Resumo (PT):
Pulmonary hypertension (PH) is characterized by structural changes of the pulmonary
vessels as well as right ventricular (RV) hypertrophy. The reversibility of
pulmonary vascular remodeling is possible only at paediatric ages. The monocrotaline
(MCT)-induced PH model is well defined for adult animals and mimics human
PH. The aim of the study is to establish neonatal and infantile HTP models
by MCT administration and to evaluate morphometric and haemodynamic parameters.
Protocol 1. Wistar rats 3- and 8-day-old were injected with different doses of MCT:
a) 60 mg/kg, n=35; b) 50mg/kg, n=31; c) 30mg/kg, n=40. Protocol 2. Wistar rats
with 3 (neonatal) or 8-day-old (infantile) randomly received a subcutaneous injection
of MCT 30mg/kg (MCT-Neo, n=10; MCT-Inf, n=10) or an equal volume of
vehicle (Ctrl-Neo, n=10; Ctrl-Inf, n=10). At day 21 after injection, RV and left ventricular
(LV) peak systolic (RVPmax) and end-diastolic (RVEDP) pressures, peak
rates of ventricular pressure rise (dP/dtmax) and relaxation rate (Tau RV) were
recorded. At the end, heart and lungs were excised and weighted.
Protocol 1. Survival rates at day 21: MCT60=0%; MCT50=0%; MCT30=85%. Protocol
2. Results expressed as means±SE and summarized in table. P<0.05: a vs
Ctrl.
Protocol 2 - Results
Ctrl-Neo MCT-Neo Ctrl-Inf MCT-Inf
Body Weight, g 46±1 47±2 80±1 58±3 a
RV/LV g/g 0.29±0.02 0.41±0.03 a 0.28±0.02 0.40±0.02 a
Lung, g 0.404±0.02 0.478±0.02 0.680±0.28 0.656±0.83
RVPmax, mmHg 18.3±1.9 41.9±1.3 a 19.6±2.8 37.1±4.7 a
RVEDP, mmHg 1.1±0.4 2.3±0.5 a 0.4±0.7 2.9±1.4 a
dP/dtmax RV, mmHg/s 657±157 1094±106 a 663±74 1210±258 a
Tau RV, ms 20±1 31±4 a 21±5 33±9 a
We characterized haemodynamics of healthy and PH Wistar rats during the childhood
period. We established the survival until 3 weeks after the injection of MCT
30mg/kg. We documented, in both neonatal and infantile groups, prominent RV
hypertrophy, pulmonary hypertension and diastolic dysfunction. No differences
were found in LV data. This model will allow to study the similarities and differences
with the adult model and to test the effects of new drugs in neonatal and
infantile PH.
Language:
English
Type (Professor's evaluation):
Scientific
Notes:
XVth World Congress of Cardiology, published in journal, European Heart Journal. 2006; Vol.27(Suppl.1):618-618.