Association of glucagon-like peptide receptor 1 agonist therapy with the presence of gastric contents in fasting patients undergoing endoscopy under anesthesia care: a historical cohort study.

PURPOSE: We aimed to estimate the association of glucagon-like peptide 1 (GLP-1) receptor agonist therapy with the incidence of endoscopically visible gastric contents after preprocedural fasting. METHODS: We reviewed the records of esophagogastroduodenoscopy (EGD) performed at our institution between 2019 and 2023 and determined the presence of residual gastric contents from the procedure notes and saved images. We compared patients taking GLP-1 agonists at the time of the procedure (GLP group, 90 procedures) with patients who started GLP-1 agonist therapy within 1,000 days after undergoing EGD (control, 102 procedures). We excluded emergent procedures without fasting, combined EGD/colonoscopy procedures, and patients with known gastroparesis or previous gastric surgery. We estimated the association between GLP-1 agonist therapy and residual gastric contents with a confounder-adjusted generalized linear mixed effect model. RESULTS: Compared with controls, the GLP cohort had a higher age, American Society of Anesthesiologists' Physical Status, and incidence of nausea and diabetes mellitus. Body mass index and fasting duration were comparable between groups. Visible gastric content was documented in 17 procedures in the GLP group (19%) and in five procedures in the control group (5%), with an associated confounder adjusted odds ratio of 5.8 (95% confidence interval, 1.7 to 19.3; P = 0.004). There were five instances of emergent endotracheal intubation in the GLP group vs one case in control and one case of pulmonary aspiration vs none in control. CONCLUSIONS: In fasting patients, GLP-1 agonist therapy was associated with an increased incidence of residual gastric contents, potentially posing an additional risk of periprocedural pulmonary aspiration.

RéSUMé: OBJECTIF: Notre objectif était d'estimer l'association d'un traitement par agonistes des récepteurs du peptide-1 de type glucagon (glucagon-like peptide 1, GLP-1) avec l'incidence de contenu gastrique visible par endoscopie malgré le jeûne préopératoire. MéTHODE: Nous avons examiné les dossiers des œsophagogastroduodénoscopies (OGD) réalisées dans notre établissement entre 2019 et 2023 et déterminé la présence de contenu gastrique résiduel à partir des notes d'intervention et des images enregistrées. Nous avons comparé les patient·es prenant des agonistes du GLP-1 au moment de l'intervention (groupe GLP, 90 procédures) avec les patient·es qui ont commencé un traitement par agonistes du GLP-1 dans les 1000 jours suivant l'OGD (groupe témoin, 102 procédures). Nous avons exclu les procédures d'urgence sans jeûne, les procédures combinées OGD/coloscopie et les patient·es présentant une gastroparésie connue ou une chirurgie gastrique antérieure. Nous avons estimé l'association entre le traitement par agonistes du récepteur GLP-1 et le contenu gastrique résiduel à l'aide d'un modèle linéaire généralisé à effets mixtes ajusté en fonction des facteurs de confusion. RéSULTATS: Par rapport aux témoins, la cohorte GLP était plus âgée, de statut physique selon l'American Society of Anesthesiologists plus élevé et présentait une incidence plus élevée de nausées et de diabète. L'indice de masse corporelle et la durée du jeûne étaient comparables entre les groupes. Du contenu gastrique visible a été documenté dans 17 procédures dans le groupe GLP (19 %) et dans cinq procédures dans le groupe témoin (5 %), avec un rapport de cotes ajusté associé de 5,8 (intervalle de confiance à 95 %, 1,7 à 19,3; P = 0,004). Il y a eu cinq cas d'intubation endotrachéale urgente dans le groupe GLP vs un cas dans le groupe témoin et un cas d'aspiration pulmonaire vs aucun dans le groupe témoin. CONCLUSION: Chez la patientèle à jeun, le traitement par agonistes des récepteurs du GLP-1 a été associé à une incidence accrue de contenu gastrique résiduel, ce qui pourrait entraîner un risque supplémentaire d'aspiration pulmonaire périprocédurale.

