cardiactoxicology-theuniversityofnorthcarolinaat心臟毒理學-北卡羅來那大學(編輯修改稿)
2025-02-14 23:54 本頁面
【文章內(nèi)容簡介】 myocardial necrosis Toxicants That Alter Cell Membrane Function ? Alter cell membrane control of ion movement and affect cardiac contraction – Toxicants that bind to phospholipids (., gossypol) ? effect potassium transport ? hyperkalemia ? arrhythmias – Toxicants that selectively block sodium channels ? tetrodotoxin, saxitoxin ? decreased intracellular Na+ ? depression of normal pacemaker function and conduction ? arrhythmias Toxicants That Directly Damage Myocardium ? Damage the pumping effectiveness by reducing the number of active myocytes – Toxicants that cause oxidative damage and lipid peroxidation (., doxorubicin, ethanol) ? redox cycling of doxorubicin ? semiquinone and superoxide radicals ? ethanol metabolism ? lipid peroxidation of myocytes ? results in cell swelling, altered Ca2+ homeostasis, and irreversible myocyte injury Toxicants That Directly Damage Myocardium ? Damage the pumping effectiveness by reducing the number of active myocytes – Toxicants that cause sarcolemmal injury and calcium alterations (., catecholamines) ? endogenous: epinephrine and norepinephrine ? exogenous: isoproterenol ( toxicity than above) ? sarcolemmal damage through lipid peroxidation ? increased calcium uptake ? impaired mitochondrial function and activation of neutral proteases and phospholipases ? myocyte dysfunction and toxicity Cardiovascular changes following chronic rodent exposure to dioxinlike pounds Reference: Jokinen MP, Walker NJ, Brix AE, Sells DM , Haseman JK, Nyska A (2022). Cardiovascular Pathology in Female SpragueDawley Rats Following Chronic Treatment with Dioxinlike Compounds. Cardiovascular Toxicology. 。 3(4): 299310 Cardiomyopathy ? Myocardial fiber degeneration/necrosis, inflammation, fibrosis ? Common spontaneous degenerative change of myocardium in old rats – Cause unknown but is affected by diet and stress Incidences of Cardiomyopathy ? TCDD ? PCB126 Dose (ng/kg) 0 3 10 22 46 100 100 stop 10 12 22 25 32 36 22 Dose (ng/kg) 0 30 100 175 300 550 1000 1000 stop 9 16 17 16 24 28 32 15 Normal heart Cardiomyopathy Cardiac Toxicity observed in 90days exposure to Bis(2chloroethoxy)methane in rats and mice Bis (2chloroethoxy)methane (CEM) is a synthetic anic pound used as the starting pound to produce polysulfide elastomers used extensively in a variety of sealant applications. Histopathologic definitions of cardiac lesions Myocyte vacuolization Widespread accumulation of multiple, round, variably sized, primarily small, and clear vacuoles, located within the myocyte sarcoplasm Vacuoles, often similar in appearance, present in the interstitium are interpreted as a background change Histopathologic definitions of cardiac lesions (Cont.) Myocyte necrosis Small areas containing fragmented, angular, brightly eosinophilic myofibers with dark, shrunken nuclei Atrial thrombosis A mature, antemortem blood clot present within the lumen of the atrium, consisting of alternating areas of fibrin and
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