lipid-a and Myocardial-Ischemia

Unprecedented community containment measures were taken following the recent outbreak of COVID-19 in Italy. The aim of the study was to explore the self-reported future compliance of citizens with such measures and its relationship with potentially impactful psychological variables.. An online survey was completed by 931 people (18-76 years) distributed across the Italian territory. In addition to demographics, five dimensions were measured: self-reported compliance with containment measures over time (today, at 7, 14, 30, 60, 90, and 180 days from now) at three hypothetical risk levels (10, 50, 90% of likelihood of contracting the COVID-19), perceived risk, generalized anxiety, intolerance of uncertainty, and relevance of several psychological needs whose satisfaction is currently precluded.. The duration of containment measures plays a crucial role in tackling the spread of the disease as people will be less compliant over time. Psychological needs of citizens impacting on the compliance should be taken into account when planning an easing of the lockdown, along with interventions for protecting vulnerable groups from mental distress.. La apendicitis aguda (AA) es la urgencia quirúrgica abdominal más frecuente. No encontramos estudios específicos que evalúen el impacto de la pandemia causada por el coronavirus 2 (SARS-Cov-2) sobre la AA y su tratamiento quirúrgico. Analizamos la influencia de esta nueva patología sobre la AA.. Estudio observacional retrospectivo en pacientes intervenidos por AA desde enero hasta abril de 2020. Fueron clasificados según el momento de la apendicectomía, antes de la declaración del estado de alarma (Pre-COVID19) y después de la declaración del estado de alarma (Post-COVID19) en España. Se evaluaron variables demográficas, duración de la sintomatología, tipo de apendicitis, tiempo quirúrgico, estancia hospitalaria y complicaciones postoperatorias.. La pandemia por SARS-Cov-2 influye en el momento de diagnóstico de la apendicitis, así como en su grado de evolución y estancia hospitalaria. La peritonitis fue lo más frecuentemente observado. Una sospecha y orientación clínica más temprana, es necesaria para evitar un manejo inadecuado de este trastorno quirúrgico común.. The primary outcome is improvement in PaO. Findings will provide timely information on the safety, efficacy, and optimal dosing of t-PA to treat moderate/severe COVID-19-induced ARDS, which can be rapidly adapted to a phase III trial (NCT04357730; FDA IND 149634).. None.. The gut barrier is crucial in cirrhosis in preventing infection-causing bacteria that normally live in the gut from accessing the liver and other organs via the bloodstream. Herein, we characterised gut inflammation by measuring different markers in stool samples from patients at different stages of cirrhosis and comparing this to healthy people. These markers, when compared with equivalent markers usually measured in blood, were found to be very different in pattern and absolute levels, suggesting that there is significant gut inflammation in cirrhosis related to different immune system pathways to that seen outside of the gut. This provides new insights into gut-specific immune disturbances that predispose to complications of cirrhosis, and emphasises that a better understanding of the gut-liver axis is necessary to develop better targeted therapies.. La surveillance de l’intervalle QT a suscité beaucoup d’intérêt durant la pandémie de la COVID-19 en raison de l’utilisation de médicaments prolongeant l’intervalle QT et les préoccupations quant à la transmission virale par les électrocardiogrammes (ECG) en série. Nous avons posé l’hypothèse que la surveillance en continu de l’intervalle QT par télémétrie était associée à une meilleure détection des épisodes de prolongation de l’intervalle QT.. Nous avons introduit la télémétrie cardiaque en continu (TCC) à l’aide d’un algorithme de surveillance automatisée de l’intervalle QT dans nos unités de COVID-19. Les mesures automatisées quotidiennes de l’intervalle QT corrigé (auto-QTc) en fonction de la fréquence cardiaque maximale ont été enregistrées. Nous avons comparé la proportion des épisodes de prolongation marquée de l’intervalle QTc (QTc long), définie par un intervalle QTc ≥ 500 ms, chez les patients montrant une suspicion de COVID-19 ou ayant la COVID-19 qui avaient été admis avant et après la mise en place de la TCC (groupe témoin. La surveillance en continu de l’intervalle QT est supérieure à la norme de soins dans la détection des épisodes de QTc long et exige peu d’ECG. La réponse clinique aux épisodes de QTc long est sous-optimale.. Exposure to a model wildfire air pollution source modifies cardiovascular responses to HC challenge, suggesting air pollution sensitizes the body to systemic triggers.. Though the majority of HIV-infected adults who were on HAART had shown viral suppression, the rate of suppression was sub-optimal according to the UNAIDS 90-90-90 target to help end the AIDS pandemic by 2020. Nonetheless, the rate of immunological recovery in the study cohort was low. Hence, early initiation of HAART should be strengthened to achieve good virological suppression and immunological recovery.. Dust in Egyptian laying hen houses contains high concentrations of microorganisms and endotoxins, which might impair the health of birds and farmers when inhaled. Furthermore, laying hens in Egypt seem to be a reservoir for ESBL-producing Enterobacteriaceae. Thus, farmers are at risk of exposure to ESBL-producing bacteria, and colonized hens might transmit these bacteria into the food chain.. The lack of significant differences in the absolute changes and relative ratios of injury and repair biomarkers by contrast-associated AKI status suggests that the majority of mild contrast-associated AKI cases may be driven by hemodynamic changes at the kidney.. Most comparisons for different outcomes are based on very few studies, mostly low-powered, with an overall low CoE. Thus, the available evidence is considered insufficient to either support or refute CH effectiveness or to recommend one ICM over another. Therefore, further well-designed, larger RCTs are required.. PROSPERO database Identifier: CRD42016041953.. Untouched root canal at cross-section perimeter, the Hero 642 system showed 41.44% ± 5.62% and Reciproc R40 58.67% ± 12.39% without contact with instruments. Regarding the untouched area, Hero 642 system showed 22.78% ± 6.42% and Reciproc R40 34.35% ± 8.52%. Neither instrument achieved complete cross-sectional root canal debridement. Hero 642 system rotary taper 0.02 instruments achieved significant greater wall contact perimeter and area compared to reciprocate the Reciproc R40 taper 0.06 instrument.. Hero 642 achieved higher wall contact perimeter and area but, regardless of instrument size and taper, vital pulp during. The functional properties of the main mechanisms involved in the control of muscle Ca. This study showed that the anti-inflammatory effect of the iron-responsive product DHA in arthritis can be monitored by an iron-like radioactive tracer (. Attenuated vascular reactivity during pregnancy suggests that the systemic vasodilatory state partially depletes nitric oxide bioavailability. Preliminary data support the potential for MRI to identify vascular dysfunction in vivo that underlies PE. Level of Evidence 2 Technical Efficacy Stage 1 J. MAGN. RESON. IMAGING 2021;53:447-455.. La evaluación de riesgo es importante para predecir los resultados postoperatorios en pacientes con cáncer gastroesofágico. Este estudio de cohortes tuvo como objetivo evaluar los cambios en la composición corporal durante la quimioterapia neoadyuvante e investigar su asociación con complicaciones postoperatorias. MÉTODOS: Los pacientes consecutivos con cáncer gastroesofágico sometidos a quimioterapia neoadyuvante y cirugía con intención curativa entre 2016 y 2019, identificados a partir de una base de datos específica, se incluyeron en el estudio. Se utilizaron las imágenes de tomografía computarizada, antes y después de la quimioterapia neoadyuvante, para evaluar el índice de masa muscular esquelética, la sarcopenia y el índice de grasa visceral y subcutánea.. In this in vitro premature infant lung model, HF oscillation of BCPAP was associated with improved CO. Our results showed that HPC significantly promotes neurogenesis after MCAO and ameliorates neuronal injury.. Inflammatory markers are highly related to signs of systemic hypoperfusion in CS. Moreover, high PCT and IL-6 levels are associated with poor prognosis.. These findings indicate that Tetrapleura tetraptera fruit has a protective potential against stroke through modulation of redox and electrolyte imbalances, and attenuation of neurotransmitter dysregulation and other neurochemical dysfunctions. Tetrapleura tetraptera fruit could be a promising source for the discovery of bioactives for stroke therapy.

