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Study Objectives: To characterize public practices and perspectives on the use of consumer sleep technology (CST) and evaluate perspectives on using CST as a screening tool for obstructive sleep apnea (OSA)., Methods: We designed a survey instrument incorporating content from validated instruments (STOP-BANG and the Epworth Sleepiness Scale) and hypothesis-generated questions. Survey development involved multidisciplinary collaboration among three board-certified sleep medicine experts, researchers, and consumers. The survey was disseminated across a national sample of adults living in the United States via an online platform., Results: Among 897 respondents, the mean (SD) age was 47.5 (16.9) years; 73.1% were female, 81.8% were White, and 505 respondents (56.3%) reported having tracked sleep using CS. Factors associated with decreased odds of CST use included household income <$30,000 (OR 0.47, 95% CI 0.28-0.79; p=0.004), Medicaid insurance (OR 0.43, 95% CI 0.26-0.69; p=0.001), Medicare insurance (OR 0.59, 95% CI 0.41-0.84; p=0.004), and lack of a primary care physician (OR 0.55, 95% CI 0.33-0.91; p=0.021). Most respondents (91.1%) agreed or strongly agreed that screening for OSA would be a useful feature of CST, but respondents reporting an education of high school diploma or less (OR 0.48, 95% CI 0.29-0.79; p=0.004) were less likely to agree with this statement., Conclusions: Attitudes toward and use of CST differed based on demographic and socioeconomic factors. Further study is needed to understand and address barriers to CST adoption and to characterize implications for equitable access to care for sleep disorders., (© 2024 American Academy of Sleep Medicine.)

Objective: To evaluate the costs, time to surgery, and clinical outcomes associated with implementing a streamlined hypoglossal nerve stimulator (HGNS) implantation pathway., Study Design: Retrospective cohort study., Setting: Single tertiary care center in the United States from 2016 to 2023., Methods: Patients with a lack of complete concentric collapse of the velum during volitional snore on in-office laryngoscopy qualified for the streamlined HGNS pathway. This pathway consisted of confirmatory drug-induced sleep endoscopy (DISE) followed immediately by HGNS implantation during the same surgical encounter. Outcomes were compared to patients in the traditional pathway (standalone DISE followed by HGNS implantation on a later date)., Results: A total of 68 patients (13 streamlined, 55 traditional) with obstructive sleep apnea who underwent HGNS implantation were included. Patients were predominately male (70.6%) and White (95.6%) and had a mean (SD) age of 63.5 (10.0) years. The streamlined pathway was associated with a significant reduction in both hospital costs (mean difference $9258, 95% confidence interval [CI]: 3690-14,825; P  = .002) and time to surgery (mean decrease of 3.82 months, 95% CI: 0.83-6.80 months; P  = .013) compared to the traditional pathway. Patients in both groups had reduction in apnea-hypopnea index and Epworth Sleepiness Scale score, with no significant differences in comparisons between groups., Conclusion: In select patients, the streamlined HGNS pathway may expedite time to surgery and reduce hospital costs with comparable clinical outcomes to a traditional 2-stage pathway. Further research is warranted to validate patient selection and better understand longitudinal outcomes., Competing Interests: Dr Paul T. Hoff reports involvement on the Inspire Advisory Council, Cryosa safety monitor, and Nyxoah safety monitor. Dr Sonja G. Schütz reports grants or contracts between Huxley Medical Inc, Apple Inc, Oura Health Ltd, and the University of Michigan., (© 2024 The Author(s). OTO Open published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngology–Head and Neck Surgery Foundation.)

Purpose: Upper airway (UA) surgery is commonly employed in the treatment of patients with obstructive sleep apnea (OSA). The intricate pathophysiology of OSA, variability in sites and patterns of UA collapse, and the interaction between anatomical and non-anatomical factors in individual patients may contribute to possible surgical failures. This clinical consensus statement aims to identify areas of agreement among a development group comprising international experts in OSA surgery, regarding the appropriate definition, predictive factors in patients, and management of surgical failure in OSA treatment., Methods: A clinical consensus statement (CCS) was developed using the Delphi method by a panel of 35 contributors from various countries. A systematic literature review adhering to PRISMA guidelines was conducted. A survey consisting of 60 statements was then formulated and presented to the experts., Results: Following two rounds of the Delphi process, consensus or strong consensus was achieved on 36 items, while 24 items remained without consensus. Specifically, 5 out of 10 statements reached consensus regarding on the 'Definition of Surgical Success/Failure after OSA Surgery'. Regarding the 'Predictive Factors of Surgical Failure in OSA Surgery', consensus was reached on 10 out of 13 statements. In the context of the 'Diagnostic Workup in OSA Surgery', consensus was achieved on 9 out of 13 statements. Lastly, in 'Treatment in Surgical Failure Cases', consensus was reached on 12 out of 24 statements., Conclusion: The management of OSA after surgical failure presents a significant clinical challenge for sleep specialists. This CCS provides valuable guidance for defining, preventing, and addressing surgical failures in the treatment of OSA syndrome., (© 2024. The Author(s).)

Background: Evaluation and interpretation of the literature on obstructive sleep apnea (OSA) allows for consolidation and determination of the key factors important for clinical management of the adult OSA patient. Toward this goal, an international collaborative of multidisciplinary experts in sleep apnea evaluation and treatment have produced the International Consensus statement on Obstructive Sleep Apnea (ICS:OSA)., Methods: Using previously defined methodology, focal topics in OSA were assigned as literature review (LR), evidence-based review (EBR), or evidence-based review with recommendations (EBR-R) formats. Each topic incorporated the available and relevant evidence which was summarized and graded on study quality. Each topic and section underwent iterative review and the ICS:OSA was created and reviewed by all authors for consensus., Results: The ICS:OSA addresses OSA syndrome definitions, pathophysiology, epidemiology, risk factors for disease, screening methods, diagnostic testing types, multiple treatment modalities, and effects of OSA treatment on multiple OSA-associated comorbidities. Specific focus on outcomes with positive airway pressure (PAP) and surgical treatments were evaluated., Conclusion: This review of the literature consolidates the available knowledge and identifies the limitations of the current evidence on OSA. This effort aims to create a resource for OSA evidence-based practice and identify future research needs. Knowledge gaps and research opportunities include improving the metrics of OSA disease, determining the optimal OSA screening paradigms, developing strategies for PAP adherence and longitudinal care, enhancing selection of PAP alternatives and surgery, understanding health risk outcomes, and translating evidence into individualized approaches to therapy., (© 2022 ARS-AAOA, LLC.)

Hypoglossal nerve stimulation (HGNS) has emerged as a successful surgical treatment strategy for moderate to severe obstructive sleep apnea in patients failing first-line positive airway pressure therapy. HGNS explantation due to adverse events such as pain and infection is rare and has yet to be well described. Here, our correspondence describes the first case series of patients who have undergone explantation of the Inspire HGNS system. Five patients were identified who underwent HGNS explantation. Three patients underwent explantation due to magnetic resonance imaging (MRI) incompatibility. One patient underwent explantation due to poor cosmesis. One patient underwent explantation due to surgical site infection. Average operative explant time was 163 minutes. MRI incompatibility, poor cosmesis, and device-related infection are reasons for HGNS explantation. Future need for MRI or chest wall surgery should be considered in patients being evaluated for HGNS implants., (© The Authors 2022.)

