Left ventricular response to sustained volume overload from chronic aortic valve regurgitation in rats

Abstract

Objectives: Aortic regurgitation (AR) induces left ventricular (LV) eccentric hypertrophy in response to chronic volume overload. Patients suffering from this disease often remain asymptomatic for decades before progressive LV dysfunction develops silently. Because of this slow evolution, large clinical trials with long-term follow-up on subjects with chronic AR are hard to perform. To overcome this problem, animal models have been developed in the past but results were very heterogeneous. Methods: Helped by echocardiography, we refined a known technique to induce homogenous degrees of severe AR in Wistar-Kyoto rats. The effects on LV function without treatment and with nifedipine (25 mg/kg daily) (a drug currently recommended in humans with chronic AR) were evaluated by echocardiography. Results: Over 6 months, nontreated animals developed progressive LV dilatation and eccentric hypertrophy, characteristic of chronic LV volume overload. The animals also developed progressive LV systolic dysfunction, mimicking closely the evolution of the disease in humans. Abnormal filling parameters were also detected in the majority of animals. Systolic and diastolic abnormalities were prevented but only partially in the group treated with nifedipine. Conclusion: This model can be used to study chronic AR and LV dysfunction associated with the disease. Nifedipine seems to protect the LV against chronic volume overload but only partially. Treatment strategies currently used in humans deserve further investigation.