ABSTRACT
The correlation among clinicopathological parameters of myocardial damage was investigated in rats administered a single subcutaneous dose of isoproterenol at 0 (saline), 0.04, 0.4 and 4 mg/kg. Total lactate dehydrogenase (LDH), creatine kinase (CK), and their isoenzymes (LDH-1, LDH-2 and CK-MB), as well as troponin I and tropinin T, were measured 4 h after the administration of the drug. Troponin I was determined by a chemiluminescence method using Bayer Centaur and DPC Immulyze, as well as by ELISA. Troponin T was assayed semi-quantitatively using Trop T Sensitive. A high correlation was found among LDH isoenzymes, troponin I (Centaur) and troponin T. The present result provides a baseline for interpreting changes in the different parameters of myocardial damage assayed by different methods in toxicity studies.
Subject(s)
Creatine Kinase/blood , Heart/drug effects , Isoproterenol/toxicity , L-Lactate Dehydrogenase/blood , Myocardium/pathology , Toxicity Tests/methods , Troponin I/blood , Troponin T/blood , Animals , Biomarkers/blood , Injections, Subcutaneous , Isoenzymes/blood , Isoproterenol/administration & dosage , Male , Rats , Rats, Inbred StrainsABSTRACT
A battery of simple tests for profiling abnormalities of vitamin K-dependent coagulation factors encountered in drug-toxicity studies was verified in rats treated with warfarin (3 and 10 mg/kg, p.o). The thrombotest, or hepaplastin-test, is useful as a follow-up test after routine screening tests for coagulation abnormalities based on PT and APTT, to rule out other coagulation-factor abnormalities. Measurement of coagulation factor activities (factors II, VII, IX and X) using factor-deficient human plasmas provides direct evidence of decreased activities of vitamin K-dependent factors. Furthermore, Echis carinatus venom coagulation time, together with factor II activity, allows us to confirm the generation of PIVKA-II.
Subject(s)
Biomarkers/blood , Blood Coagulation Factors/analysis , Blood Coagulation Tests/methods , Protein Precursors/blood , Vitamin K , Animals , Blood Coagulation Disorders/blood , Blood Coagulation Disorders/chemically induced , Male , Prothrombin , Rats , Rats, Inbred Strains , Toxicity Tests , WarfarinABSTRACT
The possible mechanisms for shortening prothrombin time (PT) and activated partial thromboplastin time (APTT) were investigated using citrated plasma from rats and dogs in vitro, especially focusing on increased fibrinogen concentrations. When purified canine fibrinogen was added to citrated canine plasma at final concentrations of 2, 4 and 8 mg/mL, PT and APTT were significantly shortened. The increased concentrations of clottable fibrinogen in the test system were confirmed by markedly shortened thrombin time (TT). In citrated rat plasma, while purified rat fibrinogen had no effect on PT or APTT at final concentrations of 2, 4 and 8 mg/mL, it did shorten TT. These results suggest that an increased concentration of fibrinogen is a possible mechanism to shorten PT and APTT in dogs, but not in rats.