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In comparison with ischemic preconditioning, MLA-mediated cardioprotection seems to show numerous common features. Like ischemia, MLA induces a first and second window (biphasic profile) of heightened tolerance to ischemia. As with delayed ischemic preconditioning, MLA protects against infarction, stunning, and arrhythmias associated with ischemia-reperfusion. In contrast with acute ischemic preconditioning, MLA reduces infarction and stunning. A role has been demonstrated for nitric oxide synthase and KATP channel activation in the mechanism of delayed preconditioning induced by ischemia and by MLA. Regarding acute preconditioning, kinase and KATP channel activation have been implicated as involved in the mechanism of ischemic preconditioning and also in MLA cardioprotection. Use of MLA or related compounds as cardioprotectants may represent a method for inducing acute tolerance to ischemia-reperfusion injury manifested as infarction or stunning, with the added benefit of a sustained delayed cardioprotective state being achieved.

Topics: Adaptation, Physiological; Animals; Endotoxins; Heart; Humans; Ischemic Preconditioning, Myocardial; Lipid A; Myocardial Ischemia

As the mechanism of ischemic preconditioning unfolds, various strategies for inducing pharmacologic preconditioning become apparent. Adenosine receptor agonists, KATP channel activators, and endothelial-neutrophil adhesion antagonists have enjoyed cardioprotective activity against ischemia/reperfusion injury in at least some preclinical models. Monophosphoryl lipid A (MLA), a structural derivative of the pharmacophore of endotoxin, enjoys an improved therapeutic index in relation to the parent biological product. MLA has found clinical application as a vaccine adjuvant and protects from sepsis and septic shock in the preclinical setting. In animal models of myocardial ischemia/reperfusion injury, pretreatment 12-24 hours prior to ischemia with a single IV bolus injection of MLA limits infarct size 50 to 75 percent in standard canine and rabbit models at doses of 10-35 micrograms/kg. Regional myocardial stunning following multiple 5-minute ischemic episodes as assessed by segment shortening is reduced in dogs pretreated 24 but not 1 hour prior to ischemia. Global cardiac function, as evaluated by pressure-volume constructs generated in dogs being weaned from cardiopulmonary bypass, recovers more quickly in animals pretreated with MLA. Cardiac protection in various models is associated with preservation of ATP during ischemia, induction of 5' nucleotidase and enhancement of calcium reuptake by SR during reperfusion. Limitation of infarct size by MLA in dogs and rabbits can be reversed by the administration of glibenclamide just prior to ischemia, suggesting a role for KATP channel opening during the first minutes of sustained ischemia. A clinical formulation of MLA (MPL-C) is currently undergoing clinical investigation in the Phase II setting in coronary artery bypass surgical patients. MLA may represent a novel means of inducing pharmacologic preconditioning, with potential for clinical application as a pretreatment before planned myocardial ischemia.

Topics: Adjuvants, Immunologic; Animals; Dogs; Humans; Lipid A; Myocardial Infarction; Myocardial Ischemia; Myocardial Stunning; Rabbits