Semaglutide, delayed gastric emptying, and intraoperative pulmonary aspiration: a case report.

PURPOSE: We report a case in which the use of semaglutide for weight loss was associated with delayed gastric emptying and intraoperative pulmonary aspiration of gastric contents. CLINICAL FEATURES: A 42-yr-old patient with Barrett's esophagus underwent repeat upper gastrointestinal endoscopy and ablation of dysplastic mucosa. Two months earlier, the patient had started weekly injections of semaglutide for weight loss. Despite having fasted for 18 hr, and differing from the findings of prior procedures, endoscopy revealed substantial gastric content, which was suctioned before endotracheal intubation. Food remains were removed from the trachea and bronchi using bronchoscopy. The patient was extubated four hours later and remained asymptomatic. CONCLUSION: Patients using semaglutide and other glucagon-like peptide 1 agonists for weight management may require specific precautions during induction of anesthesia to prevent pulmonary aspiration of gastric contents.

RéSUMé: OBJECTIF: Nous rapportons un cas dans lequel l'utilisation de sémaglutide à des fins de perte de poids a été associée à un retard de vidange gastrique et à une aspiration pulmonaire peropératoire du contenu gastrique. CARACTéRISTIQUES CLINIQUES: Un patient de 42 ans souffrant d'un œsophage de Barrett a subi une cinquième endoscopie gastro-intestinale supérieure avec ablation de la muqueuse dysplasique. Deux mois plus tôt, le patient avait commencé à recevoir des injections hebdomadaires de sémaglutide pour perdre du poids. Bien qu'à jeun depuis 18 heures et à la différence des évaluations lors des interventions antérieures, l'endoscopie a révélé un contenu gastrique important, qui a été aspiré avant l'intubation endotrachéale. Les restes de nourriture ont été retirés de la trachée et des bronches par bronchoscopie. Le patient a été extubé quatre heures plus tard et est demeuré asymptomatique. CONCLUSION: Les patients utilisant du sémaglutide et d'autres agonistes du peptide analog au glucagon-1 pour la gestion du poids pourraient nécessiter des précautions spécifiques lors de l'induction de l'anesthésie pour empêcher l'aspiration pulmonaire du contenu gastrique.

CARDIOMYOCYTE REPROGRAMMING IN ANIMAL MODELS OF SEPTIC SHOCK.

ABSTRACT: Cardiomyocyte reprogramming plays a pivotal role in sepsis-induced cardiomyopathy through the induction or overexpression of several factors and enzymes, ultimately leading to the characteristic decrease in cardiac contractility. The initial trigger is the binding of LPS to TLR-2, -3, -4, and -9 and of proinflammatory cytokines, such as TNF, IL-1, and IL-6, to their respective receptors. This induces the nuclear translocation of nuclear factors, such as NF-κB, via activation of MyD88, TRIF, IRAK, and MAPKs. Among the latter, ROS- and estrogen-dependent p38 and ERK 1/2 are proinflammatory, whereas JNK may play antagonistic, anti-inflammatory roles. Nuclear factors induce the synthesis of cytokines, which can amplify the inflammatory signal in a paracrine fashion, and of several effector enzymes, such as NOS-2, NOX-1, and others, which are ultimately responsible for the degradation of cardiomyocyte contractility. In parallel, the downregulation of enzymes involved in oxidative phosphorylation causes metabolic reprogramming, followed by a decrease in ATP production and the release of fragmented mitochondrial DNA, which may augment the process in a positive feedback loop. Other mediators, such as NO, ROS, the enzymes PI3K and Akt, and adrenergic stimulation may play regulatory roles, but not all signaling pathways that mediate cardiac dysfunction of sepsis do that by regulating reprogramming. Transcription may be globally modulated by miRs, which exert protective or amplifying effects. For all these mechanisms, differentiating between modulation of cardiomyocyte reprogramming versus systemic inflammation has been an ongoing but worthwhile experimental challenge.

MECHANISMS OF CARDIAC DYSFUNCTION IN SEPSIS.

