Immune-inflammatory concept of the pathogenesis of chronic heart failure in dogs with dilated cardiomyopathy

Abstract

Background: Dilated cardiomyopathy is common in dogs. This form of cardiomyopathy is the main cause of death due to heart disease in dogs. Death can occur suddenly in clinically normal animals as a result of the progression of congestive heart failure (CHF). The pathogenesis of heart failure syndrome in dogs with dilated cardiomyopathy involves activation of the neurohumoral system and immune-mediated inflammation, which leads to further progression of the condition. Heart failure syndrome in dogs with dilated cardiomyopathy is caused by the progressive loss of cardiomyocytes, apoptosis, remodeling of the left ventricle, systolic and diastolic dysfunction, arrhythmias, reduced cerebral blood flow, the involvement of other key internal organs, and intestinal dysbiosis. Aim: This study aimed to determine the immunological and inflammatory mechanisms surrounding the development of heart failure syndrome in dogs with dilated cardiomyopathy. Materials and Methods: The subjects of this study were dogs with a dilated form of cardiomyopathy (n=159), complicated by various functional classes of heart failure syndrome. Evaluation of myocardial remodeling, systolic function, and systemic hemodynamics was performed using EMP-860 Vet and PU-2200V ultrasound scanners according to the standard technique. Electrocardiography was performed with all dogs in right lateral recumbency using the EK1T-04 Midas electrocardiograph (50 mm/s speed and 1 mV gain = 1 cm). Results: In some affected animals, especially in cases of compensated dilated cardiomyopathy, leukocytosis was noted. In patients with dilated cardiomyopathy complicated by heart failure syndrome of various functional classes, the number of neutrophils was significantly increased, and the number of lymphocytes was decreased by 1.9-2.1 times when compared with those in clinically normal animals. In dogs with dilated cardiomyopathy, neutrophilic leukocytosis develops with a simple regenerative shift to the left. The results of immunological studies indicate that dogs with dilated cardiomyopathy develop T lymphocytopenia as compared with clinically normal animals. Conclusion: The central component of heart failure syndrome in dogs with dilated cardiomyopathy is the activation of the neurohumoral system and immune-mediated inflammation. The development of CHF in dogs with dilated cardiomyopathy is caused by the progressive loss of cardiomyocytes, apoptosis, remodeling of the left ventricle, systolic and diastolic dysfunction, arrhythmias, reduced cerebral blood flow, involvement of other key internal organs, and intestinal dysbiosis.

Changes of inflammatory and oxidative stress biomarkers in dogs with different stages of heart failure

“…Although both of them are commonly considered non-inflammatory conditions [ 6 , 7 ], studies have found increased circulating inflammatory cytokines in dogs and humans with CHF due to MMVD [ 8 , 9 ] and DCM [ 7 , 10 ]. Increased expression and release of inflammatory cytokines such as tumour necrosis factor (TNF-α), as well as serum C-reactive protein (CRP), have been described in humans [ 11 , 12 ] and dogs with CHF [ 13 ].…”

Left ventricular myocardial remodeling in dogs with mitral valve endocardiosis

“…Hereditary and acquired pathologies in animals of both non-infectious and contagious etiology are very diverse and complex, characterized by various forms of manifestations, which are often difficult to diagnose and require special approaches in treatment and prevention [1][2][3][4][5][6].…”

“…Endocardiosis in dogs is characterized by chronic myxomatous degeneration of the mitral valve, which leads to thickening and incomplete closure of its cusps and the development of mitral regurgitation whose severity is the main determinant of disease progression. It should be noted that most dogs with endocardiosis have an asymptomatic course for many years or even throughout their lives [4,9,10]. However, with progressive mitral regurgitation, severe complications can arise in the form of development of left-sided and then rightsided congestive chronic heart failure (CHF), usually secondary to the high pulmonary arterial hypertension syndrome [5].…”

Changes of inflammatory and oxidative stress biomarkers in dogs with different stages of heart failure

“…Although both of them are commonly considered non-in ammatory conditions (6,7), studies have found increased circulating in ammatory cytokines in dogs and humans with CHF due to MMVD (8,9) and DCM (7,10). Increased expression and release of in ammatory cytokines such as tumour necrosis factor (TNF-α), as well as serum C-reactive protein (CRP), have been described in humans (11,12) and dogs with CHF (13).…”