Unprecedented community containment measures were taken following the recent outbreak of COVID-19 in Italy. The aim of the study was to explore the self-reported future compliance of citizens with such measures and its relationship with potentially impactful psychological variables.. An online survey was completed by 931 people (18-76 years) distributed across the Italian territory. In addition to demographics, five dimensions were measured: self-reported compliance with containment measures over time (today, at 7, 14, 30, 60, 90, and 180 days from now) at three hypothetical risk levels (10, 50, 90% of likelihood of contracting the COVID-19), perceived risk, generalized anxiety, intolerance of uncertainty, and relevance of several psychological needs whose satisfaction is currently precluded.. The duration of containment measures plays a crucial role in tackling the spread of the disease as people will be less compliant over time. Psychological needs of citizens impacting on the compliance should be taken into account when planning an easing of the lockdown, along with interventions for protecting vulnerable groups from mental distress.. La apendicitis aguda (AA) es la urgencia quirúrgica abdominal más frecuente. No encontramos estudios específicos que evalúen el impacto de la pandemia causada por el coronavirus 2 (SARS-Cov-2) sobre la AA y su tratamiento quirúrgico. Analizamos la influencia de esta nueva patología sobre la AA.. Estudio observacional retrospectivo en pacientes intervenidos por AA desde enero hasta abril de 2020. Fueron clasificados según el momento de la apendicectomía, antes de la declaración del estado de alarma (Pre-COVID19) y después de la declaración del estado de alarma (Post-COVID19) en España. Se evaluaron variables demográficas, duración de la sintomatología, tipo de apendicitis, tiempo quirúrgico, estancia hospitalaria y complicaciones postoperatorias.. La pandemia por SARS-Cov-2 influye en el momento de diagnóstico de la apendicitis, así como en su grado de evolución y estancia hospitalaria. La peritonitis fue lo más frecuentemente observado. Una sospecha y orientación clínica más temprana, es necesaria para evitar un manejo inadecuado de este trastorno quirúrgico común.. The primary outcome is improvement in PaO. Findings will provide timely information on the safety, efficacy, and optimal dosing of t-PA to treat moderate/severe COVID-19-induced ARDS, which can be rapidly adapted to a phase III trial (NCT04357730; FDA IND 149634).. None.. The gut barrier is crucial in cirrhosis in preventing infection-causing bacteria that normally live in the gut from accessing the liver and other organs via the bloodstream. Herein, we characterised gut inflammation by measuring different markers in stool samples from patients at different stages of cirrhosis and comparing this to healthy people. These markers, when compared with equivalent markers usually measured in blood, were found to be very different in pattern and absolute levels, suggesting that there is significant gut inflammation in cirrhosis related to different immune system pathways to that seen outside of the gut. This provides new insights into gut-specific immune disturbances that predispose to complications of cirrhosis, and emphasises that a better understanding of the gut-liver axis is necessary to develop better targeted therapies.. La surveillance de l’intervalle QT a suscité beaucoup d’intérêt durant la pandémie de la COVID-19 en raison de l’utilisation de médicaments prolongeant l’intervalle QT et les préoccupations quant à la transmission virale par les électrocardiogrammes (ECG) en série. Nous avons posé l’hypothèse que la surveillance en continu de l’intervalle QT par télémétrie était associée à une meilleure détection des épisodes de prolongation de l’intervalle QT.. Nous avons introduit la télémétrie cardiaque en continu (TCC) à l’aide d’un algorithme de surveillance automatisée de l’intervalle QT dans nos unités de COVID-19. Les mesures automatisées quotidiennes de l’intervalle QT corrigé (auto-QTc) en fonction de la fréquence cardiaque maximale ont été enregistrées. Nous avons comparé la proportion des épisodes de prolongation marquée de l’intervalle QTc (QTc long), définie par un intervalle QTc ≥ 500 ms, chez les patients montrant une suspicion de COVID-19 ou ayant la COVID-19 qui avaient été admis avant et après la mise en place de la TCC (groupe témoin. La surveillance en continu de l’intervalle QT est supérieure à la norme de soins dans la détection des épisodes de QTc long et exige peu d’ECG. La réponse clinique aux épisodes de QTc long est sous-optimale.. Exposure to a model wildfire air pollution source modifies cardiovascular responses to HC challenge, suggesting air pollution sensitizes the body to systemic triggers.. Though the majority of HIV-infected adults who were on HAART had shown viral suppression, the rate of suppression was sub-optimal according to the UNAIDS 90-90-90 target to help end the AIDS pandemic by 2020. Nonetheless, the rate of immunological recovery in the study cohort was low. Hence, early initiation of HAART should be strengthened to achieve good virological suppression and immunological recovery.. Dust in Egyptian laying hen houses contains high concentrations of microorganisms and endotoxins, which might impair the health of birds and farmers when inhaled. Furthermore, laying hens in Egypt seem to be a reservoir for ESBL-producing Enterobacteriaceae. Thus, farmers are at risk of exposure to ESBL-producing bacteria, and colonized hens might transmit these bacteria into the food chain.. The lack of significant differences in the absolute changes and relative ratios of injury and repair biomarkers by contrast-associated AKI status suggests that the majority of mild contrast-associated AKI cases may be driven by hemodynamic changes at the kidney.. Most comparisons for different outcomes are based on very few studies, mostly low-powered, with an overall low CoE. Thus, the available evidence is considered insufficient to either support or refute CH effectiveness or to recommend one ICM over another. Therefore, further well-designed, larger RCTs are required.. PROSPERO database Identifier: CRD42016041953.. Untouched root canal at cross-section perimeter, the Hero 642 system showed 41.44% ± 5.62% and Reciproc R40 58.67% ± 12.39% without contact with instruments. Regarding the untouched area, Hero 642 system showed 22.78% ± 6.42% and Reciproc R40 34.35% ± 8.52%. Neither instrument achieved complete cross-sectional root canal debridement. Hero 642 system rotary taper 0.02 instruments achieved significant greater wall contact perimeter and area compared to reciprocate the Reciproc R40 taper 0.06 instrument.. Hero 642 achieved higher wall contact perimeter and area but, regardless of instrument size and taper, vital pulp during. The functional properties of the main mechanisms involved in the control of muscle Ca. This study showed that the anti-inflammatory effect of the iron-responsive product DHA in arthritis can be monitored by an iron-like radioactive tracer (. Attenuated vascular reactivity during pregnancy suggests that the systemic vasodilatory state partially depletes nitric oxide bioavailability. Preliminary data support the potential for MRI to identify vascular dysfunction in vivo that underlies PE. Level of Evidence 2 Technical Efficacy Stage 1 J. MAGN. RESON. IMAGING 2021;53:447-455.. La evaluación de riesgo es importante para predecir los resultados postoperatorios en pacientes con cáncer gastroesofágico. Este estudio de cohortes tuvo como objetivo evaluar los cambios en la composición corporal durante la quimioterapia neoadyuvante e investigar su asociación con complicaciones postoperatorias. MÉTODOS: Los pacientes consecutivos con cáncer gastroesofágico sometidos a quimioterapia neoadyuvante y cirugía con intención curativa entre 2016 y 2019, identificados a partir de una base de datos específica, se incluyeron en el estudio. Se utilizaron las imágenes de tomografía computarizada, antes y después de la quimioterapia neoadyuvante, para evaluar el índice de masa muscular esquelética, la sarcopenia y el índice de grasa visceral y subcutánea.. In this in vitro premature infant lung model, HF oscillation of BCPAP was associated with improved CO. Our results showed that HPC significantly promotes neurogenesis after MCAO and ameliorates neuronal injury.. Inflammatory markers are highly related to signs of systemic hypoperfusion in CS. Moreover, high PCT and IL-6 levels are associated with poor prognosis.. These findings indicate that Tetrapleura tetraptera fruit has a protective potential against stroke through modulation of redox and electrolyte imbalances, and attenuation of neurotransmitter dysregulation and other neurochemical dysfunctions. Tetrapleura tetraptera fruit could be a promising source for the discovery of bioactives for stroke therapy.