Candidacy evaluation for hypoglossal nerve stimulation (HGNS) is resource intensive. This proof-of-concept study investigates use of in-office volitional snore during flexible laryngoscopy as an efficient, cost-effective screening tool for HGNS evaluation. Adults with moderate to severe obstructive sleep apnea that failed continuous positive airway pressure treatment (n = 41) underwent evaluation for HGNS from 2018 to 2019. Volitional snore and drug-induced sleep endoscopy (DISE) data were collected and scored by VOTE classification (velum/palate, oropharynx, tongue base, epiglottis). A chi-square test of independence was performed that demonstrated a significant relationship between volitional snore and DISE (χ 2 = 4.39, P = .036) for velum collapse pattern. Sensitivity and specificity of volitional snore for detecting velum collapse pattern were 93.6% (95% CI, 75.6%-99.2%) and 40% (95% CI, 12.2%-73.8%), respectively, illustrating its utility in screening for HGNS. Patients who demonstrate anterior-posterior velum collapse on volitional snore may be excellent candidates for confirmatory DISE at the time of HGNS implantation.

Introduced in 2010, transoral robotic surgery (TORS) is recognized as an effective treatment of moderate to severe obstructive sleep apnea (OSA) in the setting of lymphoid and muscular tongue base hypertrophy. Upper airway stimulation (UAS) or hypoglossal nerve stimulation has emerged as a promising treatment of patients with moderate to severe OSA who have failed continuous positive airway pressure. UAS has shown favorable success rates and low morbidity compared with traditional soft tissue and skeletal framework surgery. UAS is in its infancy as a surgical procedure and concerns exist regarding narrow candidacy criteria, postimplant device titration, and durability of treatment response., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Peritonsillar abscess (PTA) is a difficult diagnosis to make clinically, with clinical examination of even otolaryngologists showing poor sensitivity and specificity. Machine learning is a form of artificial intelligence that "learns" from data to make predictions. We developed a machine learning classifier to predict the diagnosis of PTA based on patient symptoms. We retrospectively collected clinical data and symptomatology from 916 patients who underwent attempted needle aspiration for PTA. Machine learning classifiers were trained on a subset of the data to predict the presence or absence of purulence on attempted aspiration. The performance of the model was evaluated on a holdout set. The accuracy of the top-performing algorithm, the artificial neural network, was 72.3%. Artificial neural networks can use patient symptoms to exceed human ability to predict PTA in patients with clinical suspicion for PTA. Similar models can assist medical decision making for clinicians who have suspicion of PTA.

Objective: Peritonsillar abscess (PTA) is a common infectious complication of pharyngeal infection managed by otolaryngologists and emergency room physicians. Streptococcus and Fusobacterium (e.g., Fusobacterium necrophorum, FN) species are commonly isolated pathogens. The aim of this study was to determine the implication of culture results on abscess recurrence following drainage., Methods: Single-institution retrospective review of patients treated at the University of Michigan between 2000 and 2017. Demographic and clinical outcome data were analyzed, including treatment details, culture data, and recurrence., Results: One hundred fifty-six of the 990 patients in our study developed recurrence of their abscess (16%). The age ranges most susceptible to recurrence included adolescent (22.9%) and young adult groups (17.1%). Recurrent patients were more likely to have experienced acute progression of symptoms (79% vs. 71%, P = 0.03), trismus (67% vs. 55%, P = 0.006), voice changes (65% vs. 57%, P = 0.04), and dysphagia (72% vs. 61%, P = 0.01) compared to nonrecurrent patients. They were also more likely to have clinical lymphadenopathy noted on initial examination (67% vs. 56%, P = 0.009). Culture data was sent for 852 patients (86%). The presence of FN was significantly more prevalent in the recurrent group (P < 0.0001)., Conclusion: There is a high observed prevalence of FN species within PTA aspirates in the recurrent PTA population. PTA aspirate should be sent for anaerobic growth to screen for Fusobacterium species. In addition, follow-up and lower threshold for subsequent tonsillectomy should be considered in this at-risk group., Level of Evidence: 3 Laryngoscope, 129:1567-1571, 2019., (© 2018 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives/hypothesis: An uncommon phenomenon in relation to the peritonsillar abscess (PTA) is the intratonsillar abscess (ITA) or formation of an abscess within tonsillar parenchyma. This study sought to characterize our experience with diagnosis and management of ITAs in the context of the PTA patient population., Study Design: Case-control series., Methods: This is a single-institution retrospective review of patients treated at the University of Michigan between 2000 and 2017., Results: Six hundred fifty-five adult patients were identified. The incidence of ITA within the PTA population was 7% (n = 43). Patients with ITA had lower mean white blood cell count (P = .03), lower proportion of trismus (P < .0001), otalgia (P = .007), vocal changes (P < .0001), and fewer incidences of acute progression of symptoms (P = .0007). On multivariable analysis, ITA patients were noted to be older, present with a longer duration of symptoms, and have greater incidence of neck pain and lymphadenopathy. Drainage was attempted in fewer ITA patients and was rarely successful (15%) in comparison to successful drainage for PTA patients (69%) (P < .0001)., Conclusions: Symptomatology differs for ITA, as fewer present with the classic PTA symptoms of otalgia, trismus, and voice alterations. The lack of classic symptoms likely leads to delayed presentation. A greater number of ITA patients presented with neck pain and lymphadenopathy. In the ITA population, aspiration attempts were more infrequent and less successful in yielding purulence. Given infrequent yield of pus and low overall recurrence rate, the diagnosing clinician should consider medical management in this distinct patient population., Level of Evidence: 4 Laryngoscope, 129:1354-1359, 2019., (© 2018 The American Laryngological, Rhinological and Otological Society, Inc.)

Objective: To determine the incidence of intratonsillar abscess (ITA) patients within the population of patients diagnosed with peritonsillar abscess (PTA) and to further characterize the differences in symptomatology and successful treatment strategies between the two groups., Methods: This study is a retrospective chart review of patients diagnosed with PTA or ITA at our institution from 2000 to 2017. Descriptive and inferential statistics are reported, including univariate and multivariate analyses., Results: A total of 335 pediatric (<18 years) patients presenting with a PTA or ITA were identified, 31 (9%) of whom were diagnosed with ITA. Patients with ITAs had significantly lower proportions of trismus, otalgia, and dysphagia and were less likely to experience acute progression from their initial symptoms. The ITA group had fewer attempted aspiration and drainage attempts, with those attempts significantly less successful than for the PTA group. Recurrence was uncommon in ITA patients in comparison to PTA patients., Conclusions: Intratonsillar abscess should be considered in the differential diagnosis for patients presenting with sore throat and concern for a pharyngeal infection or abscess. These patients have a significantly lower proportion of otalgia, trismus, vocal changes, and dysphagia. Given the low success rate of drainage attempts and lower recurrence rate, diagnosing physicians should consider medical management rather than procedural drainage in this patient population., (Copyright © 2018. Published by Elsevier B.V.)

Objectives/hypothesis: The aim of this study was to determine if drug-induced sleep endoscopy (DISE) was predictive of success for patients undergoing transoral robotic surgery (TORS) and multilevel procedures for sleep apnea., Study Design: Retrospective case series of patients who underwent TORS surgery for sleep apnea METHODS: Before and after polysomnograms were analyzed to assess improvement, success, and cure. Improvement was defined as any decrease in apnea-hypopnea index (AHI), success as an AHI <20 with a decrease >50%, and cure as an AHI <5. DISE videos were scored using the NOHL (nose, oropharynx, hypopharynx, larynx) and VOTE (velum, oropharynx, tongue, epiglottis) classification systems., Results: One hundred one patients were available for analysis. Eighty-seven percent of patients had an improvement in their AHI. Fifty-one percent met criteria for success, whereas 17% were cured. The degree of collapse at individual NOHL and VOTE subsites as well as total additive scores did not predict improvement, success, or cure. Patients with no oropharyngeal lateral collapse in the VOTE classification system were more likely to improve following surgery (P = .001); however, this effect did not hold for success or cure. Multivariate analysis of DISE variables was not predictive of success., Conclusions: In obstructive sleep apnea patients, there is a 51% success rate and a 17% cure rate. DISE, as scored by the NOHL and VOTE system, did not readily identify patients who would benefit most from surgery. Patients with lateral oropharyngeal collapse may be poorer candidates. Prospective, larger studies are required to further evaluate the use of DISE in predicting success following TORS., Level of Evidence: 4 Laryngoscope, 127:971-976, 2017., (© 2016 The American Laryngological, Rhinological and Otological Society, Inc.)