ABSTRACT: Studies in animal models of sepsis have elucidated an intricate network of signaling pathways that lead to the dysregulation of myocardial Ca 2+ handling and subsequently to a decrease in cardiac contractile force, in a sex- and model-dependent manner. After challenge with a lethal dose of LPS, male animals show a decrease in cellular Ca 2+ transients (ΔCa i ), with intact myofilament function, whereas female animals show myofilament dysfunction, with intact ΔCa i . Male mice challenged with a low, nonlethal dose of LPS also develop myofilament desensitization, with intact ΔCa i . In the cecal ligation and puncture (CLP) model, the causative mechanisms seem similar to those in the LPS model in male mice and are unknown in female subjects. ΔCa i decrease in male mice is primarily due to redox-dependent inhibition of sarco/endoplasmic reticulum Ca 2+ ATP-ase (SERCA). Reactive oxygen species (ROS) are overproduced by dysregulated mitochondria and the enzymes NADPH/NADH oxidase, cyclooxygenase, and xanthine oxidase. In addition to inhibiting SERCA, ROS amplify cardiomyocyte cytokine production and mitochondrial dysfunction, making the process self-propagating. In contrast, female animals may exhibit a natural redox resilience. Myofilament dysfunction is due to hyperphosphorylation of troponin I, troponin T cleavage by caspase-3, and overproduction of cGMP by NO-activated soluble guanylate cyclase. Depleted, dysfunctional, or uncoupled mitochondria likely synthesize less ATP in both sexes, but the role of energy deficit is not clear. NO produced by NO synthase (NOS)-3 and mitochondrial NOSs, protein kinases and phosphatases, the processes of autophagy and sarco/endoplasmic reticulum stress, and ß-adrenergic insensitivity may also play currently uncertain roles.

Effects of Sodium-Glucose Linked Transporter 2 Inhibition With Ertugliflozin on Mitochondrial Function, Energetics, and Metabolic Gene Expression in the Presence and Absence of Diabetes Mellitus in Mice.

Background Inhibitors of the sodium-glucose linked transporter 2 improve cardiovascular outcomes in patients with or without type 2 diabetes mellitus, but the effects on cardiac energetics and mitochondrial function are unknown. We assessed the effects of sodium-glucose linked transporter 2 inhibition on mitochondrial function, high-energy phosphates, and genes encoding mitochondrial proteins in hearts of mice with and without diet-induced diabetic cardiomyopathy. Methods and Results Mice fed a control diet or a high-fat, high-sucrose diet received ertugliflozin mixed with the diet (0.5 mg/g of diet) for 4 months. Isolated mitochondria were assessed for functional capacity. High-energy phosphates were assessed by 31P nuclear magnetic resonance spectroscopy concurrently with contractile performance in isolated beating hearts. The high-fat, high-sucrose diet caused myocardial hypertrophy, diastolic dysfunction, mitochondrial dysfunction, and impaired energetic response, all of which were prevented by ertugliflozin. With both diets, ertugliflozin caused supernormalization of contractile reserve, as measured by rate×pressure product at high work demand. Likewise, the myocardial gene sets most enriched by ertugliflozin were for oxidative phosphorylation and fatty acid metabolism, both of which were enriched independent of diet. Conclusions Ertugliflozin not only prevented high-fat, high-sucrose-induced pathological cardiac remodeling, but improved contractile reserve and induced the expression of oxidative phosphorylation and fatty acid metabolism gene sets independent of diabetic status. These effects of sodium-glucose linked transporter 2 inhibition on cardiac energetics and metabolism may contribute to improved structure and function in cardiac diseases associated with mitochondrial dysfunction, such as heart failure.

Redox-Resistant SERCA [Sarco(endo)plasmic Reticulum Calcium ATPase] Attenuates Oxidant-Stimulated Mitochondrial Calcium and Apoptosis in Cardiac Myocytes and Pressure Overload-Induced Myocardial Failure in Mice.

