Detection of Rickettsia spp. and Anaplasma ovis in Melophagus ovinus from southern Xinjiang, China.

Melophagus ovinus is a hematophagous insect that is distributed worldwide and plays a crucial role in transmitting disease-causing pathogens. From June 2021 to March 2022, a total of 370 M. ovinus were collected from 11 sampling points in southern Xinjiang, China. The specimens were identified using morphological and molecular analyses. Rickettsia spp. and Anaplasma ovis were detected from all the samples using seven Rickettsia-specific genetic markers and the msp-4 gene of A. ovis. Approximately 11% of the M. ovinus specimens were positive for Rickettsia spp., and Candidatus Rickettsia barbariae was the most predominant species (35/41; 85.4%), while R. massiliae was least prevalent (6/41; 14.6%). Approximately 10.5% (39/370) of the M. ovinus specimens were positive for A. ovis of genotype III, which was co-detected with Candidatus R. barbariae in M. ovinus (3/370; 0.8%). To the best of our knowledge, this is the first report of the detection of R. massiliae and Candidatus R. barbariae in M. ovinus globally. The detection and control of insect-borne diseases originating from M. ovinus should be strengthened in southern Xinjiang, an area important to animal husbandry and production.

Targeted Temperature Management Suppresses Hypoxia-Inducible Factor-1α and Vascular Endothelial Growth Factor Expression in a Pig Model of Cardiac Arrest.

BACKGROUND: The hypoxia-inducible factor-1α (HIF-1α)/vascular endothelial growth factor (VEGF)/VEGF receptor subtype 2 (VEGFR-2) pathway has been implicated in ischemia/reperfusion injury. The aim of this study was to clarify whether whole-body hypothermic targeted temperature management (HTTM) inhibits the HIF-1α/VEGF/VEGFR-2 pathway in a swine model of cardiac arrest (CA) and cardiopulmonary resuscitation (CPR). METHODS: Twenty-four domestic male Beijing Landrace pigs were used in this study. CA was electrically induced with ventricular fibrillation and left untreated for 8 min. Return of spontaneous circulation (ROSC) was achieved in 16 pigs, which were randomly assigned either to normothermia at 38 °C or to HTTM at 33 °C (each group: n = 8). HTTM was intravascularly induced immediately after ROSC. The core temperature was reduced to 33 °C and maintained for 12 h after ROSC. The serum levels of HIF-1α, VEGF, VEGFR-2, and neuron-specific enolase (NSE) were measured with enzyme immunoassay kits 0.5, 6, 12, and 24 h after ROSC. The expression of HIF-1α, VEGF, and VEGFR-2 in cerebral cortical tissue was measured by RT-PCR and Western blot analysis 24 h after ROSC. Neurological deficit scores and brain cortical tissue water content were evaluated 24 h after ROSC. RESULTS: The serum levels of HIF-1α, VEGF, and VEGFR-2 were significantly increased under normothermia within 24 h after ROSC. However, these increases were significantly reduced by HTTM. HTTM also decreased cerebral cortical HIF-1α, VEGF, and VEGFR-2 mRNA and protein expression 24 h after ROSC (all p < 0.05). HTTM pigs had better neurological outcomes and less brain edema than normothermic pigs. CONCLUSION: The HIF-1α/VEGF/VEGFR-2 system is activated following CA and CPR. HTTM protects against cerebral injury after ROSC, which may be part of the mechanism by which it inhibits the expression of components of the HIF-1α/VEGF/VEGFR-2 signaling pathway.

Changes of Endothelin-1 and Nitric Oxide Systems in Brain Tissue During Mild Hypothermia in a Porcine Model of Cardiac Arrest.

BACKGROUND: Our previous study found that mild hypothermia (MH) after resuscitation reduced cerebral microcirculation, but the mechanism was not elucidated. The aim of this study was to clarify changes of endothelin-1 (ET-1) and nitric oxide (NO) systems in brain tissue during hypothermia after resuscitation. METHODS: Twenty-six domestic male Beijing Landrace pigs were used in this study. MH was intravascularly induced 1 h after resuscitation from 8-min ventricular fibrillation. Core temperature was reduced to 33 °C and maintained until 8 h after resuscitation, and then animals were euthanized. ET-1 and NO levels in brain tissue and peripheral plasma were measured. Expression of endothelin-converting enzyme-1 (ECE-1), endothelin A receptor (ET-AR), endothelin-B receptor, and nitric oxide synthase (NOS) in brain tissue was determined by Western blot analysis. RESULTS: Compared with non-hypothermia (NH) treatment, MH after resuscitation significantly increased the level of endothelin-1 and reduced the level of NO in peripheral blood and brain tissue. Cerebral expression of ECE-1 and ET-AR was significantly increased during MH after resuscitation. Moreover, MH significantly decreased inducible NOS expression compared with the NH group. CONCLUSIONS: The ET-1 system is activated, while inducible NOS is inhibited in brain tissue during MH after resuscitation.

