Jarkovská Dagmar, Miklovič Matúš, Švíglerová Jitka, Červenka Luděk, Škaroupková Petra, Melenovský Vojtěch, Štengl Milan
Department of Physiology, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czechia.
Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czechia.
Front Pharmacol. 2021 Sep 10;12:729568. doi: 10.3389/fphar.2021.729568. eCollection 2021.
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.
慢性容量超负荷会引发多种心脏重塑过程，最终导致离心性心肌肥大和心力衰竭。我们推测，群多普利对慢性血管紧张素转换酶（ACE）的抑制作用可能会对各种重塑过程产生不同影响，从而使其相互分离。我们在患有主动脉腔静脉瘘的大鼠（ACF大鼠）中研究了慢性容量超负荷引起的心脏重塑以及群多普利的作用。采用针刺技术建立主动脉腔静脉分流，并观察心脏重塑进展至心力衰竭的过程，持续24周。在ACF大鼠中，明显的离心性心肌肥大以及收缩性和促心律失常性电重塑与死亡率增加相关。群多普利显著降低了促心律失常性电重塑和死亡率，而对心肌肥大的影响较小，且明显的离心性肥大得以保留。有效抑制促心律失常性电重塑和死亡率而非肥大表明，ACE抑制剂群多普利在容量超负荷心力衰竭中的有益治疗作用可能与单纯的抗肥厚作用相分离。