BACKGROUND: SERCA [sarco(endo)plasmic reticulum calcium ATPase] is regulated by oxidative posttranslational modifications at cysteine 674 (C674). Because sarcoplasmic reticulum (SR) calcium has been shown to play a critical role in mediating mitochondrial dysfunction in response to reactive oxygen species, we hypothesized that SERCA oxidation at C674 would modulate the effects of reactive oxygen species on mitochondrial calcium and mitochondria-dependent apoptosis in cardiac myocytes. METHODS: Adult rat ventricular myocytes expressing wild-type SERCA2b or a redox-insensitive mutant in which C674 is replaced by serine (C674S) were exposed to H2O2 (100 µmol/Lµ). Free mitochondrial calcium concentration was measured in adult rat ventricular myocytes with a genetically targeted fluorescent probe, and SR calcium content was assessed by measuring caffeine-stimulated release. Mice with heterozygous knock-in of the SERCA C674S mutation were subjected to chronic ascending aortic constriction. RESULTS: In adult rat ventricular myocytes expressing wild-type SERCA, H2O2 caused a 25% increase in mitochondrial calcium concentration that was associated with a 50% decrease in SR calcium content, both of which were prevented by the ryanodine receptor inhibitor tetracaine. In cells expressing the C674S mutant, basal SR calcium content was decreased by 31% and the H2O2-stimulated rise in mitochondrial calcium concentration was attenuated by 40%. In wild-type cells, H2O2 caused cytochrome c release and apoptosis, both of which were prevented in C674S-expressing cells. In myocytes from SERCA knock-in mice, basal SERCA activity and SR calcium content were decreased. To test the effect of C674 oxidation on apoptosis in vivo, SERCA knock-in mice were subjected to chronic ascending aortic constriction. In wild-type mice, ascending aortic constriction caused myocyte apoptosis, LV dilation, and systolic failure, all of which were inhibited in SERCA knock-in mice. CONCLUSIONS: Redox activation of SERCA C674 regulates basal SR calcium content, thereby mediating the pathologic reactive oxygen species-stimulated rise in mitochondrial calcium required for myocyte apoptosis and myocardial failure.

Myocardial Redox Hormesis Protects the Heart of Female Mice in Sepsis.

Mice challenged with lipopolysaccharide develop cardiomyopathy in a sex and redox-dependent fashion. Here we extended these studies to the cecal ligation and puncture (CLP) model.We compared male and female FVB mice (wild type, WT) and transgenic littermates overexpressing myocardial catalase (CAT). CLP induced 100% mortality within 4 days, with similar mortality rates in male and female WT and CAT mice. 24 h after CLP, isolated (Langendorff) perfused hearts showed depressed contractility in WT male mice, but not in male CAT or female WT and CAT mice. In WT male mice, CLP induced a depression of cardiomyocyte sarcomere shortening (ΔSS) and calcium transients (ΔCai), and the inhibition of the sarcoplasmic reticulum Ca ATPase (SERCA). These deficits were associated with overexpression of NADPH-dependent oxidase (NOX)-1, NOX-2, and cyclooxygenase 2 (COX-2), and were partially prevented in male CAT mice. Female WT mice showed unchanged ΔSS, ΔCai, and SERCA function after CLP. At baseline, female WT mice showed partially depressed ΔSS, ΔCai, and SERCA function, as compared with male WT mice, which were associated with NOX-1 overexpression and were prevented in CAT female mice.In conclusion, in male WT mice, septic shock induces myocardial NOX-1, NOX-2, and COX-2, and redox-dependent dysregulation of myocardial Ca transporters. Female WT mice are resistant to CLP-induced cardiomyopathy, despite increased NOX-1 and COX-2 expression, suggesting increased antioxidant capacity. Female resistance occurred in association with NOX-1 overexpression and signs of increased oxidative signaling at baseline, indicating the presence of a protective myocardial redox hormesis mechanism.

Up-regulation of Intracellular Calcium Handling Underlies the Recovery of Endotoxemic Cardiomyopathy in Mice.