Selective beta-blocker esmolol improves cerebral cortex microcirculation in a swine ventricular fibrillation model.

OBJECTIVE: This study aimed to identify whether esmolol attenuates cerebral cortex microcirculation blood flow due to epinephrine in prolonged ventricular fibrillation (VF) and cardiopulmonary resuscitation (CPR), and may improve neurological prognosis. METHODS: Male pigs were randomized into the esmolol+epinephrine group (group EE), the epinephrine group (group EP), and the normal saline group (group NS) (n = 8 each group). Untreated VF for 8 minutes was induced in pigs. After CPR for 2 minutes, group EE received esmolol (500 µg/kg)+epinephrine (20 µg/kg), group EP received epinephrine 20 µg/kg, and group NS received 5 mL normal saline. Then, a 120 J electric shock was delivered. If the return of spontaneous circulation (ROSC) failed, epinephrine (20 µg/kg) was repeated in group EP and EE, followed by another 2 minutes of CPR, a 150 J electric shock was delivered every 2 minutes until ROSC. Cerebral microcirculation images were obtained at 0.5, 6, 12, and 24 hours by cranial windows after ROSC. Cerebral performance category scores and neurological deficit scores (NDS) were calculated. The frontal cortices were harvested after the animals were euthanized. RESULTS: The NDS, the perfused vessel density, and the microcirculatory flow index of group EE were better than other two groups. The morphology of endothelial cells in the group EE remained intact; however, it was destroyed in the group EP. CONCLUSIONS: Administration of esmolol with epinephrine may alleviate the impairment of cerebral microcirculation blood flow caused by the administration of epinephrine in prolonged VF and thereby improves neurological outcomes in a swine model.

Genetic Diversity of Echinococcus granulosus Genotype G1 in Xinjiang, Northwest of China.

Cystic echinococcosis (CE) caused by E. granulosus is a serious helminthic zoonosis in humans, livestock and wildlife. Xinjiang is one of high endemic province for CE in China. A total of 55 sheep and cattle livers containing echinococcal cysts were collected from slaughterhouses in Changji and Yining City, northern region of Xinjiang. PCR was employed for cloning 2 gene fragments, 12S rRNA and CO1 for analysis of phylogenetic diversity of E. granulosus. The results showed that all the samples collected were identified as G1 genotype of E. granulosus. Interestingly, YL5 and CJ75 strains were the older branches compared to those strains from France, Argentina, Australia. CO1 gene fragment showed 20 new genotype haploids and 5 new genotype haplogroups (H1-H5) by the analysis of Network 5.0 software, and the YLY17 strain was identified as the most ancestral haplotype. The major haplotypes, such as CJ75 and YL5 strains, showed identical to the isolates from Middle East. The international and domestic trade of livestock might contribute to the dispersal of different haplotypes for E. granulosus evolution.

Therapeutic hypothermia attenuates brain edema in a pig model of cardiac arrest: Possible role of the angiopoietin-Tie-2 system.

OBJECTIVE: This study aimed to clarify whether therapeutic hypothermia protects against cerebral edema following cardiac arrest (CA) and cardiopulmonary resuscitation (CPR) in a porcine model via regulating the angiopoietin-Tie-2 ligand-receptor system. METHODS: Male pigs were randomized into the therapeutic hypothermia group, the normothermia group or the sham control group. CA was induced in pigs by untreated ventricular fibrillation for 8min. Brain edema was determined by measuring the cerebral cortical water content at 24h after the return of spontaneous circulation (ROSC). The serum levels of angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), tyrosine kinase with immunoglobulin-like loop epidermal growth factor homology domain 2 (Tie-2), and S100B were measured using enzyme immunoassay kits at 0.5, 6, 12 and 24h after ROSC. The levels of the Ang-1, Ang-2, phosphorylated Tie-2 and Tie-2 proteins in the cerebral cortex at 24h after ROSC were determined by Western blotting. RESULTS: Therapeutic hypothermia lessened brain cortex edema, alleviated histopathology injury, and improved neurologic outcomes at 24h after ROSC. Therapeutic hypothermia inhibited the CA- and CPR-induced increases in serum Ang-2 protein expression and the Ang-2/Ang-1 ratio and attenuated the decrease in serum Ang-1 expression. Therapeutic hypothermia also increased the protein expression of Ang-1 and the phosphorylated Tie-2/Tie-2 ratio and inhibited the expression of Ang-2 in the cerebral cortex at 24h after ROSC. CONCLUSIONS: Based on our experiment, therapeutic hypothermia decreased cerebral edema after CA, which may be, at least in part, related to its ability to modulate the expression of components of the Ang-Tie-2 system.