Topics: 3T3-L1 Cells; A Kinase Anchor Proteins; Acetates; Achilles Tendon; Acute Kidney Injury; Acute Pain; Acyclic Monoterpenes; Adenine Nucleotides; Adhesins, Escherichia coli; Adipocytes; Adipocytes, Brown; Adipogenesis; Administration, Inhalation; Administration, Oral; Adrenal Cortex Hormones; Adsorption; Adult; Aeromonas hydrophila; Africa; Aged; Aged, 80 and over; Agrobacterium tumefaciens; Air; Air Pollutants; Air Pollution; Air Pollution, Indoor; Algorithms; Alkaloids; Alkynes; Allosteric Regulation; Amines; Amino Acid Sequence; Amino Acids; Amino Acids, Branched-Chain; Aminoisobutyric Acids; Aminopyridines; Amyotrophic Lateral Sclerosis; Anaerobic Threshold; Angiography; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Animal Distribution; Animal Feed; Animal Nutritional Physiological Phenomena; Animals; Ankle Joint; Anti-Bacterial Agents; Anti-HIV Agents; Anti-Inflammatory Agents; Antibodies, Bacterial; Antifungal Agents; Antimalarials; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Antioxidants; Antiretroviral Therapy, Highly Active; Antiviral Agents; Aotidae; Apelin; Apoptosis; Arabidopsis Proteins; Argentina; Arginine; Artemisinins; Arthritis, Experimental; Arthritis, Rheumatoid; Arthroscopy; Aspergillus; Aspergillus niger; Asteraceae; Asthma; ATP Binding Cassette Transporter, Subfamily B, Member 1; ATP Binding Cassette Transporter, Subfamily G, Member 2; Auditory Cortex; Autoantibodies; Autophagy; Bacteria; Bacterial Infections; Bacterial Proteins; Bacterial Typing Techniques; Base Composition; Base Sequence; Basketball; Beclin-1; Benzhydryl Compounds; Benzimidazoles; Benzo(a)pyrene; Benzofurans; Benzoxazines; Bereavement; beta Catenin; beta-Lactamase Inhibitors; beta-Lactamases; beta-Lactams; Betacoronavirus; Betaine; Binding Sites; Biofilms; Biological Assay; Biological Availability; Biological Evolution; Biomarkers; Biomechanical Phenomena; Biopolymers; Biopsy; Bismuth; Blood Glucose; Blood Platelets; Blood Pressure; Body Composition; Body Weight; Bone Marrow; Bone Marrow Cells; Bone Regeneration; Boron; Botrytis; Brain Ischemia; Brain Neoplasms; Brain-Derived Neurotrophic Factor; Brazil; Breast Neoplasms; Breath Tests; Bronchoalveolar Lavage Fluid; Burkholderia; C-Reactive Protein; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Calcification, Physiologic; Calcium; Calcium Signaling; Calorimetry, Differential Scanning; Cameroon; Camptothecin; Candida; Candida albicans; Capillaries; Carbapenem-Resistant Enterobacteriaceae; Carbapenems; Carbohydrate Conformation; Carbon; Carbon Dioxide; Carbon Isotopes; Carcinoma, Ovarian Epithelial; Cardiac Output; Cardiomyopathy, Hypertrophic; Cardiotonic Agents; Cardiovascular Diseases; Caregivers; Carps; Case-Control Studies; Catalase; Catalysis; Cats; CD4 Lymphocyte Count; Cell Culture Techniques; Cell Differentiation; Cell Line, Tumor; Cell Membrane; Cell Movement; Cell Proliferation; Cell Survival; Cells, Cultured; Cellulose; Centrosome; Ceratopogonidae; Chickens; Child; China; Cholera Toxin; Choline; Cholinesterases; Chromatography, High Pressure Liquid; Chromatography, Liquid; Chromatography, Micellar Electrokinetic Capillary; Chromatography, Reverse-Phase; Chronic Disease; Cinnamates; Cities; Citrates; Climate Change; Clinical Trials, Phase III as Topic; Coal; Coal Mining; Cohort Studies; Coinfection; Colchicine; Colony Count, Microbial; Colorectal Neoplasms; Coloring Agents; Common Cold; Complement Factor H; Computational Biology; Computer Simulation; Continuous Positive Airway Pressure; Contrast Media; Coordination Complexes; Coronary Artery Bypass; Coronavirus 3C Proteases; Coronavirus Infections; Coronavirus Protease Inhibitors; Corynebacterium glutamicum; Cosmetics; COVID-19; Creatinine; Cross-Sectional Studies; Crotonates; Crystallography, X-Ray; Cues; Culicidae; Culture Media; Curcuma; Cyclopentanes; Cyclopropanes; Cymbopogon; Cystine; Cytochrome P-450 CYP2B6; Cytochrome P-450 CYP2C19; Cytochrome P-450 CYP2C19 Inhibitors; Cytokines; Databases, Genetic; Death; Dendritic Cells; Density Functional Theory; Depsides; Diabetes Mellitus, Type 2; Diamond; Diarylheptanoids; Dibenzofurans; Dibenzofurans, Polychlorinated; Diclofenac; Diet; Dietary Carbohydrates; Dietary Supplements; Diffusion Magnetic Resonance Imaging; Dioxins; Diphenylamine; Disease Outbreaks; Disease Susceptibility; Disulfides; Dithiothreitol; Dizocilpine Maleate; DNA Methylation; DNA-Binding Proteins; DNA, Bacterial; Dogs; Dose-Response Relationship, Drug; Double-Blind Method; Doublecortin Protein; Drosophila melanogaster; Droughts; Drug Carriers; Drug Combinations; Drug Delivery Systems; Drug Liberation; Drug Resistance; Drug Resistance, Bacterial; Drug Resistance, Neoplasm; Drug Screening Assays, Antitumor; Dust; Dynactin Complex; Dysferlin; Echo-Planar Imaging; Echocardiography; Edaravone; Egypt; Elasticity; Electrodes; Electrolytes; Emodin; Emtricitabine; Endometriosis; Endothelium, Vascular; Endotoxins; Energy Metabolism; Energy Transfer; 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Genitalia; Genotype; Glomerulonephritis, IGA; Glottis; Glucocorticoids; Glucose; Glucuronides; Glutathione Transferase; Glycogen Synthase Kinase 3 beta; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Grassland; Guinea Pigs; Half-Life; Head Kidney; Heart Atria; Heart Rate; Heart Septum; HEK293 Cells; Hematopoietic Stem Cells; Hemodynamics; Hep G2 Cells; Hepacivirus; Hepatitis C; Hepatitis C, Chronic; Hepatocytes; Hesperidin; High-Frequency Ventilation; High-Temperature Requirement A Serine Peptidase 1; Hippocampus; Hirudins; History, 20th Century; History, 21st Century; HIV Infections; Homeostasis; Hominidae; Housing, Animal; Humans; Hydrocarbons, Brominated; Hydrogen Bonding; Hydrogen Peroxide; Hydrogen-Ion Concentration; Hydroxybutyrates; Hydroxyl Radical; Hypertension; Hypothyroidism; Image Interpretation, Computer-Assisted; Immunoconjugates; Immunogenic Cell Death; Indoles; Infant, Newborn; Infant, Premature; Infarction, Middle Cerebral Artery; Inflammation; 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Pyridines; Pyrrolidines; Quality of Life; Quantum Dots; Quinoxalines; Quorum Sensing; Radiopharmaceuticals; Rain; Random Allocation; Randomized Controlled Trials as Topic; Rats; Rats, Sprague-Dawley; Rats, Wistar; RAW 264.7 Cells; Reactive Oxygen Species; Receptor, Angiotensin, Type 1; Receptor, PAR-1; Receptors, CXCR4; Receptors, Estrogen; Receptors, Glucocorticoid; Receptors, Interleukin-1; Receptors, Interleukin-17; Receptors, Notch; Recombinant Fusion Proteins; Recombinant Proteins; Reducing Agents; Reflex, Startle; Regional Blood Flow; Regression Analysis; Reperfusion Injury; Reproducibility of Results; Republic of Korea; Respiratory Tract Diseases; Retrospective Studies; Reverse Transcriptase Inhibitors; Rhinitis, Allergic; Risk Assessment; Risk Factors; Rituximab; RNA, Messenger; RNA, Ribosomal, 16S; ROC Curve; Rosmarinic Acid; Running; Ruthenium; Rutin; Sarcolemma; Sarcoma; Sarcopenia; Sarcoplasmic Reticulum; SARS-CoV-2; Scavenger Receptors, Class A; Schools; Seasons; Seeds; Sequence Analysis, DNA; 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Tissue Distribution; Titanium; Toluidines; Tomography, X-Ray Computed; Tooth; Tramadol; Transcription Factor AP-1; Transcription, Genetic; Transfection; Transgender Persons; Translations; Treatment Outcome; Triglycerides; Ubiquinone; Ubiquitin-Specific Proteases; United Kingdom; United States; Up-Regulation; Vascular Stiffness; Veins; Ventricular Remodeling; Viral Load; Virulence Factors; Virus Replication; Vitis; Voice; Voice Quality; Wastewater; Water; Water Pollutants, Chemical; Water-Electrolyte Balance; Weather; Wildfires; Wnt Signaling Pathway; Wound Healing; X-Ray Diffraction; Xenograft Model Antitumor Assays; Young Adult; Zoogloea