BACKGROUND: In surviving patients, sepsis-induced cardiomyopathy is spontaneously reversible. In the absence of any experimental data, it is generally thought that cardiac recovery in sepsis simply follows the remission of systemic inflammation. Here the authors aimed to identify the myocardial mechanisms underlying cardiac recovery in endotoxemic mice. METHODS: Male C57BL/6 mice were challenged with lipopolysaccharide (7 µg/g, intraperitoneally) and followed for 12 days. The authors assessed survival, cardiac function by echocardiography, sarcomere shortening, and calcium transients (with fura-2-acetoxymethyl ester) in electrically paced cardiomyocytes (5 Hz, 37°C) and myocardial protein expression by immunoblotting. RESULTS: Left ventricular ejection fraction, cardiomyocyte sarcomere shortening, and calcium transients were depressed 12 h after lipopolysaccharide challenge, started to recover by 24 h (day 1), and were back to baseline at day 3. The recovery of calcium transients at day 3 was associated with the up-regulation of the sarcoplasmic reticulum calcium pump to 139 ± 19% (mean ± SD) of baseline and phospholamban down-regulation to 35 ± 20% of baseline. At day 6, calcium transients were increased to 123 ± 31% of baseline, associated with increased sarcoplasmic reticulum calcium load (to 126 ± 32% of baseline, as measured with caffeine) and inhibition of sodium/calcium exchange (to 48 ± 12% of baseline). CONCLUSIONS: In mice surviving lipopolysaccharide challenge, the natural recovery of cardiac contractility was associated with the up-regulation of cardiomyocyte calcium handling above baseline levels, indicating the presence of an active myocardial recovery process, which included sarcoplasmic reticulum calcium pump activation, the down-regulation of phospholamban, and sodium/calcium exchange inhibition.

Distinct Myocardial Mechanisms Underlie Cardiac Dysfunction in Endotoxemic Male and Female Mice.

In male mice, sepsis-induced cardiomyopathy develops as a result of dysregulation of myocardial calcium (Ca) handling, leading to depressed cellular Ca transients (ΔCai). ΔCai depression is partially due to inhibition of sarcoplasmic reticulum Ca ATP-ase (SERCA) via oxidative modifications, which are partially opposed by cGMP generated by the enzyme soluble guanylyl cyclase (sGC). Whether similar mechanisms underlie sepsis-induced cardiomyopathy in female mice is unknown.Male and female C57Bl/6J mice (WT), and mice deficient in the sGC α1 subunit activity (sGCα1), were challenged with lipopolysaccharide (LPS, ip). LPS induced mouse death and cardiomyopathy (manifested as the depression of left ventricular ejection fraction by echocardiography) to a similar degree in WT male, WT female, and sGCα1 male mice, but significantly less in sGCα1 female mice. We measured sarcomere shortening and ΔCai in isolated, externally paced cardiomyocytes, at 37°C. LPS depressed sarcomere shortening in both WT male and female mice. Consistent with previous findings, in male mice, LPS induced a decrease in ΔCai (to 30 ±â€Š2% of baseline) and SERCA inhibition (manifested as the prolongation of the time constant of Ca decay, τCa, to 150 ±â€Š5% of baseline). In contrast, in female mice, the depression of sarcomere shortening induced by LPS occurred in the absence of any change in ΔCai, or SERCA activity. This suggested that, in female mice, the causative mechanism lies downstream of the Ca transients, such as a decrease in myofilament sensitivity for Ca. The depression of sarcomere shortening shortening after LPS was less severe in female sGCα1 mice than in WT female mice, indicating that cGMP partially mediates cardiomyocyte dysfunction.These results suggest, therefore, that LPS-induced cardiomyopathy develops through distinct sex-specific myocardial mechanisms. While in males LPS induces sGC-independent decrease in ΔCai, in female mice LPS acts downstream of ΔCai, possibly via sGC-dependent myofilament dysfunction.

Dysregulation of intracellular calcium transporters in animal models of sepsis-induced cardiomyopathy.