Obstructive sleep apnea-hypopnea syndrome (OSAHS) is a serious social health problem with significant implications on quality of life. Surgery for OSAHS has been criticized due to a lack of evidence to support its efficacy as well as the heterogeneous reporting of published outcomes. Moreover, the transoral robotic surgery (TORS) in the management of OSAHS is still in a relative infancy. Nevertheless, a review and meta-analysis of the published articles may be helpful. Among 195 articles, eight studies were included in the analysis. The mean of enrolled patients was 102.5 ± 107.9 (range 6-289) comprising a total of 820 cases. The mean age was 49 ± 3.27 and 285 patients underwent a previous sleep apnea surgery. The uvulopalatopharyngoplasty (UPPP) was the most common palatal procedure. The mean rate of failure was 34.4 % (29.5-46.2 %). Complications occurred in 21.3 % of the patients included in the analysis, most of them were classified as minor. Transient dysphagia represented the most common complication (7.2 %) followed by bleeding (4.2 %). TORS for the treatment of OSAHS appears to be a promising and safe procedure for selected patients seeking an alternative to continuous positive airway pressure (CPAP), although further researches are urgently needed.

Tracheostomy decannulation has always been considered a procedure with an attendant risk, especially in patients with a reduced upper airway diameter as is commonly observed in the obstructive sleep apnoea (OSA) population. We report on 4 cases where transoral robotic surgery (TORS) helped in the management of long-term cannulated patients. The aims of our paper are: 1. To demonstrate how the otolaryngology team can help identify patients at high risk for decannulation failure; and 2. To demonstrate how TORS may aid in the decannulation process of patients at high risk for failure due to severe tongue base hypertrophy. From our experience, TORS appears to offer an effective option to aid in the decannulation of patients with a severe hypertrophy of the base of tongue and floppy epiglottis., (© Copyright by Società Italiana di Otorinolaringologia e Chirurgia Cervico-Facciale, Rome, Italy.)

Pediatric obstructive sleep apnea syndrome (OSAS) is primarily caused by adenotonsillar hypertrophy. However, tongue base hypertrophy is increasingly being recognized as a cause, even after adenotonsillectomy. We report three cases of pediatric OSAS successfully treated by transoral robotic reduction of the tongue base. In all children, we were able to achieve improved retrolingual patency while avoiding significant procedure-related morbidity. In conclusion, tongue base reduction by transoral robotic surgery appears to be a feasible solution for the base of tongue obstruction due to lingual tonsil hypertrophy in pediatric patients.

Background/aims: To stratify outcomes in patients with moderate to severe obstructive sleep apnea-hypopnea syndrome (OSAHS) undergoing transoral robotic surgery (TORS) ± multilevel procedures according to Friedman stage., Methods: A total of 118 patients with moderate to severe OSAHS between 2010 and 2013 were stratified preoperatively by Friedman stage. All patients had TORS-assisted lingual tonsillectomy, either stand-alone or in combination with palatal surgery. Apnea-hypopnea index (AHI) was measured preoperatively and 3 months postoperatively. Success was defined as a decrease in AHI by 50% and AHI <20., Results: The average pre- and postoperative AHI was 43.0 and 22.6, respectively, and the overall success rate was 63%. When stratifying by Friedman stage, success was seen in 75% of stage I, 70% of stage II, 66% of stage III, and 10% of stage IV patients. When stratifying by preoperative BMI, success was seen in 75% of stage II and 72% of stage III patients with BMI <30, compared to 58% of stage II and 56% of stage III patients with BMI >30., Conclusions: TORS-assisted lingual tonsillectomy ± multilevel procedures can be successful in treating patients with moderate to severe OSAHS with Friedman stage I-III anatomy. Success rates are even greater if patients are stratified according to preoperative BMI, as those with BMI <30 are more likely to achieve success even with Friedman stage II-III anatomy., (© 2015 S. Karger AG, Basel.)

Background: Oral squamous cell cancer (OSCC) is often diagnosed in late stages. Informative biomarkers could play a key role in early diagnosis. Prior case-control studies identified discriminatory salivary mRNA markers for OSCC. The National Cancer Institute (NCI) recommends prospective-specimencollection, retrospective-blinded-evaluation (PRoBE) design study for rigorous biomarker identification and validation., Methods: A PRoBE design study enrolled 170 patients with lesions suspicious for OSCC. Saliva was collected before performing oral biopsy. Six pre-specified oral-cancer-associated mRNAs (IL1β, IL8, OAZ1, SAT, S100P, and DUSP1) and five housekeeping mRNAs (MT-ATP6, RPL30, RPL37A, RPL0, and RPS17) were measured by quantitative polymerase chain reaction (PCR) without knowledge of tissue diagnosis. A pre-specified multi-marker panel from prior NCI - Early Detection Research Network (EDRN) studies was evaluated in this new PRoBE dataset. Individual marker cycle thresholds (Ct) from PCR were also compared in cancer versus control, and new discriminatory models were generated., Results: The EDRN model was validated based on pre-specified statistical analysis plan. Ct values of individual mRNAs reflect an approximately twofold to nearly fourfold increase in concentration in invasive OSCC (P less than 0.01 for all). A new model from this intended-use population with incorporation of housekeeping genes demonstrates a maximal sum of sensitivity and specificity of 150.7% with an area under the receiver operating characteristic (ROC) curve of over 0.85., Conclusion: The validation of six pre-specified individual salivary transcriptome markers of OSCC and a pre-specified multi-marker model in a new prospective population supports the robustness of these markers and the multi-marker methodology. New models generated in this intended-use population have the potential to further enhance the decision process for early biopsy. Lesions at very low risk for cancer could be identified noninvasively as could those at significantly increased risk. Further study is necessary to assure effective implementation of this technology into routine clinical practice.

Objectives/hypothesis: To evaluate the safety and feasibility of the da Vinci Surgical System in transoral robotic-assisted surgery for benign indications., Study Design: A multicenter, single-arm, retrospective case series., Methods: Perioperative outcomes were recorded for patients presenting with obstructive sleep apnea, airway obstruction, lingual tonsillar/tonsillar/tongue base hypertrophy, or dysphagia who underwent one or more transoral procedures, including lingual tonsillectomy and tongue base resection (partial glossectomy) at one of three US institutions., Results: Between January 2010 and October 2013, 285 patients (age 51.5 years, body mass index 30.5 kg/m(2) ) underwent 293 procedures. No conversions or blood transfusions were needed. The average operative time was 86.7 minutes, and the average volume of tissue resected (lingual tonsil and tongue base) was 8.3 mL. Hospital stays averaged 1.8 days, and the postoperative complication rate was 20.7%. There were no complications specifically related to the use the da Vinci Surgical System, and none of the complications were life threatening., Conclusions: These results demonstrate that it is safe and feasible to use the da Vinci Surgical System to perform lingual tonsillectomy and base of tongue resection (partial glossectomy) procedures for benign indications., Level of Evidence: 4, (© 2014 The American Laryngological, Rhinological and Otological Society, Inc.)