In this study we sought to assess the effects of preconditioning with monophosphoryl lipid A on critically ischemic wound margins and on systemic and local hemodynamics and oxygenation during prolonged anesthesia with volatile anesthetics and narcotics. Twenty large white pigs were randomly assigned to receive either monophosphoryl lipid A 35 mug/kg IV or saline 24 h before dissection of a buttock flap. The animals were anesthetized with isoflurane (end-tidal concentration approximately 1.25%) for surgery and subsequent monitoring of hemodynamics and oxygenation both systemically and in the flap tissue for 6 h. Preconditioning resulted in increased cardiac index and oxygen delivery (both P < 0.05) and in decreased central venous pressure and systemic vascular resistance (both P < 0.01). In the preconditioned flap tissue, microcirculatory blood flow (laser Doppler flowmetry) and partial tissue oxygen tension (polarographic microprobes) were up to 2.5-fold higher compared with control (both P < 0.05) and flap necrosis was reduced by 20% on postoperative day 14 (P < 0.05). Our results suggest that preconditioning with a single dose of monophosphoryl lipid A may attenuate ischemia-related wound healing complications, which may be related to an improvement in perfusion and oxygenation of this tissue. Furthermore, preconditioning exerted a systemic cardiovascular stabilization effect during prolonged isoflurane anesthesia.

Topics: Anesthesia, General; Animals; Blood Gas Analysis; Hemodynamics; Ischemic Preconditioning, Myocardial; Laser-Doppler Flowmetry; Lipid A; Myocardial Ischemia; Myocardium; Surgical Flaps; Swine

Monophosphoryl lipid A (MLA), a nontoxic analogue of endotoxin, is a pharmacological agent that is known to have anti-ischemic effects. Mechanisms involved with the cardioprotection are still unclear. A role for inducible nitric oxide synthase (iNOS) was recently proposed. We tested this hypothesis using S-methylisothiourea (SMT), one of the specific pharmacological inhibitors of iNOS, as well as iNOS gene knockout mice.. Adult male ICR or B6,129 mice were pretreated with either MLA 35 or 350 microg/kg IP (MLA35 or MLA350) or vehicle 24 hours before global ischemia/reperfusion, which was carried out in a Langendorff isolated perfused heart model (n=8 to 9 per group). Another group of MLA350 mice received SMT 3 mg/kg IP 30 minutes before heart perfusion. Ventricular contractile function and heart rate were not different between the groups during the preischemia and reperfusion periods (P>0.05). Preischemic basal coronary flow was significantly increased in all MLA350 but not MLA35 mice. Myocardial infarct size was reduced significantly, from 26.9+/-2.9% of risk area in vehicle-treated mice to 13.5+/-2.4% in the MLA350 group (mean+/-SEM, P<0.05). This reduction in infarct size was accompanied by augmented nitrite/nitrate accumulation, from 0.23+/-0. 05 nmol/mg protein in the vehicle group to 0.97+/-0.27 nmol/mg protein in MLA350 mice (P<0.01). Infarct size increased significantly, to 22.2+/-2.8% after treatment with SMT in the MLA350 group. Furthermore, MLA350 failed to reduce infarct size in iNOS knockout mice (25.5+/-3.6%).. These results demonstrate a direct association of infarct size reduction with increased NO production with MLA350. An obligatory role for iNOS in mediating the cardioprotective effect induced by MLA was confirmed with the pharmacological inhibition and gene knockout mice.

