16 Jan Statins improve standard treatment with preserved systolic function in a rat heart failure model
Studies in the US have reported that 40% of incident congestive heart failure (CHF) cases and 50% to 60% of prevalent CHF cases occur in the setting of preserved systolic function (with an ejection fraction above 50%). This condition, termed “diastolic heart failure”(DHF), is a major health problem in the U.S., particularly among the elderly. The mortality and morbidity rates of patients with DHF are high, and similar to those of patients with Heart failure (HF) and systolic dysfunction. Unfortunately, no treatment has yet been shown to convincingly improve survival in patients with DHF.
Currently, symptoms are controlled, the heart rate is kept under check and fluid retention is reduced but the disease isn’t treated. Combined therapies that target individual symptoms are the current optimal therapeutic strategy. However, new drugs which target more or different systems are required. Researchers from Spain, focussed of statins as a treatment. Already well-established lipid-lowering therapies that reduce morbidity and mortality in patients with coronary artery disease, the potential benefit of statins in establishes HF is still unclear. Several studies in experimental models and patients have suggested that statins may directly improve left ventricular (LV) relaxation and function by reducing LV hypertrophy and fibrosis, and increasing arterial compliance. They also have known anti-inflammatory and antioxidant actions, as well as a protective effect against endothelial dysfunction.
The researchers looked into the early use of rosuvastatin in combination with a standard HF therapy in a genetic rat model of hypertensive heart failure (SHHF), a solution which would reflect clinical practice more closely. SHHF rats are characterized by a compensated stage in which animals are hypertensive as early as 12 weeks of age. This is followed by myocardial hypertrophy with cardiac relaxation abnormalities at 9 months of age. At around 15–18 months of age, animals begin to transition to a decompensated state with many hallmark features of overt HF.
Two-month-old SHHF rats were randomly given rosuvastatin; quinapril + torasemide + carvedilol (considered as standard HF therapy); standard HF therapy + rosuvastatin; or nothing at all. As expected, the standard anti-hypertensive HF therapy given to the rats for a period of 17 months improved LV chamber dilatation, cardiac hypertrophy, fibrosis, and inflammation compared with non-treated SHHF rats. Rosuvastatin alone prevented LV dilatation and cardiac inflammation similar to standard therapy, despite being unable to normalize blood pressure or influence cardiac hypertrophy.
But most importantly, the combination of both rosuvastatin to the standard HF therapy, had a cumulative effect and further prevented LV dilatation, preserved cardiac function, and normalized inflammation. Significant additional improvements in HF and cardiac remodelling were visible. These beneficial effects were independent of BP and plasma lipid changes, and seem to be due, at least in part, to decreased myocardial inflammation.
European Journal of Heart Failure (2010) 12, 903–912 doi:10.1093/eurjhf/hfq101
Syncrosome, a scientific preclinical CRO based in France, also uses a rat with Chronic coronary ligature to model Heart failure for efficacy testing. They monitor, Doppler echocardiography, Coronary artery ligation, reperfusion, blood pressure, heart rate, planimetry, histology and morphological and functional biomarkers. By combining all these parameters, they can most reliably test for appropriate reaction.
Key words: preclinical CRO, preclinical study, animal model, animal research, myocardial, heart failure, infarction, echocardiography, heart, rat model, good model, ventricle, myocardial infarction, Congestive heart failure, systolic function, diastolic heart failure