Currently no drugs are employed clinically to reverse the unconsciousness induced by general anesthetics. Our previous studies showed that caffeine, when given near the end of an anesthesia session, accelerated emergence from isoflurane anesthesia, likely caused by caffeine’s ability to elevate intracellular cAMP levels and to block adenosine receptors. These earlier studies showed that caffeine did not rouse either rats or humans from deep anesthesia (≥ 1 minimum alveolar concentration, MAC). In this current crossover study, we examined whether caffeine reversed the unconsciousness produced by light anesthesia (< 1 MAC) in the continued presence of isoflurane. The primary endpoint of this study was to measure isoflurane levels at the time of recovery of righting reflex, which was a proxy for consciousness. Rats were deeply anesthetized with 2% isoflurane (~1.5 MAC) for 20 minutes. Subsequently, isoflurane was reduced to 1.2% for 10 minutes, then by 0.2% every 10 min; animals were monitored until the recovery of righting reflex occurred, in the continued presence of isoflurane. Respiration rate, heart rate and electroencephalogram (EEG) were monitored. Our results show that caffeine-treated rats recovered their righting reflex at a significantly higher inspired isoflurane concentration, corresponding to light anesthesia, than the same rats treated with saline (control). Respiration rate and heart rate increased initially after caffeine injection but were then unchanged for the rest of the anesthesia session. Deep anesthesia is correlated with burst suppression in EEG recordings. Our data showed that caffeine transiently reduced the burst suppression time produced by deep anesthesia, suggesting that caffeine altered neuronal circuit function but not to a point where it caused arousal. In contrast, under light anesthesia, caffeine shifted the EEG power to high frequency beta and gamma bands. These data suggest that caffeine may represent a clinically viable drug to reverse the unconsciousness produced by light anesthesia.
Background: Although initial studies have demonstrated that concentrated bone marrow aspirate (cBMA) injections promote rotator cuff repair (RCR) healing, there are no randomized prospective studies investigating clinical efficacy. Hypothesis/Purpose: To compare outcomes after arthroscopic RCR (aRCR) with and without cBMA augmentation. It was hypothesized that cBMA augmentation would result in statistically significant improvements in clinical outcomes and rotator cuff structural integrity. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: Patients indicated for aRCR of isolated 1- to 3-cm supraspinatus tendon tears were randomized to receive adjunctive cBMA injection or sham incision. Bone marrow was aspirated from the iliac crest, concentrated using a commercially available system, and injected at the aRCR site after repair. Patients were assessed preoperatively and serially until 2 years postoperatively via the following functional indices: American Shoulder and Elbow Surgeons (ASES), Single Assessment Numeric Evaluation (SANE), Simple Shoulder Test, 12-Item Short Form Health Survey, and Veterans RAND 12-Item Health Survey. Magnetic resonance imaging (MRI) was performed at 1 year to assess rotator cuff structural integrity according to Sugaya classification. Treatment failure was defined as decreased 1- or 2-year ASES or SANE scores as compared with preoperative baseline, the need for revision RCR, or conversion to total shoulder arthroplasty. Results: An overall 91 patients were enrolled (control, n = 45; cBMA, n = 46): 82 (90%) completed 2-year clinical follow-up and 75 (82%) completed 1-year MRI. Functional indices significantly improved in both groups by 6 months and were sustained at 1 and 2 years (all P < .05). The control group showed significantly greater evidence of rotator cuff retear according to Sugaya classification on 1-year MRI (57% vs 18%; P < .001). Treatment failed for 7 patients in each group (control, 16%; cBMA, 15%). Conclusion: cBMA-augmented aRCR of isolated supraspinatus tendon tears may result in a structurally superior repair but largely fails to significantly improve treatment failure rates and patient-reported clinical outcomes when compared with aRCR alone. Additional study is warranted to investigate the long-term benefits of improved repair quality on clinical outcomes and repair failure rates. Registration: NCT02484950 (ClinicalTrials.gov identifier).
Background: Point-of-care treatment options for medium to large symptomatic articular cartilage defects are limited. Minced cartilage implantation is an encouraging single-stage option, providing fresh viable autologous tissue with minimal morbidity and cost. Purpose: To determine the histological properties of mechanically minced versus minimally manipulated articular cartilage. Study Design: Controlled laboratory study. Methods: Remnant articular cartilage was collected from fresh femoral condylar allografts. Cartilage samples were divided into 4 groups: cartilage explants with or without fibrin glue and mechanically minced cartilage with or without fibrin glue. Samples were cultured for 42 days. Chondrocyte viability was assessed using live/dead assay. Cellular migration and outgrowth were monitored using bright-field microscopy. Extracellular matrix deposition was assessed via histological staining. Proteoglycan content and synthesis were assessed using dimethylmethylene blue assay and radiolabeled 35S-sulfate, respectively. Type II collagen (COL2A1) gene expression was analyzed via polymerase chain reaction. Results: The mean viability of minced cartilage particles (34% ± 14%) was not significantly reduced compared with baseline (46% ± 13%) on day 0 ( P = .90). After culture, no significant difference in the percentage of live cells was appreciated between mechanically minced (58% ± 23%) and explant (73% ± 14%) cartilage in the presence of fibrin glue ( P = .52). The addition of fibrin glue did not significantly affect the viability of cartilage samples. The qualitative assessment revealed comparable cellular migration and outgrowth between groups. Proteoglycan synthesis was not significantly different between groups. Histological analysis findings were positive for COL2A1 in all groups, and matrix formation was appreciated in all groups. COL2A1 expression in minced cartilage (1.72 ± 1.88) was significantly higher than in explant cartilage (0.15 ± 0.07) in the presence of fibrin glue ( P = .01). Conclusion: Mechanically minced articular cartilage remained viable after 42 days of culture in vitro and was comparable with cartilage explants with regard to cellular migration, outgrowth, and extracellular matrix synthesis. Clinical Relevance: Mechanically minced articular cartilage is an encouraging intervention for the treatment of symptomatic cartilage defects. Further translational work is warranted to determine the viability of minced cartilage implantation as a single-stage therapeutic intervention in vivo.
The ability to return to sport (RTS) after articular cartilage injury is of vital importance to athletes. Discussing
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