Topics: Animals; Body Weight; Cardiotonic Agents; Coronary Circulation; Enzyme Inhibitors; Heart Rate; Hemodynamics; In Vitro Techniques; Isothiuronium; Lipid A; Male; Mice; Mice, Inbred ICR; Mice, Knockout; Myocardial Contraction; Myocardial Infarction; Myocardial Ischemia; Myocardial Reperfusion; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Organ Size; Ventricular Function

Bacterial endotoxin reduces the severity of ventricular arrhythmias which occur when a coronary artery is occluded several hours later. We have now examined in anaesthetised dogs the effects on ischaemia and reperfusion-induced arrhythmias, of a non-toxic derivative component of the endotoxin molecule of the lipid-A (monophosphoryl lipid-A). This was given intravenously, in doses of 10 and 100 microg kg(-1), 24 h prior to coronary artery occlusion. Arrhythmia severity was markedly reduced by monophosphoryl lipid-A. During ischaemia, ventricular premature beats were reduced from 315+/-84 in the vehicle controls to 89+/-60 (with the lower dose of monophosphoryl lipid-A) and 53+/-23 (P<0.05) with the higher dose. The incidence of ventricular tachycardia was reduced from 75% to 25% (P<0.05) and 31% (P<0.05), and the number of episodes of ventricular tachycardia from 13.4+/-4.9 per dog to 1.1+/-1.1 (P<0.05) and 1. 2+/-0.9 (P<0.05) after doses of 10 and 100 microg kg(-1), respectively. The incidence of ventricular fibrillation during occlusion and reperfusion in the control group was 96% (15/16), i.e., only 6% (1/16) dogs survived the combined ischaemia-reperfusion insult. Monophosphoryl lipid-A (100 microg kg(-1)) significantly reduced the incidence of occlusion-induced ventricular fibrillation (from 50% to 7%; P<0.05), and increased survival following reperfusion to 54% (P<0.05). Monophosphoryl lipid-A also significantly reduced ischaemia severity as assessed from ST-segment elevation recorded from epicardial electrodes as well as the degree of inhomogeneity of electrical activation within the ischaemia area. There were no haemodynamic differences prior to coronary occlusion between vehicle controls and monophosphoryl lipid-A-treated dogs. These results demonstrate that monophosphoryl lipid-A reduces arrhythmia severity 24 h after administration. Although the precise mechanisms are still unclear, there is some evidence that nitric oxide and prostanoids (most likely prostacyclin) may be involved because the dual inhibition of nitric oxide synthase and cyclooxygenase enzymes by administration of aminoguanidine and meclofenamate abolished the marked antiarrhythmic protection resulted from monophosphoryl lipid-A treatment 24 h previously.

Topics: Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Arterial Occlusive Diseases; Coronary Vessels; Disease Models, Animal; Dogs; Enzyme Inhibitors; Female; Guanidines; Heart Ventricles; Hemodynamics; Lipid A; Male; Meclofenamic Acid; Myocardial Ischemia; Myocardial Reperfusion Injury; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Prostaglandin-Endoperoxide Synthases; Severity of Illness Index; Tachycardia, Ventricular; Time Factors; Ventricular Fibrillation

A non-toxic derivative of the active lipid A component of the endotoxin molecule (monophosphoryl lipid A) when given to rats in a dose of 5 mg kg(-1) by intraperitoneal injection 24 h prior to anaesthesia and coronary artery occlusion, markedly decreased the severity of ischaemia-reduced ventricular arrhythmias (ventricular fibrillation reduced from 60 to 21%; P < 0.05) and reduced myocardial infarct size (from 35.8 +/- 1.6% of the area at risk to 22.7 +/- 2.0%; P < 0.05). It did not modify blood pressure or heart rate either before or during the period of ischaemia.

Topics: Adjuvants, Immunologic; Animals; Anti-Arrhythmia Agents; Blood Pressure; Heart Rate; Lipid A; Male; Myocardial Infarction; Myocardial Ischemia; Rats; Rats, Sprague-Dawley; Ventricular Fibrillation

We studied whether monophosphoryl lipid A (MLA), an endotoxin derivative, protected the heart from planned ischemia in hypercholesterolemic conscious rabbits. Normal and hypercholesterolemic (8-week exposure to 1.5% cholesterol-enriched diet) conscious rabbits with right ventricular electrode and left ventricular polyethylene catheters were subjected to ventricular overdrive pacing (VOP: 500 beats/min over 10 min = control VOP). The resulting intracavitary ST-segment elevation, increase in left ventricular end-diastolic pressure (LVEDP), and a reduction of ventricular effective refractory period (VERP) were measured. Three days later the animals were given a single intravenous bolus of 10 or 30 microg/kg MLA or its solvent or both, and a second VOP (test VOP) was applied 24 h later. MLA decreased ST elevation and LVEDP increase from 2.1 +/- 0.16 to 1.27 +/- 0.25 and 0.97 +/- 0.13 mV and 14.6 +/- 1.2 to 11.1 +/- 1.0 and 12.4 +/- 1.2 mm Hg in normal animals and from 2.55 +/- 0.14 to 1.31 +/- 0.12 and 0.96 +/- 0.30 mV and from 21.0 +/- 1.6 to 11.7 +/- 1.3 and 12.4 +/- 1.3 mm Hg in atherosclerotic animals after 10- and 30-microg/kg doses, respectively (p < 0.001 for each). VOP-induced VERP reduction was also significantly alleviated by both MLA doses; nevertheless, 30-microg/kg MLA significantly prolonged resting VERP with a slight VERP reduction in response to pacing in both normal and atherosclerotic animals. We conclude that MLA produces a delayed antiischemic effect in both normal and hypercholesterolemic/atherosclerotic conscious rabbits.

Topics: Animals; Arteriosclerosis; Electrophysiology; Heart; Hemodynamics; Hypercholesterolemia; Lipid A; Male; Myocardial Ischemia; Protective Agents; Rabbits

