Effects of Trandolapril on Structural, Contractile and Electrophysiological Remodeling in Experimental Volume Overload Heart Failure

Abstract

Chronic volume overload induces multiple cardiac remodeling processes that finally result in eccentric cardiac hypertrophy and heart failure. We have hypothesized that chronic angiotensin-converting enzyme (ACE) inhibition by trandolapril might affect various remodeling processes differentially, thus allowing their dissociation. Cardiac remodeling due to chronic volume overload and the effects of trandolapril were investigated in rats with an aortocaval fistula (ACF rats). The aortocaval shunt was created using a needle technique and progression of cardiac remodeling to heart failure was followed for 24 weeks. In ACF rats, pronounced eccentric cardiac hypertrophy and contractile and proarrhythmic electrical remodeling were associated with increased mortality. Trandolapril substantially reduced the electrical proarrhythmic remodeling and mortality, whereas the effect on cardiac hypertrophy was less pronounced and significant eccentric hypertrophy was preserved. Effective suppression of electrical proarrhythmic remodeling and mortality but not hypertrophy indicates that the beneficial therapeutic effects of ACE inhibitor trandolapril in volume overload heart failure might be dissociated from pure antihypertrophic effects.

Impact of volume overload on cardiac connexin-43 and extracellular matrix of normotensive and hypertensive Ren-2 transgenic rats: Effects of treatment with Trandolapril and Losartan

“…In accordance with ACF-induced increase of mitochondrial ROS production 28,29 . ACF-induced increases in right and left ventricle mass index, in HSD as well as TGR, as also shown previously in normotensive rats 10,15,27,30,31 . These parameters were utilized as markers of hypertrophy 32 .…”

“…Treatment with either drug supressed circulating ANP and TBARS levels in both heart ventricles and reduced heart mass index, including right and left ventricles regardless the rat strain. Likewise in HSD rats treated with trandolapril 30 . Moreover, treatment increased alkaline phosphatase activity in arterial part of capillary network in HSD as well as TGR that may contribute to improvement of heart function 34 .…”

The impact of phosphodiesterase‐5 inhibition or angiotensin‐converting enzyme inhibition on right and left ventricular remodeling in heart failure due to chronic volume overload

“…Jarkovska et al suggested the anti-arrhythmic effect of ACEi in ACF rats. 53 The present study has several limitations. Only the resting hemodynamics was tested, because of technical reasons we did not perform preload changing maneuvers (vena cava balloon inflation), and therefore we cannot report arterial and ventricular elastance values.…”

Regulation of Prepro-NeuropeptideW/B and Its Receptor in the Heart of ZDF Rats: An Animal Model of Type II DM

“…Sarcometic contractions and calcium transients were measured as described previously [ 41 ]. The cardiomyocytes from the left ventricle ( n = 16–23 in each group) were incubated with 2-μmol/L-Fura-2-AM Tyrode solution for 20 min and then washed with Tyrode solution repeatedly.…”