Importance: Patients who undergo surgery for obstructive sleep apnea (OSA) have acceptable perioperative morbidity that is similar to that seen in other sleep-related surgical procedures., Objective: To perform the first large-scale evaluation of perioperative management and postoperative complications in patients who undergo transoral robotic surgery (TORS) for OSA., Design, Setting, and Participants: Retrospective cohort study from 2010 to 2013 of 166 adult patients with moderate to severe OSA (defined as apnea-hypopnea index, >20) who had experienced failure of conventional therapy with positive airway pressure and underwent TORS at an academic practice with follow-up greater than 3 months., Interventions: Transoral robotic surgery with or without additional multilevel airway procedures., Main Outcomes and Measures: Major and minor complication rates., Results: There were 122 men and 44 women with a mean (SD) age of 54.6 (12.3) years. The mean (SD) American Society of Anesthesiologists (ASA) score was 2.3 (0.5). There were 11 major complications, including secondary bleeding requiring intervention (7 patients), pulmonary embolism requiring anticoagulation therapy (2 patients), aspiration requiring prolonged hospitalization (1 patient), and dysphagia resulting in gastrostomy tube dependence (1 patient). There were 32 minor complications, including dehydration and/or uncontrolled pain (16 patients), globus sensation (8 patients), bleeding (5 patients), lip burn (2 patients), and pharyngeal laceration during intubation (1 patient); the majority resolved without sequelae. Preoperative ASA score (P = .003) and number of procedures performed (P = .004) predicted a postoperative complication. Age (P = .29), body mass index (P = .55), apnea-hypopnea index (P = .67), lowest arterial oxygen saturation (P = .63), number of comorbidities (P = .46), and individual comorbidities did not predict a complication., Conclusions and Relevance: Transoral robotic surgery can be safely performed in patients with OSA with an acceptable complication rate. Complications are similar to those seen with other surgical treatments of OSA and were only predicted by ASA score and number of procedures performed.

Objective: To determine the predictors of success in patients undergoing transoral robotic surgery (TORS) and multilevel procedures for the management of moderate-to-severe obstructive sleep apnea hypopnea syndrome (OSAHS)., Methods: A total of 121 patients (83 male, 38 female) underwent TORS between 2010 and 2013. All patients had robotic assisted lingual tonsillectomy, either as stand-alone surgery or in combination with palatal Z-plasty, lateral pharyngoplasty or uvulopalatopharyngoplasty. The apnea-hypopnea index (AHI) and body mass index (BMI) were measured preoperatively and 3 months postoperatively. Success was defined as AHI <20 and a decrease in AHI by 50%., Results: There was a significant difference in the preoperative and postoperative AHI in the entire cohort (42.7 vs. 22.2; p < 0.001). Overall, 84.3% of patients had an improvement in their AHI, 51.2% of patients met the criteria for success, and 14% met the criteria for cure defined as AHI <5. When stratifying by BMI, there was a significant difference in success when comparing patients with a BMI <30 versus those with a BMI >30 (69.4 vs. 41.7%; p = 0.004). The cure rate was 15.3% in patients with a BMI <30 and 11.1% in those with a BMI >30 (p = 0.54)., Conclusions: TORS lingual tonsillectomy and multilevel procedures were successful in treating moderate-to-severe OSAHS in selected patients. Preoperative BMI helps the clinician to predict success in these patients, with two thirds of patients having a clinically useful benefit., (© 2014 S. Karger AG, Basel.)

Background: The aim of this study was to create benchmarks for evaluating clinical outcomes and complications of transoral robotic surgeries (TORS) in a multicenter setting., Methods: 243 TORS for obstructive sleep apnea/hypopnea syndrome (OSAHS) operations, carried out between 2008 and 2012, were analyzed at 7 different centers. The average hospitalization was 3.5 days. The mean patient age was 50 ± 12 years, the average BMI at the time of the procedure was 28.53 ± 3.87 and the majority of the patients were men (81%)., Results: The mean preoperative and postoperative apnea/hypopnea index was 43.0 ± 22.6 and 17.9 ± 18.4, respectively (p < 0.001). The mean preoperative and postoperative Epworth Sleepiness Scale score was 12.34 ± 5.19 and 5.7 ± 3.49, respectively (p < 0.001). The mean pre- and postoperative lowest O2 saturation was 79.5 ± 8.77 and 83.9 ± 6.38%, respectively (p < 0.001)., Conclusions: Patients undergoing TORS as part of a multilevel approach for the treatment of OSAHS have a reasonable expectation of success with minimal long-term morbidity., (© 2014 S. Karger AG, Basel.)

In the present study the impact of environmental metal contamination in gibel carp (Carassius auratus gibelio) was investigated coupling disturbances in subcellular metal distribution to effect biomarkers. Gibel carp were caught at six different sampling sites in Flanders (Belgium), characterized by different degrees in environmental metal contamination. Tissue Cd, Cu and Zn concentrations and total metallothioneon (MT) levels were determined in gills, liver and kidney. Cytosolic metal distribution was measured in the main accumulating organs, liver and kidney, revealing tissue- and metal-dependent profiles. The MT pool dominated the cytosolic distribution profile. Although the importance of the MT pool increased with increasing environmental and cytosolic metal concentrations, also an undefined fraction of Cu and Cd fractions (probably free metal ions or metals bound to small organic complexes) increased at the most contaminated sampling sites. Disturbances in serum ion concentrations, serum alanine aminotransferase activity (ALT), hematocrite and condition factor were measured, as indicators of toxic effects. At the sampling site with the highest environmental Cd pollution a significant decrease in serum Ca(2+) concentrations and a significantly increased serum ALT activity were measured suggesting incomplete detoxification of Cd. Increased serum ALT concentrations suggested structural liver damage. The fact that the liver tissue, and probably also the kidney, could not cope with this high Cd burden in combination with the increased uptake of dissolved Cd through the gills most probably contributed to the perturbed serum Ca(2+) homeostasis., ((c) 2009 Elsevier Inc. All rights reserved.)

Objective: To evaluate the practice of otolaryngologists treating reflux-induced upper-respiratory disease in a nationwide survey., Study Design: Survey study using an anonymous questionnaire containing clinical vignettes., Subjects and Methods: The survey was mailed to all 6,899 board-certified fellow members in practice in the American Academy of Otolaryngology-Head and Neck Surgery residing in the United States., Results: One thousand seven hundred twenty questionnaires were returned. Respondents empirically treated reflux-induced upper-respiratory disease with proton pump inhibitors once daily and twice daily 63% and 31%, respectively. Fifteen percent did not instruct their patients on how to take the proton pump inhibitors. Of those who instructed their patients, 22% advised dosing before breakfast, 32% before breakfast and again before dinner, and 46% recommended other timings. When prescribing twice-per-day dosing, 64% responded to give before breakfast and dinner and 28% responded before breakfast and at bedtime., Conclusion: Suboptimal dosing of proton pump inhibitors is prevalent among otolaryngologists treating reflux-induced upper-respiratory disease.