Comparison of early sequential hypothermia and delayed hypothermia on neurological function after resuscitation in a swine model.

BACKGROUND: We utilized a porcine cardiac arrest model to compare early sequential hypothermia (ESH) with delayed hypothermia (DH) and no hypothermia (NH) to investigate the different effects on cerebral function after resuscitation. METHODS: After return of spontaneous circulation (ROSC), resuscitated 24 pigs divided into three groups. The ESH group implemented early sequential hypothermia immediately, and the DH group implemented delayed hypothermia at 1 h after ROSC. The core temperature, hemodynamic parameters and oxygen metabolism were recorded. Cerebral metabolism variables and neurotransmitter in the extracellular fluid were collected through the microdialysis tubes. The bloods were analyzed for venous jugular bulb oxygen saturation, lactate and neuron specific nolase. The cerebral function was evaluated using the cerebral performance category and neurologic deficit score at 72h after ROSC and cerebral histology in the right posterior frontal lobe were collected. RESULTS: ESH reached the target temperature earlier and showed more favorable outcomes of neurological function than DH. Specifically, early sequential hypothermia reduced cerebral oxygen and energy consumption and decreased extracellular accumulation of neurotransmitters after resuscitation and protected the integrity of the BBB during reperfusion. CONCLUSIONS: Early sequential hypothermia could increase the protection of neurological function after resuscitation and produce better neurological outcomes. The institutional protocol number: 2010-D-013.

Effects of Mild Hypothermia on Cerebral Large and Small Microvessels Blood Flow in a Porcine Model of Cardiac Arrest.

BACKGROUND: The effect of mild hypothermia (MH) on microcirculation after resuscitation from cardiac arrest is controversial. The aim of this study was to determine whether MH improves or aggravates the disturbance of cerebral microcirculation. METHODS: Twenty domestic male pigs were randomized into the MH group (n = 8), non-hypothermia (NH) group (n = 8) or sham operation group (n = 4). In the MH group, the animals were initiated rapid intravascular cooling at 1 h after return of spontaneous circulation (ROSC) from 8 min ventricular fibrillation, and the core temperature was reduced to 33 °C for 12 h and then rewarmed to 37 °C. In the NH group, animals did not receive hypothermia treatment after ROSC. In the sham operation group, the same surgical procedure was performed, but without inducing ventricular fibrillation and hypothermia treatment. The cerebral microvascular flow index (MFI) of large microvessel (diameter > 20 µm) and small microvessel (diameter < 20 µm) was measured after ROSC. Cerebral oxygen extraction ratio, internal jugular venous-artery lactate difference, and CO2 difference were also calculated. RESULTS: Cerebral MFI dramatically reduced after ROSC, and MH further aggravated the decrease in MFI of small microvessel compared with NH (p < 0.05). Internal jugular venous-arterial lactate difference and CO2 difference, and oxygen extraction ratio were all significantly increased after ROSC. MH significantly decreased the values compared with NH (p < 0.05). CONCLUSIONS: MH decreases cerebral small microvessel blood flow and cerebral metabolism after ROSC compared with NH. However, the total effect is that cerebral oxygen supply-demand relationship is improved during hypothermia.

Phosphodiesterase-5 inhibition improves macrocirculation and microcirculation during cardiopulmonary resuscitation.

AIM: This study is to clarify whether sildenafil, which is a selective inhibitor of the isoform 5 of the enzyme phosphodiesterase, improves macrocirculation or/and microcirculation during ventricular fibrillation (VF) and cardiopulmonary resuscitation (CPR) so as to improve outcomes of resuscitation. METHODS: Sixteen female pigs were used. After anesthesia, the abdominal cavity was opened to observe the mesenteric microcirculation. Following the guidelines, we determined microvascular flow index, perfused vessel density and proportion of perfused vessels both for large(diameter >20 µm)and small (diameter <20 µm) microvessels. Sildenafil (0.5 mg/kg) or saline was given at 30 minutes before inducing VF. After 8 min VF, 4 min CPR was started and then defibrillation was attempted. RESULTS: Compared with saline, sildenafil reduced the shocks and duration of CPR (all P < .05), and improved coronary perfusion pressure (CPP) during CPR and 24-hour survival (all P < .05). Sildenafil significantly improved microcirculatory parameters in large microvessel and decreased the lactic acid level during VF and CPR (all P < .05), but the differences in small microvessel were not significant (all P > .05). Microvascular flow index in both large and small microvessels were closely correlated to each other (r = 0.91, P < .01), and to CPP during CPR ([r = .88, P < .01] and [r = .70, P < .05], respectively). CONCLUSION: Sildenafil increases the success of resuscitation through improving macrocirculation and microcirculation during VF and CPR. There is a close relationship between microvascular flow and CPP during CPR.