Sepsis-induced cardiomyopathy (SIC) develops as the result of myocardial calcium (Ca) dysregulation. Here we reviewed all published studies that quantified the dysfunction of intracellular Ca transporters and the myofilaments in animal models of SIC. Cardiomyocytes isolated from septic animals showed, invariably, a decreased twitch amplitude, which is frequently caused by a decrease in the amplitude of cellular Ca transients (ΔCai) and sarcoplasmic reticulum (SR) Ca load (CaSR). Underlying these deficits, the L-type Ca channel is downregulated, through mechanisms that may involve adrenomedullin-mediated redox signaling. The SR Ca pump is also inhibited, through oxidative modifications (sulfonylation) of one reactive thiol group (on Cys) and/or modulation of phospholamban. Diastolic Ca leak of ryanodine receptors is frequently increased. In contrast, Na/Ca exchange inhibition may play a partially compensatory role by increasing CaSR and ΔCai. The action potential is usually shortened. Myofilaments show a bidirectional regulation, with decreased Ca sensitivity in milder forms of disease (due to troponin I hyperphosphorylation) and an increase (redox mediated) in more severe forms. Most deficits occurred similarly in two different disease models, induced by either intraperitoneal administration of bacterial lipopolysaccharide or cecal ligation and puncture. In conclusion, substantial cumulative evidence implicates various Ca transporters and the myofilaments in SIC pathology. What is less clear, however, are the identity and interplay of the signaling pathways that are responsible for Ca transporters dysfunction. With few exceptions, all studies we found used solely male animals. Identifying sex differences in Ca dysregulation in SIC becomes, therefore, another priority.

Lipopolysaccharide and cytokines inhibit rat cardiomyocyte contractility in vitro.

BACKGROUND: Sepsis-induced cardiomyopathy (SIC) is thought to be the result of detrimental effects of inflammatory mediators on the cardiac muscle. Here we studied the effects of prolonged (24 ± 4 h) exposure of adult rat ventricular myocytes (ARVM) to bacterial lipopolysaccharide (LPS) and inflammatory cytokines tumor necrosis factor (TNF) and interleukins-1 (IL-1) and IL-6. MATERIALS AND METHODS: We measured sarcomere shortening (SS) and cellular calcium (Ca(2+)) transients (ΔCai, with fura-2 AM) in isolated cardiomyocytes externally paced at 5 Hz at 37°C. RESULTS: SS decreased after incubation with LPS (100 µg/mL), IL-1 (100 ng/mL), and IL-6 (30 ng/mL), but not with lesser doses of these mediators, or TNF (10-100 ng/mL). A combination of LPS (100 µg/mL), TNF, IL-1, and IL-6 (each 100 ng/mL; i.e., "Cytomix-100") induced a maximal decrease in SS and ΔCai. Sarcoplasmic reticulum (SR) Ca(2+) load (CaSR, measured with caffeine) was unchanged by Cytomix-100; however, SR fractional release (ΔCai/CaSR) was decreased. Underlying these effects, Ca(2+) influx into the cell (via L-type Ca(2+) channels, LTCC) and Ca(2+) extrusion via Na(+)/Ca(2+) exchange were decreased by Cytomix-100. SR Ca(2+) pump (SERCA) (SR Ca(2+) ATPase) was not affected. CONCLUSIONS: Prolonged exposure of ARVM to a mixture of LPS and inflammatory cytokines inhibits cell contractility. The effect is mediated by the inhibition of Ca(2+) influx via LTCC, and partially opposed by the inhibition of Na(+)/Ca(2+) exchange. Because both mechanisms are commonly seen in animal models of SIC, we conclude that prolonged challenge with Cytomix-100 of ARVM may represent an accurate in vitro model for SIC.

SERCA Cys674 sulphonylation and inhibition of L-type Ca2+ influx contribute to cardiac dysfunction in endotoxemic mice, independent of cGMP synthesis.