A perfluorooctane sulfonic acid (PFOS) biomonitoring survey was conducted on great tit (Parus major) and blue tit (Parus caeruleus) nestlings from Blokkersdijk, a bird reserve in the proximity of a fluorochemical plant in Antwerp (Belgium) and Fort IV, a control area. PFOS, together with 11 organochlorine pesticides, 20 polychlorinated biphenyl congeners and 7 polybrominated diphenyl ethers were measured in liver tissue. The hepatic PFOS concentrations at Blokkersdijk (86-2788 and 317-3322 ng/g wet weight (ww) for great and blue tit, respectively) were among the highest ever measured and were significantly higher than at the control area (17-206 and 69-514 ng/g ww for great and blue tit, respectively). The hepatic PFOS concentration was species- and sex-independent and correlated significantly and positively with the serum alanine aminotransferase activity and negatively with the serum cholesterol and triglyceride levels in both species but did not correlate with condition or serum protein concentration. In the great tit, a significant positive correlation was observed between the liver PFOS concentration and the relative liver weight. In the blue tit, the hepatic PFOS concentration correlated positively and significantly with hematocrite values. None of the investigated organohalogen pollutants except for PFOS were suggested to be involved in the observed biological alterations.

A perfluorooctane sulfonic acid (PFOS) assessment was conducted on gibel carp (Carassius auratus gibelio), carp (Cyprinus carpio), and eel (Anguilla anguilla) in Flanders (Belgium). The liver PFOS concentrations in fish from the Ieperlee canal (Boezinge, 250-9031 ng/g wet weight, respectively) and the Blokkersdijk pond (Antwerp, 633-1822 ng/g wet weight) were higher than at the Zuun basin (Sint-Pieters-Leeuw, 11.2-162 ng/g wet weight) and among the highest in feral fish worldwide. Eel from the Oude Maas pond (Dilsen-Stokkem) and Watersportbaan basin (Ghent) had PFOS concentrations ranging between 212 and 857 ng/g wet weight. The hepatic PFOS concentration was significantly and positively related with the serum alanine aminotransferase activity, and negatively with the serum protein content in eel and carp. The hepatic PFOS concentration in carp correlated significantly and negatively with the serum electrolyte concentrations whereas a significant positive relation was found with the hematocrit in eel. Although 13 organochlorine pesticides, 22 polychlorinated biphenyl (PCB) congeners and 7 polybrominated diphenyl ethers (PBDEs) were also measured in the liver tissue, only PCB 28, PCB 74, gamma-hexachlorocyclohexane (gamma-HCH) and hexachlorobenzene (HCB) were suggested to contribute to the observed serological alterations in eel.

Wood mice (Apodemus sylvaticus) were captured at Blokkersdijk, a nature reserve in the immediate vicinity of a fluorochemical plant in Antwerp, Belgium, and at Galgenweel, 3 kilometers farther away. The liver perfluorooctane sulfonic acid (PFOS) concentrations in the Blokkersdijk mice were extremely high (0.47-178.55 micro g/g wet weight). Perfluorononanoic, perfluorodecanoic, perfluoroundecanoic, and perfluorododecanoic acids were found sporadically in the liver tissue of the Blokkersdijk mice. The liver PFOS concentrations at Galgenweel were significantly lower than those at Blokkersdijk (0.14-1.11 micro g/g wet weight). Further results suggest sex independence of the liver PFOS levels, increased levels of PFOS bioaccumulation in older mice, and maternal PFOS transfer to the young. Several liver end points were significantly elevated in the Blokkersdijk mice: liver weight, relative liver weight, peroxisomal beta-oxidation activity, microsomal lipid peroxidation level, and mitochondrial fraction protein content. For the mitochondrial fraction catalase activity, no significant difference between locations was found. The liver weight, relative liver weight, and liver microsomal lipid peroxidation level increased significantly with the liver PFOS concentration. No indications for PFOS-mediated effects on the serum triglyceride, cholesterol, or potassium levels were obtained. The liver PFOS concentration was negatively related to the serum alanine aminotransferase activity.

This is the first study to report on concentrations of perfluorinated organochemicals (FOCs) in marine mammals stranded along the southern North Sea coast in relation to stable nitrogen and carbon isotope ratios (delta15N and delta13C). The presence of FOCs in top predators such as marine mammals would indicate a potential biomagnification of these compounds and their widespread occurrence. Liver and kidney tissues of nine marine mammal species have been sampled. Among all the measured FOCs compounds, PFOS (perfluorooctane sulfonate) was predominant in terms of concentration. The highest PFOS concentrations were found in the liver of harbor seal compared to white-beaked dolphin, harbor porpoise, gray seal, sperm whale, white-sided dolphin, striped dolphin, fin whale, and hooded seal. PFOS concentrations differed significantly between sexes and age classes in harbor porpoises. Stable isotope measurements (delta13C and delta15N) were used in this study to describe the behavior of contaminants in food webs. We found a significant (p < 0.05) linear relationship between PFOS concentrations in livers of harbor porpoises and both muscle delta13C and delta15N measurements. Harbor and gray seals and white-beaked dolphin, which displayed the highest trophic position, contained the highest PFOS levels, while offshore feeders such as sperm whales, fin whales, striped dolphin, and white-sided dolphin showed lower PFOS concentrations than inshore species.

Over the past decades little research has been conducted on the environmental behavior and effects of fluorinated organochemicals (FOCs). Recently it has been reported that perfluorooctane sulfonic acid (PFOS) is occurring worldwide. Little is known about the PFOS levels in organisms originating from the southern North Sea and the Western Scheldt estuary. In this study, we determined, for the first time, the PFOS-exposure levels in Crangon crangon, Carcinus maenas, and Asterias rubens from these ecosystems. Concentrations on a wet-weight basis in soft tissues of shrimp, crab, and starfish ranged from 19 to 520 ng/g, from 24 to 877 ng/g, and from 9 to 176 ng/g, respectively. These results show the existence of a PFOS pollution gradient in organisms along the Western Scheldt estuary, with the highest concentrations near Antwerp. The range of PFOS levels in shrimp and crab are slightly higher in coastal regions compared with sampling sites in open water. This study shows widespread distribution of PFOS in the Belgian and Dutch marine and estuarine environment at rather high concentrations.

A biomonitoring campaign was conducted in the Belgian North Sea and in the Western Scheldt (The Netherlands) with the primary goal to assess perfluorooctane sulfonic acid (PFOS) contamination and distribution in different biota. This study covers the results obtained for bib (Trisopterus luscus) and plaice (Pleuronectes platessa) and includes the assessment of some stress-related biochemical endpoints. Analysis of liver and muscle PFOS concentrations of both species provided evidence for the existence of a PFOS pollution gradient along the Western Scheldt with higher levels at the upstream locations and a lower degree of PFOS pollution at the marine locations. Cellular necrosis was studied by measuring aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels in the serum. Serum ALT but not serum AST was shown to correlate positively with the PFOS liver concentration in bib (r = 0.44, p < 0.05), indicating that PFOS might contribute to the induction of hepatic damage in bib in the area of study. Analysis of total carbohydrate, lipid, and protein content of bib liver tissue revealed a positive correlation between the protein content and the PFOS liver concentration (r = 0.55, p < 0.01). Whether this is due to induction of compensatory mechanisms, detoxification, or repair processes remains unclear.