The effects of phosphodiesterase-5 inhibitor sildenafil against post-resuscitation myocardial and intestinal microcirculatory dysfunction by attenuating apoptosis and regulating microRNAs expression: essential role of nitric oxide syntheses signaling.

BACKGROUND: Recent experimental and clinical studies have indicated the cardioprotective role of sildenafil during ischemia/reperfusion (I/R) injury. Sildenafil has been shown to attenuate postresuscitation myocardial dysfunction in piget models of ventricular fibrillation. This study was designed to investigate if administration of sildenafil will attenuate post-resuscitation myocardial dysfunction by attenuating apoptosis and regulating miRNA expressions, furthermore, ameliorating the severity of post-microcirculatory dysfunction. METHODS: Twenty-four male pigs (weighing 30 ± 2 kg) were randomly divided into groups, sildenafil pretreatment (n = 8), saline (n = 8) and sham operation (sham, n = 8). Sildenafil pretreatment consisted of 0.5 mg/kg sildenafil, administered once intraperitoneally 30 min prior to ventricular fibrillation (VF). Eight minutes of untreated VF was followed by defibrillation in anesthetized, closed-chest pigs. Hemodynamic status and blood samples were obtained at 0 min, 0.5, 1, 2, 4 and 6 h after return of spontaneous circulation (ROSC). Surviving pigs were euthanatized at 24 h after ROSC, and hearts were removed for analysis by electron microscopy, western blotting, quantitative real-time polymerase chain reaction (PCR), and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. Intestinal microcirculatory blood flow was visualized by a sidestream dark-field imaging device at baseline and 0.5, 1, 2, 4, and 6 h after ROSC. RESULTS: Compared with the saline group, the sildenafil group had a higher 24-hour survival (7/8 versus 3/8 survivors, p < 0.05) and a better outcome in hemodynamic parameters. The protective effect of sildenafil also correlated with reduced cardiomyocyte apoptosis, as evidenced by reduced TUNEL-positive cells, increased anti-apoptotic Bcl-2/Bax ratio and inhibited caspase-3 activity in myocardium. Additionally, sildenafil treatment inhibited the increases in the microRNA-1 levels and alleviated the decreases in the microRNA-133a levels which negatively regulates pro-apoptotic genes. At 6 h after ROSC, post-resuscitation perfused vessel density and microcirculatory flow index were significantly lower in the saline group than in the sildenafil group. CONCLUSIONS: The major findings of this study are as follows: (1) sildenafil improved post-resuscitation perfusion of the heart, and thus reduced cardiac myocyte apoptosis and improved cardiac function; (2) sildenafil treatment inhibited the increases in the microRNA-1 levels, but alleviated the decreases in the microRNA-133a levels.

Molecular detection of hepatitis E virus in sheep from southern Xinjiang, China.

Hepatitis E virus (HEV) is a causative agent of infectious hepatitis in animals and humans both in developing and developed countries. Here, we collected 500 sheep sera and 75 raw sheep liver samples from a slaughterhouse in the southern part of the Xinjiang region, China, along with 26 sera of butchers from the same slaughterhouse. All serum samples were tested for anti-HEV antibody by enzyme-linked immunosorbent assay. Both serum and liver samples were evaluated for the presence of HEV RNA by nested polymerase chain reaction targeting partial nucleotide sequences of open reading frame 2 (ORF2). The results indicate that sheep seroprevalence was 35.20 % (176/500) and that four of the 75 (5.3 %) sheep livers showed detectable amounts of HEV RNA. The seroprevalence of the butchers was 57.7 % (15/26). The four amplicons shared 97.8-100 % nucleotide sequence identity and had pairwise sequence identities of 81.6-85.3 %, 84.2-85.3 %, 82.1-85.3 % and 84.7-97.9 % with the corresponding regions of genotypes 1, 2, 3 and 4 of HEV, respectively. A phylogenetic tree was constructed based on alignments of an amplified 186-bp ORF2 sequence and corresponding reference strains. The analysis showed that the four sheep strains detected in our study formed a lineage within a genotype 4 cluster that contains hb-3, bjsw1, T1, swCH189 and swCH25, all of which belong to genotype 4, subtype 4d. The results indicated a high level of seroconversion in sheep and suggested that sheep liver may be a source of foodborne HEV infection in humans.

Sildenafil Protects against Myocardial Ischemia-Reperfusion Injury Following Cardiac Arrest in a Porcine Model: Possible Role of the Renin-Angiotensin System.

