Aims: 

Pathophysiology of heart failure and identification of new biomarkers is still subject of research. Recently, a number of different peptides, produced also by the heart, has been appointed as potential biomarkers, including the cardioprotective ghrelin (GHR) and adrenomedullin (ADM), that is vasodilatator and has natriuretic effect. The aim of our study was setting of large animal model of chronic heart failure and investigation of kinetics of the above peptides during the evolution of heart failure.

Methods: 

Fast ventricular pacing (240/min) was applied in canines (n=9) after implantation of pacemakers. During 4 weeks of follow-up echocardiographic examinations were performed and functional stage was estimated. ADM and active GHR levels were measured by ELISA from blood samples.

Results: 

The dogs reached the stage NYHA IV-equal status after 22±4 days of pacing. At echocardiography severe left ventricular functional decline was found in every aminal (average±SEM: EF: 23±5% vs. 62±3%, p<0.01), left ventricular (LVEDD: 45±0 vs. 37±2 mm, p<0.01) and right ventricular dilatation (RVEDD: 25±2 vs. 21±1 mm, p<0.01), and cumulative mitral and tricuspidal regurgitation was developed. During development of chronic heart failure plasma level of both peptides got elevated significantly (GHR: 1655±286 vs. 952±139 pg/ml; ADM: 440±53 vs. 292±48 pg/ml, p<0.01). Positive correlation was found between the plasma level of ghrelin and left ventricular end-diastolic and end-systolic diameter (LVEDD: r=0.44, p<0.05; LVEDS: r=0.45, p<0.05).

Conclusion: 

The applied high frequency right ventricular pacing is a feasible method for establishing a reproducible model of chronic heart failure and it can be suitable for experimental tests of new treatments.

Support: 

NKTH OTKA K-67892 grant