Heart failure

CARDIOVASCULAR SYSTEM

Porsolt has an extensive portfolio of cardiovascular procedures, ranging from standard cardiovascular telemetry studies for safety evaluation, to pathophysiological models for specific therapeutic areas. Porsolt also possesses considerable expertise with in vitro models, providing clients with a comprehensive assessment of all aspects of cardiovascular function.

Heart failure

Congestive Heart Failure

The cardiomyopathic Syrian hamster (Bio TO-2 dilated strain) is a genetic model of congestive heart failure. These animals progressively develop an alteration of cardiac function leading to decreased arterial blood pressure and musculo-cutaneous blood flow associated with a complex process of cardiac remodeling including atrial hypertrophy, left ventricle dilation, wall thinning and greater collagen density (Goineau & al. Can. J. Physiol. Pharmacol. 2001).
Our procedure allows for the evaluation of new therapies with the potential to prevent (or to slow) the natural progression of the disease (i.e. by starting treatment prior to the development of pathology) or to reverse the pathophysiological syndrome (i.e. by starting treatment after ventricular dysfunction and cardiac remodeling has become established).
The pharmacological effects of new therapeutic strategies can be evaluated on cardiac and systemic hemodynamics, morphometry (body and target organ weight), cardiac remodeling (left ventricle collagen density, cavity area and wall thickness) and survival.

Cardiac and systemic hemodynamics

Cardiac and systemic hemodynamics

Above are shown examples of results obtained with enalapril, an inhibitor of angiotensin I converting enzyme, administered orally at 20 mg/kg/day from 120 days of age. The data in these graphs are from measurements taken at 250 days of age, i.e. after 130 days of treatment.
Left ventricle and systemic blood pressures and cardiac output are measured in anesthetized animals.
These data demonstrate that enalapril improves cardiac and systemic hemodynamics in this model.

Left ventricle remodeling

Histomorphometric analyses are performed using a computer-assisted analysis of left ventricle slices stained with Sirius red.

This analysis shows that enalapril exerts beneficial effects on cardiac remodeling.

Examples of left ventricle slices stained with Sirius red for measurement of collagen density

Survival curves

Chronic administration of enalapril from 120 days of age increases survival in cardiomyopathic hamsters.

Median increase in survival time: +30 days, p < 0.05.

The data presented here demonstrate the translational value of this model for studying congestive heart failure in that the cardiomyopathic hamster demonstrates all of the hallmarks of human congestive heart failure and the clinically effective agent enalapril can successfully be used to attenuate those pathophysiological changes and to significantly improve survival.