Sildenafil, a phosphodiesterase-5 inhibitor sold as Viagra, is a cardioprotector against myocardial ischemia/reperfusion (I/R) injury. Our study explored whether sildenafil protects against I/R-induced damage in a porcine cardiac arrest and resuscitation (CAR) model via modulating the renin-angiotensin system. Male pigs were randomly divided to three groups: Sham group, Saline group, and sildenafil (0.5 mg/kg) group. Thirty min after drug infusion, ventricular fibrillation (8 min) and cardiopulmonary resuscitation (up to 30 min) was conducted in these animals. We found that sildenafil ameliorated the reduced cardiac function and improved the 24-h survival rate in this model. Sildenafil partly attenuated the increases of plasma angiotensin II (Ang II) and Ang (1-7) levels after CAR. Sildenafil also decreased apoptosis and Ang II expression in myocardium. The increases of expression of angiotensin-converting-enzyme (ACE), ACE2, Ang II type 1 receptor (AT1R), and the Ang (1-7) receptor Mas in myocardial tissue were enhanced after CAR. Sildenafil suppressed AT1R up-regulation, but had no effect on ACE, ACE2, and Mas expression. Sildenafil further boosted the upregulation of endothelial nitric oxide synthase (eNOS), cyclic guanosine monophosphate (cGMP) and inducible nitric oxide synthase(iNOS). Collectively, our results suggest that cardioprotection of sildenafil in CAR model is accompanied by an inhibition of Ang II-AT1R axis activation.

The protective effects of a phosphodiesterase 5 inhibitor, sildenafil, on postresuscitation cardiac dysfunction of cardiac arrest: metabolic evidence from microdialysis.

INTRODUCTION: Recent experimental and clinical studies have indicated the cardioprotective role of sildenafil during ischemia/reperfusion injury. The aim of this study was to determine, by obtaining metabolic evidence from microdialysis, if sildenafil could reduce the severity of postresuscitation myocardial dysfunction and lead to cardioprotection through beneficial effects on energy metabolism. METHODS: Twenty-four male piglets were randomly divided into three groups: sildenafil (n = 8), saline (SA; n = 8) and sham operation (n = 8). Sildenafil pretreatment consisted of 0.5 mg/kg sildenafil administered once intraperitoneally 30 minutes prior to ventricular fibrillation (VF). The myocardial interstitial fluid (ISF) concentrations of glucose, lactate, pyruvate, glutamate and glycerol were determined by microdialysis before VF. Afterward, the piglets were subjected to 8 minutes of untreated VF followed by 15 minutes of open-chest cardiopulmonary resuscitation. ISF was collected continuously, and the experiment was terminated 24 hours after resuscitation. RESULTS: After 8 minutes of untreated VF, the sildenafil group exhibited higher glucose and pyruvate concentrations of ISF and lower lactate and glutamate levels in comparison with the SA group, and these data reached statistical significance (P < 0.05). Advanced cardiac life support was delivered to both groups, with a 24-hour survival rate showing a promising trend in the sildenafil group (7 of 8 versus 3 of 8 survivors, P < 0.05). Compared with the SA group, the sildenafil group had a better outcome in terms of hemodynamic and oxygen metabolism parameters (P < 0.05). Myocardial tissue analysis revealed a dramatic increase in the contents of ATP, ADP and phosphocreatine in the sildenafil group versus the SA group at 24 hours after return of spontaneous circulation (ROSC; P = 0.03, P = 0.02 and P = 0.02, respectively). Furthermore, 24 hours after ROSC, the sildenafil group had marked elevations in activity of left ventricular Na(+)-K(+)-ATPase and Ca(2+)-ATPase compared with the SA group (P = 0.03, P = 0.04, respectively). CONCLUSIONS: Sildenafil could reduce the severity of postresuscitation myocardial dysfunction, and it produced better clearance of metabolic waste in the ISF. This work might provide insights into the development of a novel strategy to treat postresuscitation myocardial dysfunction.

A new method to evaluate carotid blood flow by continuous Doppler monitoring during cardiopulmonary resuscitation in a porcine model of cardiac arrest.

AIM: We used a wearable carotid Doppler patch to study carotid blood flow patterns in a porcine model of cardiac arrest to identify return of spontaneous circulation (ROSC) and hemodynamics associated with different arrhythmias and the quality of compressions. METHODS: Twenty Landrace pigs were used as models of cardiac arrest following a standard protocol. Carotid blood flow was monitored continuously using noninvasive ultrasound. Carotid spectral waveforms were captured during various arrhythmias and CPR. Typical carotid blood flow waveforms were recorded at the time of ROSC, and hemodynamic changes were compared with carotid blood flow parameters. RESULTS: The results showed that the carotid blood flow waveforms varied with ventricular arrhythmia type. During CPR, compression depth correlated significantly with carotid maximal velocity (Vmax) (Spearman correlation coefficient (r) = 0.682, P < 0.001) and velocity-time integral (VTI) (r = 0.794, P < 0.001). Vmax and VTI demonstrated moderate predictive value for survival. The regular carotid blood flow pattern towards the brain was observed during ROSC, concurrent with compression waveforms. After ROSC, VTI and carotid pulse volume (cPV) showed similar trends as stroke volume (SV). The carotid minute volume (cMV) exhibited a similar trend as cardiac output (CO). CONCLUSIONS: Carotid blood flow monitoring could provide valuable information about different arrhythmias as well as the quality of CPR. Carotid flow monitoring allows for timely and effective identification of ROSC. In addition, it may provide valuable hemodynamic information after ROSC.

