DOCA‐salts induce heart failure in the guinea pig

AbstractHeart failure (HF) is a common clinical problem confronting physicians and is often the final manifestation of many cardiovascular disorders. Despite recent advances in the pharmacological management of HF, it remains a highly lethal and disabling disorder. A number of animal models have been developed to study both the pathophysiology of HF and new therapeutic approaches to this complex syndrome. Only through an improved understanding of the basic biology of the early stages of the syndrome can HF be prevented or at least anticipated. With this in view, we have developed an easily realisable and inexpensive model in the guinea pig, which presents numerous structural, metabolic and biochemical similarities compared with the human heart. Thirty guinea pigs, aged 5 weeks and weighing 300 g were used. After anaesthesia, left nephrectomy was performed. After 1 week the guinea pigs were divided into: (a) control group (n ‐ 15), which received an injection of vehicle as well as tap water for 10 weeks; (b) DOCA‐salts group (n ‐ 15), where the animals were treated with an IM injection of 10 mg DOCA 5 days a week for 10 weeks and with drinking water containing 9 g/l−1 NaCl and 2 g/l−1 KCl. Our results demonstrate that the administration of DOCA‐salts to guinea pigs for 10 weeks caused a significant increase in blood pressure (BP + 30%) associated with left ventricular hypertrophy (LVH), evaluated by LV weight (+37%), LV wall (+36%), by the ratio LV weight/Body weight (+23%) and by an increase in LV volume (+51%). Concerning HF, the latter was clinically evident through an increase in body weight, heart rate and dyspnoea. Indeed, guinea pigs presented pleural and/or pericardial effusion often associated with ascite. This model, which combines pressure and volume overload, results in a slow evolution towards HF. This allows a better understanding of the mechanisms in early LV remodelling which has the potential to develop into HF. Some recent studies have emphasised the value of using guinea pigs. The guinea pig heart muscle presents two major regulatory mechanisms of contractility that are closer to those found in humans, the isomyosin pattern which is predominantly V3 and the phenomenon of Ca2+‐induced Ca2+‐release from the sarcoplasmic reticulum. The DOCA‐salts model in the guinea pig is an easy surgical procedure with high post‐operative survival, which causes an increase in arterial BP, LVH associated with HF. This model is a useful tool for studying some of the basic mechanisms of cardiovascular diseases.