title: Doxorubicin dose for congestive heart failure modeling and the use of general ultrasound equipment for evaluation in rats. Longitudinal in vivo study.
abstract: BACKGROUND
  For the evaluation of the congestive heart failure (CHF) in rat models, the use of special equipment for echocardiography for dynamic evaluation is suggested. The optimal doxorubicin dose for CHF induction has still not been established.
  
  
  OBJECTIVE
  The aims of our study was to find a reliable doxorubicin CHF rat model using a general ultrasound (US) equipment for in vivo ultrasound examination of the systemic circulation, to establish the optimal doxorubicin dose, and to assess the feasibility of US guided administration of the drug.
  
  
  METHODS
  Sixty Wistar rats, weighing 180-200 g were assigned to 3 groups (n=20 in each): group A - 4 time intraperitoneal doxorubicin "Sigma"administration, cumulative dose 2.49 mg/animal or 12.45 mg/kg; group B and 5 time doxorubicin administration, cumulative dose 3.03 mg/animal or 15.15 mg/kg; and group C- controls (injected same volume of saline). Dynamic US using linear 12 MHz transducer was used to establish the CHF modifications. Two rats with CHF were injected under US guidance in the pleural cavity with 0.06 ml cardiotropic drug levosimendan and two rats in the pericardial cavity.
  
  
  RESULTS
  We established the optimal cumulative doxorubicin dose for CHF induction at 12.45 mg/kg. At a higher dose, more than 40% of animals died. A lower dose did not induce significant clinical and US CHF criteria. Congestion (followed by weight gain) led to lower animal mortality. Preliminary results indicate a similar positive cardioprotective effect of drug injection into pericardial and pleural cavities under US guidance, demonstrating that this technique is useful for drug administration.
  
  
  CONCLUSIONS
  US is an effective modality for in vivo monitoring of the rat organs for the study of cardiovascular function or for drug administration under US guidance. Suggested model (optimal dose of doxorubicin for simulation of CHF of 2.5 mg/animal, a cumulative dose of 12.45 mg/kg in 4 injections every 3 days) can be used for research purposes.
authors.affiliation: Zabolotny Institute of Microbiology and Virology, National Academy of Sciences of Ukraine, Kyiv, Ukraine. rostbubnov@gmail.com
authors.forename: Mykola
authors.initials: M
authors.lastname: Spivak
authors.forename: Rostyslav
authors.initials: R
authors.lastname: Bubnov
authors.forename: Ilya
authors.initials: I
authors.lastname: Yemets
authors.forename: Liudmyla
authors.initials: L
authors.lastname: Lazarenko
authors.forename: Natalia
authors.initials: N
authors.lastname: Timoshok
authors.forename: Anna
authors.initials: A
authors.lastname: Vorobieva
authors.forename: Sergii
authors.initials: S
authors.lastname: Mohnatyy
authors.forename: Zoia
authors.initials: Z
authors.lastname: Ulberg
authors.forename: Liudmyla
authors.initials: L
authors.lastname: Reznichenko
authors.forename: Tamara
authors.initials: T
authors.lastname: Grusina
authors.forename: Volodymyr
authors.initials: V
authors.lastname: Zhovnir
authors.forename: Nadia
authors.initials: N
authors.lastname: Zholobak
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage*; D004452:Echocardiography / Q000295:instrumentation* / Q000379:methods*; D004867:Equipment Design; D019544:Equipment Failure Analysis; D005260:Female; D006333:Heart Failure / Q000139:chemically induced* / Q000000981:diagnostic imaging*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D004317:Doxorubicin