Evaluation of hemorrhagic shock and fluid resuscitation in pigs using handless Doppler carotid artery ultrasound.

OBJECTIVE: This study aimed to utilize a hemorrhagic shock pig model to compare two hemodynamic monitoring methods, pulse index continuous cardiac output (PiCCO) and spectral carotid artery Doppler ultrasound (CDU). Additionally, we sought to explore the feasibility of employing CDU as a non-invasive hemodynamic monitoring tool in the context of hemorrhagic shock and fluid resuscitation. DESIGN: Animal experiments. SETTING AND SUBJECTS: Female pigs were selected, and hemorrhagic shock was induced by rapid bleeding through an arterial sheath. INTERVENTIONS: Hemodynamic monitoring was conducted using both PiCCO and CDU during episodes of hemorrhagic shock and fluid resuscitation. MEASUREMENTS AND MAIN RESULTS: Among the 10 female pigs studied, CDU measurements revealed a significant decrease in carotid velocity time integral (cVTI) compared to baseline values under shock conditions. During the resuscitation phase, after the mean arterial pressure (MAP) returned to its baseline level, there was no significant difference between cVTI and baseline values. A similar trend was observed for carotid peak velocity (cPV). The corrected flow time (FTc) exhibited a significant difference only at the time of shock compared to baseline values. In comparison to PiCCO, there was a significant correlation between cVTI and MAP (r = 0.616, P < 0.001), stroke volume (SV) (r = 0.821, P < 0.001), and cardiac index (CI) (r = 0.698, P < 0.001). The carotid Doppler shock index (cDSI) displayed negative correlations with MAP (r = - 0.593, P < 0.001), SV (r = - 0.761, P < 0.001), and CI (r = - 0.548, P < 0.001), while showing a positive correlation with the shock index (SI) (r = 0.647, P < 0.001). CONCLUSIONS: Compared to PiCCO, CDU monitoring can reliably reflect the volume status of hemorrhagic shock and fluid resuscitation. CDU offers the advantages of being non-invasive, providing real-time data, and being operationally straightforward. These characteristics make it a valuable tool for assessing and managing hemorrhagic shock, especially in resource-limited settings.

The regulatory effects of serum catecholamines and endothelial cells in pig hemorrhagic shock and fluid resuscitation models.

Background: Acute blood loss not only leads to systemic compensatory response, but also the induced changes in vascular endothelial function.These pathological changes may have potential compensatory significance for maintaining organ perfusion and fluid resuscitation. Objective: To understand trauma-induced endotheliopathy and their compensatory roles in acute hemorrhage, a porcine model of hemorrhagic shock (HS) was used to evaluate changes in vascular endothelial factors and catecholamine levels at different time points from shock to fluid resuscitation. Methods: HS was induced in female pigs by rapid bleeding via the arterial sheath. Hemodynamic monitoring was performed using a pulse index continuous cardiac output (PiCCO) system in HS and fluid resuscitation. Femoral vein blood samples were collected at baseline and 40% mean arterial pressure (MAP, shock), MAP recovery, and 30 min, 1 h, and 2 h after recovery. Serum levels of catecholamine and Angiopoietin-1 (Ang-1), Angiopoietin-2 (Ang-2), Tie-2, Eselectin, intracellular adhesion molecule-1 (ICAM-1), soluble thrombomodulin (sTM), and Syndecan-1 (SDC-1) were evaluated using enzyme-linked immunosorbent assay (ELISA). Results: Serum catecholamine levels were significantly higher in the shock than in the baseline state. Ang-1 and Ang-2 are endothelial growth factors secreted with distinct roles. Ang-1 stabilizes the endothelium and inhibits vascular leakage, and Ang-2 has the opposite effect. The ratio of Ang-2/Ang-1 was significantly higher in the shock state than in the baseline state; however, the Ang-1/Tie-2 ratio was comparable between the two states. This suggests that changes in vascular permeability may mainly depend on the upregulation of Ang-2 function. Serum levels of E-selectin, ICAM-1, sTM, and SDC-1 were significantly higher in the shock state than in the baseline state. After the MAP was restored to the baseline state, the levels of E-selectin, and SDC-1 remained higher compared with the baseline state until 1 h after MAP recovery. Conclusions: serum levels of catecholamines and vascular endothelial markers increased transiently under HS, promoting a compensatory response of the circulatory system to acute bleeding. This may be one of the potential theoretical basis for restrictive fluid resuscitation.

