Cardiovascular in vivo modeling
Comparative Biosciences, Inc. has extensive experience in cardiovascular modeling, in particular, the LAD Model in rats, balloon angioplasty in rats and rabbits, and stent preclinical studies, in both the in life phase and the histopathology to support these studies.
Monocrotaline-induced Pulmonary Hypertension in Rats
A single dose of monocrotaline administered to rats will induce pulmonary hypertension by causing smooth muscle hypertrophy of the walls of arteries in the lungs. This validated model is useful to assess the activity of test articles that may have activity in this 
therapeutic area. The graph presents pulmonary artery pressures from normal and monocrotaline treated rats demonstrating increased pressure 21 days post injection.
A typical design includes four groups with ten rats per group induced by a single dose of monocrotaline. In life assessments would include clinical observations, body weights and food consumption with sacrifice at day 21 or 35. Terminal assessments would include:
- Pulmonary artery and right ventricular blood pressure measurements via thoracotomy
- Heart and lung weights
- Weight of right ventricle
- Precision cutting of the heart using a heart mold to obtain uniform sections for histopathologic assessment and histomorphometry
- Histomorphometric assessment of ventricle thickness
- Histopathologic assessment of vascular changes in lungs, including histomorphometric assessment of vessel wall thickness
- Special stains and immunohistochemistry
- Complete report with photomicrographs, morphometry, and statistics
Myocardial ischemia and reperfusion (LAD in rats)
In this model, the LAD is ligated either permanently or for up to 1 hr followed by re-perfusion. Rats are recovered and a treatment regime is instituted. At the end of the in life phase, the size of the infarction is assessed by a variety of means such as dye exclusion, histopathology, special stains, immunohistochemistry, and histomorphometry. A typical study has at least 10 animals per group including a vehicle, two-three test article doses, and possibly a positive control.
Balloon angioplasty and restenosis in rats and rabbits
In this model, selected vessels are denuded. Over several weeks, neointimal proliferation (restenosis injury) occurs. Treatment is administered. At the end of the in life phase, the size and character of the restenosis injury is assessed by a variety of means such as histopathology, special stains, immunohistochemistry, and histomorphometry. A typical study has at least 8 animals per group including a vehicle, sham, two-three test article doses, and a positive control.