The goal of this study was to identify the cellular mechanisms responsible for cardiac dysfunction in endotoxemic mice. We aimed to differentiate the roles of cGMP [produced by soluble guanylyl cyclase (sGC)] versus oxidative posttranslational modifications of Ca(2+) transporters. C57BL/6 mice [wild-type (WT) mice] were administered lipopolysaccharide (LPS; 25 µg/g ip) and euthanized 12 h later. Cardiomyocyte sarcomere shortening and Ca(2+) transients (ΔCai) were depressed in LPS-challenged mice versus baseline. The time constant of Ca(2+) decay (τCa) was prolonged, and sarcoplasmic reticulum Ca(2+) load (CaSR) was depressed in LPS-challenged mice (vs. baseline), indicating decreased activity of sarco(endo)plasmic Ca(2+)-ATPase (SERCA). L-type Ca(2+) channel current (ICa,L) was also decreased after LPS challenge, whereas Na(+)/Ca(2+) exchange activity, ryanodine receptors leak flux, or myofilament sensitivity for Ca(2+) were unchanged. All Ca(2+)-handling abnormalities induced by LPS (the decrease in sarcomere shortening, ΔCai, CaSR, ICa,L, and τCa prolongation) were more pronounced in mice deficient in the sGC main isoform (sGCα1(-/-) mice) versus WT mice. LPS did not alter the protein expression of SERCA and phospholamban in either genotype. After LPS, phospholamban phosphorylation at Ser(16) and Thr(17) was unchanged in WT mice and was increased in sGCα1(-/-) mice. LPS caused sulphonylation of SERCA Cys(674) (as measured immunohistochemically and supported by iodoacetamide labeling), which was greater in sGCα1(-/-) versus WT mice. Taken together, these results suggest that cardiac Ca(2+) dysregulation in endotoxemic mice is mediated by a decrease in L-type Ca(2+) channel function and oxidative posttranslational modifications of SERCA Cys(674), with the latter (at least) being opposed by sGC-released cGMP.

Anesthesia for tracheal resection and reconstruction.

Tracheal resection and reconstruction (TRR) is the treatment of choice for most patients with tracheal stenosis or tracheal tumors. Anesthesia for TRR offers distinct challenges, especially for the less experienced practitioner. This article explores the preoperative assessment, strategies for induction and emergence from anesthesia, the essential coordination between the surgical and anesthesia teams during airway excision and anastomosis, and postoperative care. The most common complications are reviewed. Targeted readership is practitioners with less extensive experience in managing airway surgery cases. As such, the article focuses first on the most common proximal tracheal resection. Final sections discuss specific considerations for more complicated cases.

The management and outcome of documented intraoperative heart rate-related electrocardiographic changes.

OBJECTIVES: The authors analyzed surgical cases in which electrocardiographic (ECG) signs of cardiac ischemia were noted to be precipitated by increases in heart rate (ie, heart rate-related ECG changes [REC]). The authors aimed to find REC incidence, specificity for coronary artery disease (CAD), and the outcome associated with different management strategies. DESIGN: A retrospective review. SETTING: A university hospital, tertiary care. PARTICIPANTS: Patients undergoing surgery under anesthesia. INTERVENTIONS: A chart review. MEASUREMENTS: The authors searched 158,252 anesthesia electronic records for comments noting REC (ie, ST-segment or T-wave changes). After excluding cases with potentially confounding conditions (eg, hypotension, hyperkalemia, and so on), 26 cases were analyzed. RESULTS: REC commonly was precipitated by anesthesia-related events (ie, intubation, extubation, and treatment of bradycardia). In 24 cases, REC was managed by prompt heart rate reduction using ß-blocker agents, opioids, and/or cardioversion in the addition to the removal of stimulus. Only 1 case had a copy of the ECG printed. Two cases were aborted, 1 was shortened and 23 proceeded without change. Postoperative troponin T levels were checked, and cardiology consultation was obtained in selected cases and led to further cardiac evaluation in 6 cases. Postoperative myocardial infarction developed in only 1 patient in whom the ECG changes were allowed to persist throughout the case. CONCLUSIONS: This incidence of reported REC was much lower than the previously reported incidence of ischemia-related ECG changes, suggesting that the largest proportion of events go unnoticed. In many patients, subsequent cardiology workup did not confirm the existence of clinically significant CAD.