In the present study we evaluated the toxicological effects of a scarcely documented environmental pollutant, perfluorooctane sulfonic acid (PFOS), on selected biochemical endpoints in the common carp, Cyprinus carpio. Juvenile organisms were exposed to PFOS through a single intraperitoneal injection (liver concentrations ranging from 16 to 864 ng/g after 5 days of exposure) and after 1 and 5 days effects were assessed in liver and serum of the exposed organisms. The investigation of the hepatotoxicity of PFOS included the determination of the peroxisome proliferating potential (peroxisomal palmitoyl CoA oxidase and catalase activity) and the compounds influence on the average DNA basepair length (ABPL) by agarose gel electrophoresis. Total antioxidant activity (TAA), cholesterol and triglyceride levels were monitored in the serum. After 1 day of exposure the ABPL was significantly increased in the 270 and 864 ng/g treatment groups. After 5 days of exposure significant increases relative to the control were observed for the 16, 270 and 864 ng/g treatment groups. Enzyme leakage from the liver was investigated by measurement of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities in the serum. At 561, 670 and 864 ng/g PFOS a significant increase in serum ALT activity became apparent after 5 days of exposure with values ranging from 159 to 407% relative to the control. For serum AST activity a significant increase for the 864 ng/g treatment group was observed with a value of 112% relative to the control. Determination of the polymorphonuclear leukocyte migration into liver tissue as assessed through myeloperoxidase (MPO) activity in liver, was used as an indicator for inflammation. It appeared that inflammation was not involved in the observed membranous enzyme leakage for the 561, 670 and 864 ng/g PFOS treatment groups. The results of this study suggest that PFOS induces inflammation-independent enzyme leakage through liver cell membranes that might be related to cell necrosis. Furthermore, results show that PFOS does not significantly affects serum antioxidant levels nor does it clearly induce peroxisome proliferation in carp. This study also points out that PFOS might interfere with homeostasis of the DNA metabolism. The results of these biochemical analyses were used to perform an initial hazard assessment study indicating that PFOS levels observed in tissues of wildlife populations could induce a clear rise in serum transaminase levels indicative for disruption of hepatocyte membrane integrity.

Reconstruction of extensive laryngotracheal stenosis continues to pose a significant surgical challenge. Previous work in our laboratory has demonstrated the utility of vascularized perichondrium for reconstruction of cervical tracheal defects in a rabbit model. Because most potential vascularized donor sites in human beings are periosteal, it was important to demonstrate that vascularized periosteum was also useful for laryngotracheal reconstruction in a larger animal model. We therefore performed a 2-stage reconstruction of a circumferential, segmental cervical tracheal defect using a revascularized, tubed myoperiosteal graft in a canine model (n = 8). A rigid, patent tube was produced in 6 animals (75%) after completion of the first stage (7 to 10 weeks). After transfer of the vascularized free graft to the tracheal defect, 5 of 6 animals survived from 4 to 18 weeks. Severe stenosis (>90%) was present in 2 animals, and moderate stenosis (40% to 60%) was present in the remaining 3 animals. One animal was observed for 18 weeks and was found to have a 40% circumferential stenosis at autopsy. Light microscopy revealed exuberant bone proliferation in all specimens. Unrestrained osteogenesis may limit the utility of vascularized periosteum in reconstruction of extensive tracheal defects.

This study addresses the potential for ongoing cartilage proliferation after repair of laryngotracheal stenosis with vascularized perichondrium. We randomly assigned 32 New Zealand white rabbits to 1 of 3 groups: group 1 (early cartilage growth, n = 10), group 2 (long-term cartilage growth after pedicle ligation, n = 11), and group 3 (long-term cartilage growth without pedicle ligation, n = 11). Bilateral auricular perichondrocutaneous flaps were elevated and transposed into full-thickness anterior tracheal wall or anterior cricothyroid membrane defects. Six weeks after elevation of the flap, animals were randomly assigned to undergo ligation of either the right or left vascular pedicle (group 2), with the contralateral auricular flap used as a matched control (group 3). Neochondrogenesis was present at 6 weeks in group 1 (0.74 +/- 0.14 mm, n = 12 ears). Cartilage thickness did not differ between groups 2 and 3 one year after ligation of the vascular pedicle: group 2 (0.48 +/- 0.24 mm, n = 18) versus group 3 (0.42 +/- 0.12 mm); P > 0.05. We conclude that in the rabbit model, chondrogenesis did not appear to be ongoing and did not result in late stenosis of the reconstructed airway. Furthermore, delayed ligation of the vascular pedicle neither inhibited nor stimulated cartilage proliferation.

This study was performed to assess the effect of BMY21190, an inhibitor of cAMP phosphodiesterase, on infarct size using a canine ischemic model that underwent a 90-min occlusion and a 6-hour reperfusion of the left coronary artery. The infarct zone/area at risk of the BMY21190 group was significantly smaller than that of the vehicle group (36.1 +/- 7.8%; 62.4 +/- 4.3%, respectively; p < 0.05). Myeloperoxidase activity, an indicator of neutrophil infiltration, was significantly correlated to infarct size (r = 0.6893, p < 0.02). Myeloperoxidase activity (0.14 +/- 0.07 U/100 mg tissues) measured in the area at risk from hearts of the BMY21190-treated group was significantly lower than that of the vehicle-treated tissue (0.40 +/- 0.08 U/100 mg tissue, p < 0.05). It is suggested that BMY21190 reduces infarct size through the inhibition of neutrophil infiltration in the canine model.

Objectives: The purpose of this study was to assess the anti-thrombotic potential of various forms of aspirin administration., Background: Platelet activation in response to endothelial injury has been implicated in acute coronary syndromes., Methods: Delivering 100-microA anodal direct current to the intima of the left circumflex coronary artery in dogs at a site of moderate external stenosis provides a thrombogenic model of vascular injury. Animals were treated with aspirin (Group I, 20 mg/kg intravenously [n = 11]; Group II, 4.6 mg/kg intravenously [n = 6]; Group III, 4.6 mg/kg orally 18 h before the experiment [n = 7]) or vehicle (Group IV, control [n = 11])., Results: The time required for thrombotic occlusion to occur was longer and the incidence of thrombosis was lower in Group I (Group I, 238 +/- 7 min [n = 2]; Group II, 127 +/- 25 min [n = 3]; Group III, 156 +/- 35 min [n = 6]; Group IV, 90 +/- 11 min [n = 11]) (p < 0.05). Thrombus mass was smaller in Group I (Group I, 5.0 +/- 0.8 mg; Group II, 12.2 +/- 2.6 mg; Group III, 11.6 +/- 3.9 mg; Group IV, 9.1 +/- 1.6 mg) (p < 0.05). Initial hemodynamic variables did not differ among groups. An increase in mean arterial pressure was noted for several hours after intravenous aspirin administration in Group I (99 +/- 5 to 110 +/- 4 mm Hg) (p < 0.05). Left circumflex coronary artery blood flow was stable for 5 h in Group I (Group I, 31 +/- 2 to 26 +/- 4 ml/min) but decreased in all the other groups (Group II, 26 +/- 4 to 10 +/- 5 ml/min; Group III, 27 +/- 5 to 7 +/- 7 ml/min; Group IV, 29 +/- 4 to 0 ml/min) (p < or = 0.05). The in vivo area of left ventricle perfused by the left circumflex coronary artery was not different among groups. Platelet counts were similar and did not change over the course of the protocol. Ex vivo arachidonic acid-induced platelet aggregation decreased in all groups after aspirin (p < or = 0.001). Indium-111-labeled platelet adherence to the coronary vasculature was decreased in distal vessel segments after all doses of aspirin (p < 0.05). Platelet deposition in thrombi was similar for all treatment groups., Conclusions: High dose intravenous aspirin has salutary effects. It stabilizes left circumflex coronary artery blood flow, prolongs the time to thrombosis, reduces the incidence of thrombotic occlusion, reduces thrombus mass and limits platelet adherence to sites of arterial injury. Low dose aspirin given intravenously or orally was ineffective. When persistent intracoronary thrombi precipitate unstable coronary syndromes, high dose intravenous aspirin may be useful in the acute period even though platelets continue to interact with injured vascular segments through aspirin-insensitive mechanisms.