Using the concept that exposing a cell to an adverse environment (stress) results in the stimulation of its endogenous defense system, hearts have been adapted to ischemia by exposing them to diverse stresses. Recently, 24-h pretreatment of monophosphoryl lipid A (MLA), a chemically modified derivative of endotoxin, was found to render the hearts more tolerant to ischemic reperfusion injury. Since nitric oxide has recently been implicated in myocardial preservation and since inducible nitric oxide synthetase (iNOS) was originally characterized in macrophages and shown to be maximally induced by bacterial lipopolysaccharides (endotoxin), we sought to determine whether MLA mediates its cardioprotective effects through the iNOS expression. For this, rats were injected with MLA (300 micrograms/kg) or vehicle (control), and after 24 h the animals were sacrificed and the isolated working hearts were made ischemic for 30 min followed by 30 min of reperfusion. MLA-treated hearts were found to be tolerant to ischemic reperfusion injury as evidenced by improved postischemic ventricular recovery. After 30 min of reperfusion, left ventricular developed pressure (LVDP) and its maximum first derivative (LVmaxdp/dt) were 13.3 +/- 0.3 kPa and 537 +/- 13 kPa/s, respectively, in the MLA-treated group, as compared with 10.2 +/- 0.4 kPa (p < 0.05) and 447 +/- 11 kPa/s (p < 0.05), respectively, for the control group. Aortic flow and coronary flow were 20.1 +/- 1.4 ml/min and 19.1 +/- 0.8 ml/min, respectively, in the MLA group, as compared with 9.5 +/- 0.8 ml/min (p < 0.05) and 15.9 +/- 0.7 ml/min (p < 0.05), respectively, for the untreated group. To examine the induction of the iNOS expression, RNAs were extracted from the control and MLA-treated hearts (after 2, 4, 6, 8, 12 and 24 h of treatment) and Northern blot analysis was performed using specific cDNA probe for iNOS. A single band of approximately 4.6 kb corresponding to iNOS mRNA was detected after 4 h of MLA treatment, while the maximal iNOS expression was found between 6-8 h of MLA treatment. The results of this study demonstrate that MLA induces the expression of iNOS and protects the myocardium from ischemic reperfusion injury.

Topics: Animals; Blotting, Northern; Gene Expression Regulation, Enzymologic; Lipid A; Male; Myocardial Ischemia; Myocardial Reperfusion Injury; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Rats; Rats, Sprague-Dawley; Reperfusion Injury; RNA, Messenger

We examined the in vitro preconditioning effect of non-toxic derivative of endotoxin, monophosphoryl lipid A (MLA) in adult rat cardiac myocytes. Cultured 5-7-day-old myocytes were preconditioned for 4 h by treatment with 200 ng/ml MLA. Twenty h later, cells were subjected to simulated ischemia by incubation in 0.75 mm sodium hydrosulfite, 12 mM KCl, 20 mM dl-lactic acid and 10 mM 2-deoxy-D-glucose (pH 6.5) for 2 h. MLA caused a significant reduction in the levels of LDH from 286+/-8 units/l in controls to 165+/-5 units/l (mean+/-s.e.m.; P<0.0001). Similarly, CK significantly decreased from 104+/-3.1 in controls to 85+/-1.4 U/l (P<0.001). Western blot analysis indicated a significant accumulation of 72 kD heat shock protein in MLA treated as compared to control cells. No changes in 27, 32, and 90 kD heat shock proteins were discernible in the MLA treated group. These data suggest a significant "anti-ischemic" effect of MLA in myocytes that is accompanied by induction of 72 kD heat shock protein.

Topics: Animals; Cardiovascular Agents; Cells, Cultured; Gene Expression Regulation; Heart; Heat-Shock Proteins; HSP72 Heat-Shock Proteins; Ischemic Preconditioning, Myocardial; Lipid A; Myocardial Ischemia; Myocardium; Rats

Topics: Adult; Aged; Aged, 80 and over; Apolipoproteins A; Coronary Angiography; Coronary Disease; Female; Humans; Linear Models; Lipid A; Male; Middle Aged; Myocardial Infarction; Myocardial Ischemia; Prospective Studies

1. Monophosphoryl lipid A (MLA) is a non-pyrogenic derivative of Salmonella lipopolysaccharide. Administration of this agent at high doses to rats and at low doses to dogs was previously shown to confer marked protection against ischaemia-reperfusion 24 h later, although the cellular mechanisms of this delayed protection are obscure. We hypothesized that MLA pretreatment causes the induction of the 70 kDa cytoprotective stress protein HSP70i in the myocardium. If this were the case, protection against ischaemia-reperfusion injury would be observed both in vitro and in vivo. 2. Rabbits were pretreated with MLA 0.035 mg kg-1, i.v. or vehicle solution. For the in vitro study, hearts were isolated 24 h later and Langendorff-perfused with Krebs-Henseleit buffer at 37 degrees C. Global ischaemia was induced for 20 min followed by 120 min reperfusion. Recovery of post-ischaemic left ventricular function and lactate dehydrogenase efflux was similar in MLA and vehicle pretreated hearts and there was no significant difference in the percentage of infarction of the left ventricle determined by triphenyltetrazolium staining (MLA 22.4 +/- 5.2%, vehicle 24.8 +/- 5.1%). 3. When 30 min regional ischaemia and 120 min reperfusion was instituted in pentobarbitone-anaesthetized rabbits 24 h after pretreatment with MLA or vehicle, the percentage infarction within the risk zone was reduced from 42.6 +/- 5.7% in vehicle pretreated animals to 19.6 +/- 4.4% in MLA pretreated animals (P < 0.01). 4. Determination of myocardial HSP70i content by Western blot analysis showed that MLA treatment did not increase HSP70i immunoreactivity. 5. We conclude that MLA at this dose confers protection only against ischaemia-reperfusion injury in vivo and that this protection is not related to induction of HSP70i. Because protection was observed only in vivo it seems possible that the delayed protection conferred by MLA is mediated by effects on humoral or blood-borne factors.

Topics: Adjuvants, Immunologic; Animals; HSP70 Heat-Shock Proteins; In Vitro Techniques; Lipid A; Male; Myocardial Infarction; Myocardial Ischemia; Myocardial Reperfusion Injury; Myocardium; Rabbits

Monophosphoryl lipid A (MLA), a derivative of the minimal substructure of lipopolysaccharide (lipid A) possesses immunomodulatory activity of the parent lipid A yet enjoys reduced toxicity. It has previously been reported that pretreatment with MLA reduces myocardial infarct size and stunning in dogs following ischemia and reperfusion. The aim of this study was to evaluate the ability of monophosphoryl lipid A (MLA) to preserve global cardiac function and peripheral hemodynamics in a rabbit model of prolonged regional ischemia (90 min), and reperfusion (6 h). An evaluation of potential mechanisms by which MLA may preserve cardiac function was also undertaken. Single dose pretreatment with MLA (35 micrograms/kg i.v.) 24 h prior to ischemia resulted in significant improvement in left ventricular developed pressure, dP/dt, rate-pressure product and mean arterial pressure during reperfusion (P < 0.05 v control). Although in this model of prolonged ischemia MLA pretreatment did not reduce infarct size (54.5 +/- 11.4% in control v 63.3 +/- 8.3% in MLA, P = N.S.), evaluation of myocardial adenylate and adenosine catabolite pools at the end of ischemia indicated a preservation of ATP and ADP and a decreased production of downstream adenosine catabolites including inosine, xanthine and uric acid. Adenosine kinase, but not 5'-nucleotidase (5'-NTase) or adenosine deaminase activity determined following reperfusion was 76% and 60% higher (P < 0.05) in non-risk and post-ischemic myocardium of MLA pretreated rabbits compared with controls. Although there was a trend toward lower tissue myeloperoxidase activity in post-ischemic myocardium from treated rabbits, the results were not significantly different from control animals. These results suggest that a 24-h pretreatment with MLA, without further treatment during ischemia or reperfusion was associated with: (1) preservation of global myocardial function during reperfusion; (2) preservation of myocardial high energy adenylates and reduced formation of adenosine catabolites during ischemia; (3) elevated myocardial adenosine kinase activity. Increased recycling of adenosine to phosphorylated nucleotides may result from MLA's affect on adenosine kinase, which could explain the drugs effect on adenylate and adenosine metabolite pools.

