Sevoflurane Postconditioning Protects From an Early Neurological Deficit After Subarachnoid Hemorrhage: Results of a Randomized Laboratory Study in Rats.

BACKGROUND: Subarachnoid hemorrhage (SAH) is associated with neurocognitive impairment. Recent data suggest that sevoflurane attenuates edema formation after SAH in rats. However, so far, no information is available about the long-term repair phase, nor if sevoflurane impacts functionality by increasing vascularity. This study tested whether sevoflurane postconditioning would improve long-term neurologic deficit through increased formation of new vessels close to the hemorrhage area. METHODS: Fifty-three animals were subjected to SAH or sham surgery with or without a 2-hour sevoflurane postconditioning (versus propofol anesthesia). Animal survival, including dropout animals due to death or reaching termination criteria, as well as neurologic deficit, defined by the Garcia score, were assessed 2 hours after recovery until postoperative day 14. On day 14, blood samples and brain tissue were harvested. Vessel density was determined by the number of cluster of differentiation 31 (CD31)-positive vessels, and activated glial cells by glial fibrillary acidic protein (GFAP)-positive astrocytes per field of view. RESULTS: The survival rate for sham animals was 100%, 69% in the SAH-propofol and 92% in the SAH-sevoflurane groups. According to the log-rank Mantel-Cox test, survival curves were significantly different (P = .024). The short-term neurologic deficit was higher in SAH-propofol versus SAH-sevoflurane animals 2 hours after recovery and on postoperative day 1 (propofol versus sevoflurane: 14. 6 ± 3.4 vs 15. 9 ± 2.7 points, P = .034, and 16. 2 ± 3.5 vs 17. 8 ± 0.9 points, P = .015). Overall complete recovery from neurologic deficit was observed on day 7 in both SAH groups (18. 0 ± 0.0 vs 18. 0 ± 0.0 points, P = 1.000). Cortical vascular density increased to 80. 6 ± 15.0 vessels per field of view in SAH-propofol animals (vs 71. 4 ± 10.1 in SAH-sevoflurane, P < .001). Activation of glial cells, an indicator of neuroinflammation, was assessed by GFAP-positive astrocytes GFAP per field of view. Hippocampal GFAP-positive cells were 201 ± 68 vs 179 ± 84 cells per field of view in SAH-propofol versus SAH-sevoflurane animals (P < .001). CONCLUSIONS: Sevoflurane postconditioning improves survival by 23% (SAH-sevoflurane versus SAH-propofol). The sevoflurane intervention could attenuate the early neurologic deficit, while the long-term outcome was similar across the groups. A higher vascular density close to the SAH area in the propofol group was not associated with improved outcomes.

Bacteriophage predation promotes serovar diversification in Listeria monocytogenes.

Listeria monocytogenes is a bacterial pathogen classified into distinct serovars (SVs) based on somatic and flagellar antigens. To correlate phenotype with genetic variation, we analyzed the wall teichoic acid (WTA) glycosylation genes of SV 1/2, 3 and 7 strains, which differ in decoration of the ribitol-phosphate backbone with N-acetylglucosamine (GlcNAc) and/or rhamnose. Inactivation of lmo1080 or the dTDP-l-rhamnose biosynthesis genes rmlACBD (lmo1081-1084) resulted in loss of rhamnose, whereas disruption of lmo1079 led to GlcNAc deficiency. We found that all SV 3 and 7 strains actually originate from a SV 1/2 background, as a result of small mutations in WTA rhamnosylation and/or GlcNAcylation genes. Genetic complementation of different SV 3 and 7 isolates using intact alleles fully restored a characteristic SV 1/2 WTA carbohydrate pattern, including antisera reactions and phage adsorption. Intriguingly, phage-resistant L. monocytogenes EGDe (SV 1/2a) isolates featured the same glycosylation gene mutations and were serotyped as SV 3 or 7 respectively. Again, genetic complementation restored both carbohydrate antigens and phage susceptibility. Taken together, our data demonstrate that L. monocytogenes SV 3 and 7 originate from point mutations in glycosylation genes, and we show that phage predation represents a major driving force for serovar diversification and evolution of L. monocytogenes.