The protective effect of amlodipine was studied in isolated blood-perfused cat hearts made globally ischemic for 60 min followed by reperfusion for 60 min. Ischemia-induced alterations of left ventricular developed pressure and compliance were monitored. Amlodipine produced significant decreases in myocardial oxygen consumption (6.2 +/- 0.4 to 4.4 +/- 0.4 ml of oxygen/min/100 g) and coronary vascular resistance, as assessed by changes in perfusion pressure (120 +/- 1 to 100 +/- 4 mm Hg). When administered before the onset of global ischemia, amlodipine decreased the development of ischemic contracture as reflected by a progressive increase in resting left ventricular diastolic pressure. The return of contractile function, 60 min after reperfusion, was improved significantly in amlodipine-treated hearts compared to controls and there was better maintenance of the tissue concentration of Na+, Ca2+, and K+. In a canine model of regional myocardial ischemia (6 h) followed by reperfusion, amlodipine at 150 microg/kg, administered 15 min before reperfusion (90 min), reduced infarct size expressed as a percentage of the area at risk (34.5 +/- 3.8% vs. 45.9 +/- 2.8%, p = 0.027). We conclude that amlodipine reduces myocardial ischemic injury by mechanism(s) that may involve a reduction in myocardial oxygen demand as well as by positively influencing transmembrane Ca2+ fluxes during ischemia and reperfusion.

The cardioprotective effect of amlodipine, a long-acting dihydropyridine derivative, was studied in 2 experimental models of ischemia and reperfusion. Isolated and blood-perfused feline hearts were made globally ischemic for 60 minutes and then reperfused for 60 minutes. Alterations of left ventricular developed pressure and compliance were monitored in both amlodipine-treated hearts and saline-treated control animals. Changes in perfusion pressure indicated that amlodipine significantly reduced myocardial oxygen consumption and coronary vascular resistance. Furthermore, a progressive increase in resting left ventricular diastolic pressure indicated that amlodipine, administered before the onset of global ischemia, attenuated the development of ischemic contracture. Return of contractile function 60 minutes after reperfusion and maintenance of tissue concentrations of electrolytes were significantly better in the amlodipine-treated group than in the control animals. In intact canine hearts, regional myocardial ischemia was induced for 90 minutes, followed by 6 hours of reperfusion. Although the hemodynamic variables and the size of the region of risk did not differ significantly between treated animals and control animals, the infarct size was significantly smaller in the amlodipine-treated group than in the control animals, and a gradual reduction in coronary blood flow was observed in the control group that was prevented in the amlodipine group. A comparison of these findings with those observed with oxygen radical scavengers also is discussed. A detailed report of these studies was published in The American Journal of Cardiology (1989;64:101I-116I). This review is included here to maintain continuity of the symposium for the convenience of the reader.

The endogenous compound adenosine may play a role in limiting myocardial ischemia-reperfusion injury through its ability to cause vasodilation, modulate cardiac adrenergic responses, inhibit neutrophil function, or modulate energy supply and demand of the myocardium. The local anesthetic lidocaine has been shown to be protective against myocardial ischemia-reperfusion injury, although its mechanism of action remains unresolved. We hypothesized that administration of exogenous adenosine during reperfusion would limit the size of the infarct that results from a period of ischemia and reperfusion only when the animals are treated with lidocaine. Male, mongrel dogs (13.0-20.0 kg) were anesthetized (30 mg/kg i.v. sodium pentobarbital), and a left thoracotomy was performed. The left circumflex coronary artery (LCx) was isolated and instrumented with an electromagnetic flow probe, a 25-gauge nonobstructing intracoronary catheter, and a critical stenosis. The dogs were allocated randomly to one of four groups: 1) control, n = 13, (saline), 2) adenosine, n = 13, (0.15 mg/kg/ml/min i.c. for the first hour of reperfusion), 3) lidocaine, n = 9, (2.0 mg/kg i.v. given immediately before coronary artery occlusion and just before reperfusion), or 4) adenosine plus lidocaine, n = 11. The LCx was occluded for 90 minutes and reperfused for 6 hours. Regional myocardial blood flow (RMBF) was determined (n = 6 per group) at 80 minutes of occlusion and at 45 minutes of reperfusion with radiolabeled microspheres. RMBF determinations revealed an increase in blood flow to the inner two thirds of the myocardium at 45 minutes of reperfusion only in the presence of the combined treatment. Adenosine treatment alone or lidocaine treatment alone did not affect RMBF. Quantification of infarct size (triphenyltetrazolium method) expressed as a percent of the area at risk revealed a significant limitation of infarct size only in the group treated with both adenosine and lidocaine: control, 47.8 +/- 6.6%; adenosine, 45.0 +/- 3.2%; lidocaine, 46.9 +/- 6.0%; and adenosine and lidocaine, 20.8 +/- 5.6%. Statistical analyses were performed with two-way analysis of variance to account for the two individual drug treatments. The findings show that intracoronary administration of exogenous adenosine, at the dose used, is only effective at limiting myocardial infarct size when administered to lidocaine-treated animals.

Available data demonstrate that oxygen free radicals and derived reactive species of oxygen are produced during myocardial ischemia as well as upon reperfusion of the ischemic tissue. The present study was designed to determine if polyethylene glycol-conjugated superoxide dismutase (PEG-SOD), with its extended plasma half-life in excess of 30 hours in contrast to the native form of the enzyme (Native-SOD), could provide protection to the ischemic myocardium subjected to a 6-hour regional ischemia followed by reperfusion for 24 hours. We hypothesized that myocardial injury due to an ischemic interval is a dynamic process involving the sustained production of cytotoxic oxygen radicals that may continue beyond the ischemic interval. The ability to demonstrate a protective effect of the free radical scavenger enzyme superoxide dismutase would require the continued presence of the antioxidant during the ischemic interval and especially during reperfusion. To test this hypothesis, 22 anesthetized, open-chest dogs underwent 6 hours of circumflex coronary artery occlusion followed by reperfusion for 24 hours. Rapid administration of either Native-SOD (1,000 U/kg), PEG-SOD (1,000 U/kg), PEG-albumin (PEG-ALB), or 0.9% sodium chloride solution for injection (saline) was administered via the left atrium 15 minutes before occlusion of the vessel. A continuous infusion of an additional 1,000 U/kg of the respective enzyme interventions or an equivalent volume of PEG-ALB or saline was given during the 6-hour coronary artery occlusion and terminated 15 minutes after reperfusion. The animals were euthanized 24 hours after reperfusion, and the myocardial region at risk and the infarct region were quantitated by the tetrazolium method. The area of myocardium at risk of infarction, expressed as a percent of the left ventricle, did not differ among the groups: Native-SOD (n = 8), 46.2 +/- 1.8%; PEG-SOD (n = 6), 45.7 +/- 2.1%; PEG-ALB, 38.4 +/- 2.3% (n = 4); and saline 46.0 +/- 2.1% (n = 4). Hemodynamic parameters, the calculated rate-pressure-product, as well as regional myocardial blood flow (radiolabeled microsphere method) in the endocardial, midmyocardial, and epicardial segments of the risk and the nonrisk regions were comparable for all groups. Mean infarct size, determined 24 hours after reperfusion, in the group treated with PEG-SOD was 47.1 +/- 2.9% of the area at risk (n = 6), significantly smaller than that observed in each of the other treatment groups: Native-SOD, 63.5 +/- 2.2% (n = 8); PEG-ALB, 64.6 +/- 2.4% (n = 4); saline, 70.8 +/- 2.2% (n = 4).(ABSTRACT TRUNCATED AT 400 WORDS)

