both models after which mechanical ventilation and precordial compression were begun. Defibrillation was attempted after 5 min of CPR in both groups. VF appeared within 5.7+/-2.0 min of LAD occlusion. CONCLUSIONS: A significant increase in the number of post-resuscitation premature ventricular beats and recurrent VF followed ROSC and a significantly greater number of shocks was required for restoration of spontaneous circulation (ROSC) after LAD occlusion. Nevertheless, early post-resuscitation myocardial dysfunction, neurological recovery and 72 h survival were indistinguishable between the two models.

Disseminated Nocardiosis with Lung, Liver and Spleen Abscesses in Sweet Syndrome: A Case Report.

Hepatic abscesses are rarely encountered in disseminated nocardia infections. We report a rare case of idiopathic Sweet syndrome (SS) who responded well to steroid therapy. However, he developed multiple abscesses in the lung, liver and spleen after 6 months of systemic steroid therapy. The culture result from liver abscess and sputum was diagnostic of disseminiated nocardiosis. Intravenous sulfamethoxazole/trimethoprim was given and follow-up computed tomography (CT) scan revealed resolution of abscess. To conclude, nocardiosis should be suspected as a likely cause of lung, liver and spleen abscesses in patients undergoing long-term steroid treatment. A high index of clinical suspicion in patients with defects in cell-mediated immunity and prompt management by appropriate image studies are needed to prevent delay in diagnosis.

Cardiopulmonary resuscitation in a rat model of chronic myocardial ischemia.

Our group has developed a rat model of cardiac arrest and cardiopulmonary resuscitation (CPR). However, the current rat model uses healthy adult animals. In an effort to more closely reproduce the event of cardiac arrest and CPR in humans with chronic coronary disease, a rat model of coronary artery constriction was investigated during cardiac arrest and CPR. Left coronary artery constriction was induced surgically in anesthetized, mechanically ventilated Sprague-Dawley rats. Echocardiography was used to measure global cardiac performance before surgery and 4 wk postsurgery. Coronary constriction provoked significant decreases in ejection fraction, increases in left ventricular end-diastolic volume, and increases left ventricular end-systolic volume at 4 wk postintervention, just before induction of ventricular fibrillation (VF). After 6 min of untreated VF, CPR was initiated on three groups: 1) coronary artery constriction group, 2) sham-operated group, and 3) control group (without preceding surgery). Defibrillation was attempted after 6 min of CPR. All the animals were resuscitated. Postresuscitation myocardial function as measured by rate of left ventricular pressure increase at 40 mmHg and the rate of left ventricular pressure decline was more significantly impaired and left ventricular end-diastolic pressure was greater in the coronary artery constriction group compared with the sham-operated group and the control group. There were no differences in the total shock energy required for successful resuscitation and duration of survival among the groups. In summary, this rat model of chronic myocardial ischemia was associated with ventricular remodeling and left ventricular myocardial dysfunction 4 wk postintervention and subsequently with severe postresuscitation myocardial dysfunction. This model would suggest further clinically relevant investigation on cardiac arrest and CPR.

Microvascular blood flow during cardiopulmonary resuscitation is predictive of outcome.

There is growing evidence that microcirculatory blood flow is the ultimate determinant of the outcome in circulatory shock states. We therefore examined changes in the microcirculation accompanying the most severe form of circulatory failure, namely cardiac arrest and the effects of subsequent cardiopulmonary resuscitation. Ventricular fibrillation was electrically induced in nine pigs and untreated for 5min prior to beginning closed chest cardiac compression and attempting electrical defibrillation. Orthogonal polarization spectral imaging was utilized for visualization of the sublingual microcirculation at baseline, 0.5, 1, 3 and 5min after onset of ventricular fibrillation and at 1 and 5min after start of chest compression. Images were also obtained 1 and 5min after restoration of spontaneous circulation. Microvascular flow was graded from 0 (no flow) to 3 (normal flow). Aortic and right atrial pressures were measured and coronary perfusion pressure was computed continuously. Microcirculatory blood flow decreased to less than one-fourth within 0.5min after inducing ventricular fibrillation. Precordial compression partially restored microvascular flow in each animal. In animals that were successfully resuscitated, microvascular flow was significantly greater after 1 and 5min of chest compression than in animals with failed resuscitation attempts. Microvascular blood flow was highly correlated with coronary perfusion pressure (r=0.82, p<0.01). Microvascular blood flow in the sublingual mucosa is therefore closely related to coronary perfusion pressure during cardiopulmonary resuscitation and both are predictive of outcome.

A rare but potentially lethal case of tuberculous aortic aneurysm presenting with repeated attacks of abdominal pain.

Tuberculous aortic aneurysm is an extremely rare disease with a high mortality rate. The clinical features of this condition are highly variable, ranging from asymptomatic with or without constitutional symptoms, abdominal pain to frank rupture, bleeding and shock. We herein report the case of a 56-year-old man with a large tuberculous mycotic aneurysm in the abdominal aorta with an initial presentation of repeated attacks of abdominal pain lasting for several months. Due to the vague nature of the initial symptoms, tuberculous aortic aneurysms may take several months to diagnose. This case highlights the importance of having a high index of suspicion and providing timely surgery for this rare but potentially lethal disease.