Topics: 5'-Nucleotidase; Adenine Nucleotides; Adenosine Deaminase; Adenosine Kinase; Adjuvants, Immunologic; Analysis of Variance; Animals; Blood Pressure; Carbohydrate Sequence; Coronary Vessels; Energy Metabolism; Female; Heart; Heart Rate; Hemodynamics; Lipid A; Molecular Sequence Data; Myocardial Infarction; Myocardial Ischemia; Myocardial Reperfusion; Myocardium; Peroxidase; Purines; Rabbits; Reference Values; Ventricular Function, Left

The purpose of this study was to evaluate the protective effect of a new endotoxin analogue, monophosphoryl lipid A (MLA) in a rabbit model of myocardial ischemia/reperfusion and to show if this protection was mediated via synthesis of 70 kDa heat shock protein (HSP 70). Three groups of New Zealand White rabbits underwent 30 min coronary occlusion, followed by 4 hours reperfusion. First group of rabbits (n = 6) were treated with 0.35 ml vehicle (40% propylene glycol, 10% ethanol in water). The second and third group of rabbits (n = 6-8) were treated with MLA (35 micrograms/kg, i.v.) 12 and 24 hours prior to ischemia and reperfusion. MLA treatment either 12 or 24 h prior to ischemia/reperfusion demonstrated significantly reduced infarct size (12.5 +/- 1.7 and 14.7 +/- 2.1% for 12 and 24 h) when compared with vehicle control (40.4 +/- 8.6%, mean +/- S.E.M, p < 0.05). No significant differences in the infarct size was observed between the 12 and 24 h MLA treated groups. The area at risk was not significantly different between the three groups. Baseline values of heart rate, systolic and diastolic blood pressure were not significantly different between the control and MLA treated groups. However, the systolic as well as diastolic blood pressure during reperfusion were significantly lower in rabbits treated with MLA. Western blot analysis of the protein extracts of the hearts (n = 2/group) demonstrated no increase in the expression of the inducible form of HSP 70 following treatment with MLA. We conclude that MLA has significant anti-infarct effect in rabbit which is not mediated by the cardioprotective protein HSP 70. The anti-infarct effect of this drug is superior to the reported protective effects of delayed ischemic or heat stress preconditioning. We hypothesize that the pharmacologic preconditioning afforded by MLA is accomplished via a unique pathway that bypasses the usual intracellular signaling pathways which lead to the myocardial protection with the expression of heat shock proteins.

Topics: Animals; Blood Pressure; Blotting, Western; Heart Rate; HSP70 Heat-Shock Proteins; Lipid A; Male; Molecular Structure; Myocardial Infarction; Myocardial Ischemia; Myocardium; Rabbits; Reperfusion; Signal Transduction

We wished to determine if the previously observed cardioprotective effects of monophosphoryl lipid A (MLA, 65 micrograms/kg intravenously, i.v.), an endotoxin derivative, were time related and mediated by an enhancement of antioxidant defense mechanisms, i.e., myocardial catalase and superoxide dismutase (SOD) activities and neutrophil infiltration as assessed by myeloperoxidase (MPO) activity. We also wished to study the effect of pretreatment with MLA on vascular endothelial and smooth muscle function in vivo and in vitro. Barbital-anesthetized dogs were subjected to 60-min left circumflex coronary artery (LCX) occlusion followed by 5-h reperfusion. Myocardial catalase, SOD, and MPO activities were measured at the end of 5-h reperfusion. Pretreatment with MLA 24 h before ischemia produced a significant reduction in myocardial infarct size as measured by triphenyltetrazolium staining (15.3 +/- 4.4 vs. 30.9 +/- 5.2% in controls, p < 0.05), but 1-h pretreatment with MLA had no protective effect. MLA pretreatment for 24 h resulted in marked reduction (p < 0.05) in MPO activity in the border zone surrounding the infarct. Although a trend indicated an increase in catalase activity in the 24-h pretreatment group, no significant changes were observed in either catalase or SOD activities among the three groups. The cardioprotection produced by MLA was independent of differences in collateral blood flow to the ischemic region assessed by radioactive microsphere technique, systemic hemodynamics, myocardial oxygen demand, and ischemic bed size. Responses of the LCX bed to intracoronary acetylcholine (ACh) or nitroglycerin (NTG) in vivo and responses of isolated femoral artery rings to the endothelium-dependent vasodilators, ACh, A23187, bradykinin, or the nonendothelium-dependent vasodilator, sodium nitroprusside (SNP) in vitro were significantly decreased in the MLA 1-h pretreatment group but not in the 24-h pretreatment group. Incubation of the femoral artery rings from the MLA 1-h pretreatment group with 3 mM L-arginine for 1 h reversed the decreased endothelium-dependent responses to ACh and A23187, but not those to bradykinin. These results indicate that (a) the MLA-induced myocardial infarct size reduction was pronounced when MLA was administered for 24 h but was not evident at 1-h pretreatment; (b) a decrease in neutrophil infiltration into the site of ongoing tissue damage might be partially responsible for the protection; (c) vascular endothelial and/or sm

Topics: Animals; Blood Gas Analysis; Body Temperature; Catalase; Coronary Circulation; Dogs; Endothelium, Vascular; Female; Heart; Hemodynamics; Lipid A; Male; Muscle, Smooth, Vascular; Myocardial Ischemia; Myocardial Reperfusion Injury; Myocardium; Peroxidase; Random Allocation; Superoxide Dismutase; Vasodilator Agents