The impact of supplementing vitamin D through different methods on the prognosis of COVID-19 patients: a systematic review and meta-analysis.

Objective: To analyze the impact of different methods of Vitamin D administration on the prognosis of COVID-19 patients. Methods: A comprehensive literature search was conducted across four databases: PubMed, Embase, Web of Science, and Cochrane, up to January 5, 2024. Eligible studies included randomized controlled trials and cohort studies that compared Vitamin D supplementation with control groups in COVID-19 patients. Outcomes of interest were mortality rate, ICU (Intensive Care Unit) admission rate, length of hospital stay, and endotracheal intubation rate. Subgroup analyses were performed based on the dosing regimen (single-dose vs. continuous-dose), total Vitamin D intake within 14 days (≥100,000 IU vs. <100,000 IU), and baseline serum Vitamin D levels (deficient group: 25OHD < 30 ng/mL vs. non-restricted group). A random-effects model was employed for meta-analysis to account for heterogeneity among studies. Results: A total of 21 studies involving 4,553 participants were included. In terms of mortality, Vitamin D supplementation significantly reduced the mortality rate (RR = 0.72, 95% CI: 0.54-0.94, I 2 = 54%, p = 0.02), with continuous dosing being more effective (RR = 0.53, 95% CI: 0.34-0.83, I 2 = 55%, p = 0.006) compared to single-dose (RR = 0.88, 95% CI: 0.69-1.12, I 2 = 21%, p = 0.3), and lower total doses (<100,000 IU) showing greater benefit (RR = 0.30, 95% CI: 0.21-0.44, I 2 = 0%, p < 0.0001). Mortality was significantly reduced in the Vitamin D-deficient group (25OHD < 30 ng/mL) (RR = 0.73, 95% CI: 0.59-0.89, I 2 = 0%, p = 0.002) but not in the non-restricted group. Regarding ICU admission, supplementation reduced ICU admission rates (RR = 0.58, 95% CI: 0.38-0.88, I 2 = 74%, p = 0.01), with continuous dosing (RR = 0.44, 95% CI: 0.22-0.90, I 2 = 74%, p = 0.02) being more effective than single-dose (RR = 0.79, 95% CI: 0.61-1.03, I 2 = 22%, p = 0.08), and lower doses (<100,000 IU) providing more significant reduction (RR = 0.31, 95% CI: 0.21-0.47, I 2 = 0%, p = 0.001). ICU admission rates were significantly reduced in the Vitamin D-deficient group (RR = 0.63, 95% CI: 0.42-0.93, I 2 = 0%, p = 0.02) but not in the non-restricted group (RR = 0.59, 95% CI: 0.32-1.11, I 2 = 86%, p = 0.1). For length of hospital stay, no significant differences were observed between Vitamin D and control groups (MD = -1, 95% CI: -2.16 to 0.16, p = 0.13), and subgroup analyses by dosing regimen, total dose, and baseline Vitamin D levels also showed no significant differences. Similarly, for endotracheal intubation, there was no significant difference in intubation rates between groups (RR = 0.78, 95% CI: 0.56-1.08, p = 0.13), and subgroup analyses confirmed no significant effect of different dosing strategies or baseline Vitamin D status on intubation rates. Conclusion: Vitamin D supplementation improves clinical outcomes in COVID-19 patients by reducing mortality and ICU admission rates, particularly when administered continuously with a total dose of less than 100,000 IU over 14 days, and among those with baseline Vitamin D deficiency (25OHD < 30 ng/mL). However, there were no significant effects on the length of hospital stay or endotracheal intubation rates, regardless of the dosing regimen or baseline Vitamin D levels. These findings emphasize the importance of considering both the total dose over 14 days and baseline Vitamin D status to optimize therapeutic benefits.

Predicting sepsis in-hospital mortality with machine learning: a multi-center study using clinical and inflammatory biomarkers.

