Effects of Increased Myocardial Tissue Concentration of Myristic, Palmitic and Palmitoleic Acids on the Course of Cardiac atrophy of the Failing Heart Unloaded by Heterotopic Transplantation

Abstract

The present experiments were performed to evaluate if increased heart tissue concentration of fatty acids, specifically myristic, palmitic and palmitoleic acids that are believed to promote physiological heart growth, can attenuate the progression of unloading-induced cardiac atrophy in rats with healthy and failing hearts. Heterotopic abdominal heart transplantation (HTx) was used as a model for heart unloading. Cardiac atrophy was assessed from the ratio of the native- to-transplanted heart weight (HW). The degree of cardiac atrophy after HTx was determined on days 7, 14, 21 and 28 after HTx in recipients of either healthy or failing hearts. HTx of healthy hearts resulted in 23±3, 46±3, 48±4 and 46±4 % HW loss at the four time-points. HTx of the failing heart resulted in even greater HW losses, of 46±4, 58±3, 66±2 and 68±4 %, respectively (P<0.05). Activation of “fetal gene cardiac program” (e.g. beta myosin heavy chain gene expression) and “genes reflecting cardiac remodeling” (e.g. atrial natriuretic peptide gene expression) after HTx was greater in failing than in healthy hearts (P<0.05 each time). Exposure to isocaloric high sugar diet caused significant increases in fatty acid concentrations in healthy and in failing hearts. However, these increases were not associated with any change in the course of cardiac atrophy, similarly in healthy and post-HTx failing hearts. We conclude that increasing heart tissue concentrations of the fatty acids allegedly involved in heart growth does not attenuate the unloading-induced cardiac atrophy.

Isovolumic loading of the failing heart by intraventricular placement of a spring expander attenuates cardiac atrophy after heterotopic heart transplantation

“…It will also be noticed that a comparison of the degree of cardiac atrophy in the failing heart (the present study) and that observed in our recent study in the healthy (i.e. non-failing) heart [ 44 ] shows clearly that unloading-induced cardiac atrophy is distinctly more pronounced in the failing heart. These findings are critically important for at least two reasons.…”

“…In addition, samples of LV myocardium were frozen in liquid nitrogen and stored at −80°C until analysis of the ‘fetal cardiac gene’ expressions, as described in detail previously. This was performed on days 7 and 28 after heterotopic HT x [ 44 ]. Briefly, the relative gene expression was calculated by the ΔΔ C t method and results were expressed as the n-fold difference in gene expression relative to β-actin mRNA of the transplanted-to-control heart (i.e.…”

Intraventricular placement of a spring expander does not attenuate cardiac atrophy of the healthy heart induced by unloading via heterotopic heart transplantation

“…This improvement was observed in the failing heart i.e. the one derived from animals with established advanced HF (Pokorný et al 2018b). Moreover, we have also found that the natural course of unloading-induced cardiac atrophy is different in the healthy and failing hearts (Pokorný et al 2018a).…”

“…the one derived from animals with established advanced HF (Pokorný et al 2018b). Moreover, we have also found that the natural course of unloading-induced cardiac atrophy is different in the healthy and failing hearts (Pokorný et al 2018a). On the whole, the basic question is whether an enhancement of isovolumic loading can be used as a general therapeutic approach to prevent or at least attenuate the development of unloading-induced cardiac atrophy.…”

“…Many attempts have been made to minimize the said detrimental effect of long-term LVAD use, however, the therapeutic effects were not satisfactory, which underscores the need for further search for new treatment approaches (Benke et al 2017, Fu et al 2016, Geen et al 1994, Heckle et al 2016, Navarathnarajah et al 2014, Pokorný et al 2014, Pokorný et al 2018a. We reported recently that implantation of the stainless steel spring expander into the LV (it provides sufficient isovolumic loading without impairing LV ejection function) attenuated the process of unloading-induced cardiac atrophy after heterotopic HT x onto the abdominal aorta of an isogenic rat recipient (a recognized model to study effects of mechanical heart unloading).…”