DOCA‐salts induce heart failure in the guinea pig

Abstract

Ž .Heart 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 Ž . Ž . nephrectomy was performed. After 1 week the guinea pigs were divided into: a control group n s 15 , which received an Ž . Ž . injection of vehicle as well as tap water for 10 weeks; b DOCA-salts group n s 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 grl y1 NaCl and 2 grl y1 KCl. Our results demonstrate that the administration of DOCA-salts to guinea pigs for 10 weeks caused a significant increase in Ž . Ž . Ž . blood pressure BP q 30% associated with left ventricular hypertrophy LVH , evaluated by LV weight q37% , LV wall Ž . Ž . Ž . q36% , by the ratio LV weightrBody weight q23% and by an increase in LV volume q51% . Concerning HF, the latter was clinically evident through an increase in body weight, heart rate and dyspnoea. Indeed, guinea pigs presented pleural andror 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 V and the phenomenon of Ca 2q -induced Ca 2q -release from the sarcoplasmic reticulum. The 3 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. ᮊ

Kallikrein gene transfer reduces renal fibrosis, hypertrophy, and proliferation in DOCA-salt hypertensive rats

“…DOCA-salt treatment often triggers a malignant hypertension that gradually leads to damage of the kidney, heart, and vasculatures (18,24,34,36). Glomerular sclerosis, tubular fibrosis, and cardiac hypertrophy and fibrosis are commonly observed in DOCA-salt-treated animals, along with activation of renal transforming growth factor (TGF)-␤1 expression and downregulation of endothelial nitric oxide synthase levels in the heart, kidney, and blood vessels (19,37).…”

Differences in Mechanical, Electrical and Calcium Transient Performance of the Isolated Right Atrial and Ventricular Myocardium of Guinea Pigs at Different Preloads (Lengths)

“…With regard to the present work, it should be emphasised that there is a lack of data studying the effects of sequential changes in the myocardial length of the different heart chambers of different animals, including the guinea pig, on electromechanical coupling, with the exception of our work on the rat heart [34]. The present study was performed on guinea pig myocardial preparations because their myocardium differs from the rat myocardium in electromechanical coupling and is similar to the human myocardium [21,35,36].…”

“…2023, 24, x FOR PEER REVIEW 3 of 17 the rat heart [34]. The present study was performed on guinea pig myocardial preparations because their myocardium differs from the rat myocardium in electromechanical coupling and is similar to the human myocardium [21,35,36].…”

A case of infectious pericardial effusion and tamponade in a guinea pig (Cavia porcellus) associated with a multiresistant staphylococcus

“…Two other reported cases in guinea pigs showed a moderate enlargement of the left atrium (Dzyban and others 2001) for one and a moderate right‐sided ventricular and atrial dilation for the other (Perry and others 2012). Guinea pigs models of human heart failure show that systemic hypertension induces left ventricular remodelling, leading to heart failure characterised by left ventricular hypertrophy, PE, pleural effusion and ascites (Tiritilli, 2011). A retrospective study over a two‐year time period (2010–2012) at Advetia specialty practice in a population of 810 guinea pigs revealed 18 (2.22 per cent) guinea pig with cardiomegaly.…”