Book of Abstracts - New Frontiers 2022

Abstracts of poster presentations

TRANDOLAPRIL EFFECT ON THE RAT MYOCARDIUM IN EXPERIMENTAL VOLUME OVERLOAD HEART FAILURE D. Jarkovská 1,2 , M. Miklovič 3,4 , J. Švíglerová 1,2 , L. Červenka 3,4 , P. Škaroupková 3 , V. Melenovský 5 , M. Štengl 1,2 1 Department of Physiology, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic; 2 Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic; 3 Center for Experimental Medicine, Institute for Clinical and Experimental Medicine, Prague, Czech Republic; 4 Department of Pathophysiology, 2nd Faculty of Medicine, Charles University, Prague, Czech Republic; 5 Department of Cardiology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic Heart failure (HF) is currently defined as a clinical syndrome with symptoms and/or signs caused by a structural and/or functional cardiac abnormality and corroborated by elevated natriuretic peptide levels and/or objective evidence of pulmonary or systemic congestion. The renin-angiotensin-aldosterone-system plays a significant role in HF progression which is proved by the beneficial effect of the drugs affecting this signaling pathway, e.g. angiotensin-converting enzyme (ACE) inhibitors. Rats with chronic volume overload due to aortocaval fistula (ACF) represent a well-characterized, reproducible and simple model of heart failure. This study aimed to investigate the effect of ACE inhibition on various remodeling processes occurring in rats with volume overload induced by ACF. The 62 Hannover Sprague-Dawley male rats were divided into three groups: sham-operated (n = 25), ACF (n = 20) and ACF with ACE inhibitor trandolapril treatment (n = 18). ACF was induced surgically using a needle technique in 8 weeks old animals. In the trandolapril group, the treatment (6 mg/l of trandolapril in drinking water) started 4 weeks after the operation and continued for 20 weeks until the end of the experiment. 24 weeks after the surgery, the animals had been anesthetized before the ECG recording and echocardiography were performed. The rats were sacrificed by cervical dislocation and their hearts were excised and used for further experiments. Membrane potential and contraction force were recorded on multicellular preparations from the left ventricle. The calcium transients and sarcomeric shortening were measured on enzymatically dissociated ventricular cardiomyocytes using a fluorescent dye Fura-2. In ACF rats, trandolapril treatment significantly improved survival rate, however, did not influence cardiac hypertrophy. In the ACF group, QRS complex and ventricular action potential prolongation together with spontaneous activity in isolated ventricular cardiomyocytes were observed. All these proarrhythmic electrophysiological changes were attenuated by trandolapril treatment which was associated with a lower mortality rate in this group. On the other hand, ACE inhibition did not have any effect on increased cardiac output, eccentric cardiac hypertrophy and intracellular calcium levels in ACF animals. The volume overload and the pharmacological treatment did not induce any changes in contractility in vitro on both multicellular and cellular levels. ACE inhibition was shown to effectively suppress the proarrhythmic remodeling while not affecting the cardiac hypertrophy in volume overload.

Keywords: heart failure, cardiac remodeling, renin-angiotensin-aldosterone system, trandolapril, rat

Funding:This work was supported by the Cooperatio Program, research area Medical Diagnostics and Basic Medical Sciences, and by the Ministry of Health of the Czech Republic grant no. AZV NU20-02-00052 and grant no. AZV NU21-02 00402.

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