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

Abstract

Cardiac atrophy is the most common complication of prolonged application of the left ventricle (LV) assist device (LVAD) in patients with advanced heart failure (HF). Our aim was to evaluate the course of unloading-induced cardiac atrophy in rats with failing hearts, and to examine if increased isovolumic loading obtained by intraventricular implantation of an especially designed spring expander would attenuate this process. Heterotopic abdominal heart transplantation (HTx) was used as a rat model of heart unloading. HF was induced by volume overload achieved by creation of the aorto-caval fistula (ACF). The degree of cardiac atrophy was assessed as the weight ratio of the heterotopically transplanted heart (HW) to the control heart. Isovolumic loading was increased by intraventricular implantation of a stainless steel three-branch spring expander. The course of cardiac atrophy was evaluated on days 7, 14, 21, and 28 after HTx. Seven days unloading by HTx in failing hearts sufficed to substantially decrease the HW (−59 ± 3%), the decrease progressed when measured on days 14, 21, and 28 after HTx. Implantation of the spring expander significantly reduced the decreases in whole HW at all the time points (−39 ± 3 compared with −59 ± 3, −52 ± 2 compared with −69 ± 3, −51 ± 2 compared with –71 ± 2, and −44 ± 2 compared with −71 ± 3%, respectively; P<0.05 in each case). We conclude that the enhanced isovolumic heart loading obtained by implantation of the spring expander attenuates the development of unloading-induced cardiac atrophy in the failing rat heart.

Impaired renal autoregulation and pressure-natriuresis: any role in the development of heart failure in normotensive and angiotensin II-dependent hypertensive rats?

“…In separate appropriately matched four experimental groups ( n = 8 in each), i.e. sham-operated HanSD rats, sham-operated TGR, ACF HanSD rats and ACF TGR, the hearts and kidneys were subjected to histological examination of the myocardium and renal cortex as described previously [ 26 , 43 – 45 ].…”

“…Since there were no significant differences in the cardiomyocyte width between the layers, the data from the subendocardium, midmyocardium, and subepicardium were pooled, as was also practiced by other investigators [ 46 ]. Analysis of LV and RV fibrosis was performed in sections stained with Picrosirius red (Direct Red 80, Sigma Aldrich, MO, USA) as described in detail previously [ 43 ]. The interstitial collagen was analyzed in polarized light using 10 images of the LV and RV scanned from a midmyocardium, without perivascular areas (magnification 200x, microscope Nikon eclipse Ni-E, camera Nikon DS-L3, Tokyo, Japan).…”

Renal sympathetic denervation improves pressure-natriuresis relationship in cardiorenal syndrome: insight from studies with Ren-2 transgenic hypertensive rats with volume overload induced using aorto-caval fistula

“…Since there were no significant differences in the cardiomyocyte width between the layers, the data from the subendocardium, midmyocardium, and subepicardium were pooled, as was also practiced by other investigators [60]. Analysis of LV fibrosis was performed in sections stained with Picrosirius red (Direct Red 80, Sigma Aldrich, MO, USA) as described in detail previously [61]. The interstitial collagen was analyzed in polarized light using 10 images of the LV scanned from a midmyocardium, without perivascular areas (magnification 200x, microscope Nikon eclipse Ni-E, camera Nikon DS-L3, Tokyo, Japan).…”

Does Myocardial Atrophy Represent Anti-Arrhythmic Phenotype?

“…In general, smaller myocytes exhibit the highest growth potential, whereas larger myocytes exhibit the highest potential to atrophy [ 2 ]. Partial and total unloading affects the myocardial remodelling of non-failing hearts in a rodent model to different extents in myocardial atrophy, fibrosis, glucose metabolism and mechanical study [ 132 ] Thus, cardiac recovery is possible by means of mechanical loading [ 136 , 137 ] yet remains rare. In fact, therapeutic approaches that aim to prevent/attenuate myocardial atrophy along with associated abnormalities are still rare, and these abnormalities can result in depressed contractility.…”