Hemodynamic Assessment of a Murine Heterotopic Biventricularly Loaded Cardiac Transplant in vivo Model.

BACKGROUND: Heterotopic heart transplantation (HHT) in rodent animal models represents an important technique enabling studies on organ transplantation immunology and pharmaceutical development. Recent investigations used nonworking HHT designs, with the left ventricle (LV) bypassed in the anastomosis system. In spite of their principal success, the lack of orthogonal ventricular filling leads to myocardial atrophy. However, when focusing on the cellular and molecular mechanisms involved in the in vivo remodeling of the myocardium or cell-based cardiovascular implants, a nonworking model is suboptimal as it lacks the native-analogous hemodynamic and metabolic situation. Here we present the hemodynamic and electrical assessment of a biventricularly loaded murine HHT method without the need for a combined heart-lung transplantation approach. METHODS: Heterotopic transplantations (n = 13) were performed on C57BL/6J-(H-2b) inbred mice (n = 13 donors, n = 13 recipients) by creating end-to-side anastomoses between the donors' cranial vena cava (CrVC) and the recipients' abdominal caudal vena cava (CVC), between the donors' ascending aorta and the recipients' abdominal aorta (aAo), and between the grafts' pulmonary trunk and the left atrium. After transplantation, a hemodynamic assessment using echocardiography (including 2D speckle tracking analysis) and electrocardiography was performed. RESULTS: The loaded HHT procedure in the mice was performed with an overall success rate of 61%. In 3 of the remaining 5 cases, only atrial function was restored. The median duration of the entire surgical procedure for the recipient animal was 190 (IQR 180-250) min. The mean heart rate in the loaded HHT group was 355 ± 6 bpm in comparison to the control group with an in situ heart rate of 418 ± 61 bpm. A native-like closing and opening pattern of the aortic and mitral valves (visible on both 2D and M-mode images) was observed, confirming a native-analogous loading of the LV. Pulsed-wave Doppler provided visualization of the flow across the region of anastomoses between the pulmonary trunk and the left atrium, reaching a mean maximum velocity of 382 ± 12 mm/s. Exemplary 2D speckle tracking analysis of the LV free wall and interventricular septum revealed some differences in vector directions in one animal when compared to the orthotopic native heart, indicating an asynchronous movement of the LV. CONCLUSIONS: These results demonstrate the technical (micro)surgical feasibility of a fully loaded HHT procedure in the murine model without using a combined heart-lung transplantation approach. The acute hemodynamic performance of the HHT grafts approximated the native orthotopic situation. This model may open up new options for the investigation of cellular and molecular questions in the murine cardiovascular in vivo system in the near future.

Does the type of anesthesia (regional vs. general) represent an independent predictor for in-hospital complications in operatively treated malleolar fractures? A retrospective analysis of 5262 patients.

PURPOSE: The impact of the type of anesthesia (regional vs. general anesthesia) on in-hospital complications in ankle fractures has not been thoroughly studied yet. Identifying factors that place patients at risk for complications following ankle fractures may help reduce their occurrence. The primary goal of this study was (1) to describe the cohort of patients and (2) to evaluate independent risk factors for complications during hospitalization. METHODS: We analyzed patients from 2005 to 2019 with an operatively treated isolated fracture of the medial or lateral malleolus using a prospective national quality measurement database. Patients were selected based on international classifications (ICD) and national procedural codes (CHOP). Uni- and multivariate analysis were applied. RESULTS: In total, we analyzed 5262 patients who suffered a fracture of the malleolus; 3003 patients (57%) had regional and 2259 (43%) general anesthesia. Patients with regional anesthesia were significantly older (51 vs. 46 years), but healthier (23 vs. 28% comorbidities) than patients who received general anesthesia. The in-hospital complication rate was not significantly lower in regional anesthesia (2.2% vs 3.0%). The type of anesthesia was not an independent predictor for complications while controlling for confounders. CONCLUSION: Type of anesthesia was not an independent predictor of complications; however, higher ASA class, age over 70 years, fracture of the medial versus lateral malleolus, longer preoperative stay, and duration of surgery were significant predictors of complications. Patient and procedure characteristics, as well as changes in medical care and epidemiological changes along with patient requests, influenced the choice of the type of anesthesia.