Disagreement regarding the cardioprotective role of superoxide dismutase may relate to the use of different durations for induction of ischemic injury and reperfusion. The present study employed superoxide dismutase conjugated to polyethylene glycol (PEG-SOD), which has a half-life greater than 30 hours. Two protocols differing in the mode of administration and the duration of the reperfusion interval were used. Dogs were subjected to occlusion of the circumflex coronary artery for 90 minutes, then reperfused for 6 hours (Protocol A) or 4 days (Protocol B). The dogs received either polyethylene glycol conjugated to albumin (PEG-ALB) or PEG-SOD (1,000 U/kg). In Protocol A, treatment was administered starting 15 minutes before coronary occlusion and continued for 2 hours, terminating 15 minutes after reperfusion. Infarct size was determined 6 hours later. In Protocol B, the conjugated proteins were given 15 minutes before reperfusion and ended simultaneously with reperfusion. Infarct size was measured after 4 days. Infarct size (percentage of area at risk) in control (n = 9) and treated (n = 9) dogs in Protocol A differed between groups: 46.7 +/- 3.5% versus 28.3 +/- 2.9%, respectively (p less than or equal to 0.005); risk regions did not differ: 42.8 +/- 1.5% versus 43.8 +/- 2.1%, respectively. Myocardial salvage also was observed in Protocol B. Infarct size in control (n = 13) and treated (n = 13) groups was 44.2 +/- 2.6% versus 29.2 +/- 1.6%, respectively (p less than or equal to 0.005), with risk regions being 44.4 +/- 1.4% versus 46.0 +/- 1.6% (p = NS). Hemodynamic variables did not differ during the period of coronary artery occlusion. The respective collateral blood flows to the inner two thirds of the ischemic myocardium determined 60 minutes after occlusion were 0.05 +/- 0.01 ml/min/g and 0.06 +/- 0.04 ml/min/g (p = 0.806) for the PEG-ALB and PEG-SOD treated groups, respectively. Infarct size was related inversely to collateral blood flow in the PEG-ALB treated group. This relation shifted downward (analysis of covariance, p = 0.017). Plasma SOD activity in Protocols A sustained for 6 hours. Significant enzymatic activity was present after 4 days in Protocol B. Previous negative studies with native SOD may be related to the short half-life of its free-radical scavenging capacity, which compromises the chances of observing a protective effect after 4 days of reperfusion. The present results support our previous observations, as well as those of other investigators, demonstrating that superoxide dismutase can reduce that component of myocardial injury associated with reperfusion.

Previously, we have demonstrated an increased incidence of lethal ischemic arrhythmias in postinfarction dogs with clinically observable serum digoxin concentrations, and a significant reduction in digitalis-related lethal ischemic arrhythmias after subacute left stellectomy. In the present study, the protective actions of acute beta-adrenoceptor blockade with nadolol, 1.0 mg/kg administered intravenously immediately preceding the induction of posterolateral myocardial ischemia, were assessed in conscious dogs with recent, small anterior myocardial infarctions pretreated with digoxin, 0.0125 mg/kg/day intravenously, for 5 to 7 consecutive days (total n = 11). A cohort of postinfarction dogs pretreated with digoxin alone served as a control group (total n = 26). Pre vs postdigoxin electrophysiologic testing indicated reductions in myocardial refractoriness in ventricular noninfarct and infarct zones in both treatment groups, whereas the administration of nadolol tended to reverse the reductions in ventricular refractoriness. Arrhythmia-related deaths in response to posterolateral myocardial ischemia were reduced from 12 of 20 (60%) in the digoxin control group to 2 of 10 (20%) in the digoxin + nadolol group (p = 0.039). Serum digoxin concentrations (1.29 +/- 0.14 ng/ml vs 1.39 +/- 0.24 ng/ml), underlying anterior myocardial infarct size (6.9 +/- 1.5% vs 4.6 +/- 0.9% of left ventricle), and developing posterolateral myocardial infarct size (22.8 +/- 2.5% vs 17.5 +/- 3.6% of left ventricle) did not differ significantly between the digoxin and digoxin + nadolol groups. Acute beta-adrenoceptor blockade with nadolol appears to reduce digitalis-mediated ischemic postinfarction mortality, possibly because of a salutary increase in ventricular refractoriness.

Pimobendan (UD-CG 115 BS; 4,5-dihydro-6-[2-(4-methoxyphenyl)-1H-benzimidazol-5-yl]-5-methyl- 3(2H)- pyridazinone) is a newly developed, structurally novel compound with positive inotropic as well as coronary and peripheral vasodilator activities. In vitro, pimobendan has been reported to prolong the duration of the cardiac action potential of ventricular myocardial tissue, suggesting the potential for this agent to increase myocardial refractoriness and possibly exert antiarrhythmic activity in vivo. In the present study, the effects of pimobendan upon cardiac electrophysiologic parameters, the induction of ventricular tachycardia by programmed ventricular stimulation, and upon the development of ischemic ventricular fibrillation were assessed in 16 conscious dogs 3 to 5 days after experimental anterior myocardial infarction. The intravenous administration of 0.3 mg/kg pimobendan to postinfarction dogs significantly reduced the rate-corrected QTc and paced QT intervals, and reduced the relative and effective refractory periods in normal noninjured ventricular myocardium. Electrophysiologic parameters in infarcted ventricular myocardium were not altered by pimobendan. Ventricular tachycardia remained inducible early after anterior myocardial infarction in eight of eight pimobendan-treated postinfarction dogs tested. Six of the eight pimobendan-treated animals that had nonsustained tachyarrhythmias elicited as initial responses to baseline programmed stimulation testing had sustained tachycardias induced at postdrug testing, with a reduction in the number of programmed extrastimuli required to induce the postpimobendan tachyarrhythmias occurring in three animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Amlodipine is a dihydropyridine derivative belonging to the group of pharmacologic calcium entry blocking agents and is characterized as having a slow onset and relatively long duration of action with minimal effects on cardiac electrophysiology and myocardial contractility. The protective effect of amlodipine was studied in isolated blood-perfused feline hearts made globally ischemic for 60 minutes followed by reperfusion for 60 minutes. Ischemic-induced alterations of left ventricular developed pressure and complicance were monitored. In 11 control and 7 drug-treated hearts, amlodipine produced significant decreases in myocardial oxygen consumption (6.2 +/- 0.4 to 4.4 +/- 0.4 ml oxygen/min/100 g) and coronary vascular resistance, as assessed by changes in perfusion pressure (120 +/- 1 to 100 +/- 4 mm Hg). Amlodipine administered before the onset of global ischemia decreased the development of ischemic contracture as reflected by a progressive increase in resting left ventricular diastolic pressure. The return of contractile function, 60 minutes afer reperfusion, improved significantly in the amlodipine-treated group compared with controls, and there was better maintenance of the tissue concentration of Na+, Ca2+ and K+. A canine model of regional myocardial ischemia (90 minutes) followed by 6 hours of reperfusion was used to assess the cardioprotective effects of amlodipine, 150 micrograms/kg, administered 15 minutes before reperfusion. Infarct size, expressed as a percentage of the area at risk, was smaller in the amlodipine-treated group (n = 10) than in the control group (n = 10) (34.5 +/- 3.8% vs 45.9 +/- 2.8%, p = 0.027). Risk region size did not differ between groups and both groups were comparable with respect to the hemodynamic parameters of heart rate, blood pressure and rate-pressure product. Amlodipine prevented the gradual reduction in coronary blood flow observed in the control group. It is concluded that amlodipine reduces myocardial ischemic injury by mechanism(s) that may involve a reduction in myocardial oxygen demand as well as by positively influencing transmembrane Ca2+ fluxes during ischemia and reperfusion.