Recirculating, retrograde heart perfusion according to the Langendorff method for evaluation of MTG--methyl-2-tetradecylglycidate, McNeil 3716--cardiomyopathy.
Recirculating, retrograde heart perfusion according to the Langendorff method was used in an attempt to further elucidate the cardiotoxicity of methyl-2-tetradecylglycidate (McNeil 3716, MTG) and the eccentric hypertrophy elicited by the compound. In subchronic experiments female rats were exposed to MTG 2 x 10 mg/kg and 2 x 25 mg/kg per day for 4 weeks. At various times hearts were perfused ex vivo for up to 2 hr with either 5 mmolar glucose or 0.5 mmolar palmitate as substrate. Substrate uptake (glucose or palmitate) and enzyme release (LDH-lactic dehydrogenase or CPK-creatine-phosphate kinase) were assessed during perfusion. Biochemical analysis (ATP, ADP, AMP, c-AMP, CP, creatine, pyruvate, lactate, glucose-6-phosphate, glycogen, phospholipids, triglycerides and non-esterified fatty acids) were done in hearts before (drug effect) and after perfusion (stress of perfusion). Besides changes in energy metabolism and high-energy phosphate production, as observed in previous experiments (Bachmann et al. 1984) massive changes were seen in energy reserves in heart tissue (ATP, CP, glycogen, phospholipids and triglycerides). As expected, MTG led to significant increases also in non-esterified fatty acids content in hearts.
Bachmann
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Institute of Toxicology, Swiss Federal Institute of Technology, Schwerzenbach, Schweiz.
Weber
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D000227:Adenine Nucleotides / Q000378:metabolism; D000818:Animals; D006332:Cardiomegaly / Q000139:chemically induced* / Q000201:enzymology / Q000378:metabolism; D003402:Creatine Kinase / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects; D004852:Epoxy Compounds / Q000633:toxicity*; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005260:Female; D005947:Glucose / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000633:toxicity*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D050356:Lipid Metabolism; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism; D010169:Palmitic Acids / Q000378:metabolism; D010477:Perfusion; D010725:Phosphocreatine / Q000378:metabolism; D011422:Propionates / Q000633:toxicity*; D051381:Rats; D014280:Triglycerides / Q000378:metabolism
D000227:Adenine Nucleotides; D004852:Epoxy Compounds; D005230:Fatty Acids, Nonesterified; D007004:Hypoglycemic Agents; D010169:Palmitic Acids; D011422:Propionates; D014280:Triglycerides; D010725:Phosphocreatine; D006003:Glycogen; D007770:L-Lactate Dehydrogenase; D003402:Creatine Kinase; D005947:Glucose; C017522:methyl 2-tetradecylglycidate