BACKGROUND: This study aimed to develop and validate an interpretable machine-learning model that utilizes clinical features and inflammatory biomarkers to predict the risk of in-hospital mortality in critically ill patients suffering from sepsis. METHODS: We enrolled all patients diagnosed with sepsis in the Medical Information Mart for Intensive Care IV (MIMIC-IV, v.2.0), eICU Collaborative Research Care (eICU-CRD 2.0), and the Amsterdam University Medical Centers databases (AmsterdamUMCdb 1.0.2). LASSO regression was employed for feature selection. Seven machine-learning methods were applied to develop prognostic models. The optimal model was chosen based on its accuracy, F1 score and area under curve (AUC) in the validation cohort. Moreover, we utilized the SHapley Additive exPlanations (SHAP) method to elucidate the effects of the features attributed to the model and analyze how individual features affect the model's output. Finally, Spearman correlation analysis examined the associations among continuous predictor variables. Restricted cubic splines (RCS) explored potential non-linear relationships between continuous risk factors and in-hospital mortality. RESULTS: 3535 patients with sepsis were eligible for participation in this study. The median age of the participants was 66 years (IQR, 55-77 years), and 56% were male. After selection, 12 of the 45 clinical parameters collected on the first day after ICU admission remained associated with prognosis and were used to develop machine-learning models. Among seven constructed models, the eXtreme Gradient Boosting (XGBoost) model achieved the best performance, with an AUC of 0.94 and an F1 score of 0.937 in the validation cohort. Feature importance analysis revealed that Age, AST, invasive ventilation treatment, and serum urea nitrogen (BUN) were the top four features of the XGBoost model with the most significant impact. Inflammatory biomarkers may have prognostic value. Furthermore, SHAP force analysis illustrated how the constructed model visualized the prediction of the model. CONCLUSIONS: This study demonstrated the potential of machine-learning approaches for early prediction of outcomes in patients with sepsis. The SHAP method could improve the interoperability of machine-learning models and help clinicians better understand the reasoning behind the outcome.

Effect of rescue breathing during cardiopulmonary resuscitation on lung function after restoration of spontaneous circulation in a porcine model of prolonged cardiac arrest.

OBJECTIVE: The destruction of the pulmonary structure after cardiopulmonary resuscitation may lead to lung function breakdown. The aim of this study was to investigate lung function after cardiopulmonary resuscitation and the influence of rescue breathing on lung function. DESIGN: Prospective, randomized animal study. SETTING: A university animal research laboratory. SUBJECTS: Twenty-eight male domestic pigs weighing 30 ± 2 kg. INTERVENTIONS: The animals were randomized into three groups: continuous compressions (n = 12), 30:2 compression/rescue ventilation cardiopulmonary resuscitation (n = 12), and sham cardiopulmonary resuscitation (n = 4). Ventricular fibrillation was induced in the continuous compressions and compression/rescue ventilation groups. MEASUREMENTS AND MAIN RESULTS: Cardiac output, extravascular lung water, and airway resistance were measured at baseline and 1, 2, and 4 hrs after restoration of spontaneous circulation. Thoracopulmonary compliance, lower inflection point, and dead space were calculated. Lung ventilation/perfusion scans with Tc were performed 48 hrs before the experiment and 24 hrs after restoration of spontaneous circulation. Conventional histopathology evaluation was performed. Dead space, airway resistance, lower inflection point, and extravascular lung water significantly increased and compliance decreased after restoration of spontaneous circulation in the continuous compressions and compression/rescue ventilation groups. Lung injury was more severe in the continuous compressions group. Significant differences were found between the two groups in the three time points after restoration of spontaneous circulation (p < 0.05). Variables of the sham cardiopulmonary resuscitation group remained stable during the whole protocol. Poor ventilation/perfusion and mismatch were found after restoration of spontaneous circulation, but the injury was mitigated in the compression/rescue ventilation group. Histopathology injury in the compression/rescue ventilation group was also improved. CONCLUSIONS: Appropriate rescue breathing during cardiopulmonary resuscitation does not influence the prognosis of cardiac arrest or the hemodynamics after restoration of spontaneous circulation but can improve lung function and alleviate lung injury.

Hemodynamic and catecholamine changes after recurrent ventricular fibrillation.

BACKGROUND: Patients with recurrent ventricular fibrillation (VF) have a high mortality rate, which may be partly due to hemodynamic instability. OBJECTIVES: The aim of this study was to simulate spontaneous recurrent VF by repeated induction of VF in pigs, and to evaluate the subsequent changes in heart rate (HR), blood pressure (BP), and serum catecholamine levels. METHODS: VF was induced four times in each of eight female pigs. Defibrillation was first attempted at 30 s after induction of each episode of VF. Circulation was allowed to stabilize for 30 min after return of spontaneous circulation (ROSC) before induction of the next episode of VF. HR and BP were measured before each induction of VF and at 1 min after each ROSC, and venous blood was drawn at the same times to measure serum catecholamine levels. RESULTS: VF was induced a total of 32 times. Serum epinephrine (EPI) and norepinephrine (NE) levels decreased (p all < 0.05) and dopamine (DA) levels gradually increased (p < 0.05) with repeated episodes of VF. Compared with baseline values before each episode of VF, BP increased significantly at 1 min after ROSC (p all < 0.05) and then gradually returned to baseline values. HR increased significantly after the first ROSC and stayed elevated. No significant correlations were found between catecholamine levels and HR or BP. CONCLUSION: With repeated episodes of VF, BP increased transiently and then gradually returned to baseline values, but HR stayed elevated. Serum DA levels increased, EPI and NE levels gradually decreased.