Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 May 6;26(9):4422.
doi: 10.3390/ijms26094422.

Effects of Left Ventricular Unloading on Cardiac Function, Heart Failure Markers, and Autophagy in Rat Hearts with Acute Myocardial Infarction

Ryota Azuma  1 , Yasushige Shingu  1 , Jingwen Gao  1 , Satoru Wakasa  1
Affiliations

Effects of Left Ventricular Unloading on Cardiac Function, Heart Failure Markers, and Autophagy in Rat Hearts with Acute Myocardial Infarction

Ryota Azuma et al. Int J Mol Sci. .

Abstract

Percutaneous ventricular assist devices are utilized in cases of cardiogenic shock following acute myocardial infarction (AMI). However, the mechanism underlying the beneficial effects of LV unloading in AMI remains unclear. This study aimed to examine the impact of LV unloading on cardiac function, heart failure markers, and protein degradation (autophagy and ubiquitin-proteasome system: UPS) post AMI in rats. Nine-week-old male Lewis rats were randomized into non-AMI, AMI, non-AMI with LV unloading, and AMI with LV unloading groups. LV unloading was achieved through heterotopic heart-lung transplantation. Rats were euthanized 2 and 14 days after the procedure. Cardiac functional assessment was performed using Langendorff heart perfusion. RT-PCR and Western blot analyses were conducted using the LV myocardium. The rate pressure product was comparable between the non-AMI with LV unloading group and the AMI with LV unloading at 14 days. The atrial natriuretic factor tended to be suppressed by LV unloading. LV unloading had reducing effects on the expressions of p62, selectively degraded during autophagy, both 2 and 14 days after AMI. There was no effect on the parameters for the UPS. LV unloading has a mitigating effect on the deterioration of cardiac function following AMI. Autophagy, which was suppressed by AMI, was ameliorated by LV unloading.

Keywords: LV unloading; acute myocardial infarction; autophagy.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflicts of interest. The funder had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
Cardiac functional parameters of Langendorff heart perfusion in the 2- (A) and 14-day (B) models. AMI, acute myocardium infarction; HR, heart rate; RPP, rate pressure product; UL, unloading. n = 4–6 for each group. Data are expressed as mean and SEM. * p < 0.05 and ** p < 0.01 (post hoc Bonferroni). The p values in the figure are those of the interaction (AMI × UL) and main effects (AMI or UL) in the two-way ANOVA.
Figure 2
Figure 2
LV weight and histological data in the 2- (A) and 14-day (B) models. AMI, acute myocardium infarction; HE, hematoxylin eosin; MT, Masson’s trichrome; UL, unloading. n = 4–6 for each group. Data are expressed as mean and SEM. * p < 0.05, *** p < 0.001, and **** p < 0.0001 (post hoc Bonferroni). The scale bars indicate 100 μm. The p values in the figure are those of the interaction (AMI × UL) and main effects (AMI or UL) in the two-way ANOVA.
Figure 3
Figure 3
Myocardial gene expressions of MHC, ANF, BNP, and SERCA2 in the 2- (A) and 14-day (B) models. AMI, acute myocardium infarction; ANF, atrial natriuretic factor; BNP, brain natriuretic peptide, MHC, myosin heavy chain; SERCA2, sarco/endoplasmic reticulum Ca2+-ATPase; UL, unloading. n = 4–6 for each group. Data are expressed as mean and SEM. * p < 0.05 and ** p < 0.01 (post hoc Bonferroni). The p values in the figure are those of the interaction (AMI × UL) and main effects (AMI or UL) in the two-way ANOVA.
Figure 4
Figure 4
Myocardial expressions of autophagy-related proteins by Western blot in the 2- (A) and 14-day (B) models. AMI, acute myocardium infarction; AMPK, AMP-activated protein kinase; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; LC3-II, microtubule-associated light chain 3 II; pAMPK, phosphorylated AMPK; UL, unloading. n = 4 for each group. Data are expressed as mean and SEM. * p < 0.05 and ** p < 0.01 (post hoc Bonferroni). The p values in the figure are those of the interaction (AMI × UL) and main effects (AMI or UL) in the two-way ANOVA.
Figure 5
Figure 5
Parameters of UPS and protein synthesis in the 2- (A) and 14-day (B) models. K48 is a marker of polyubiquitination. The ratio of pAKT/AKT is a marker of protein synthesis. Atrogin1 and MuRF1 are ubiquitin ligases. K48 and AKT were assessed with Western blot; Atrogin1 and MuRF1 were evaluated with RT-PCR. AMI, acute myocardium infarction; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; UL, unloading. n = 4–6 for each group. Data are expressed as mean and SEM. * p < 0.05 (post hoc Bonferroni). The p values in the figure are those of the interaction (AMI × UL) and main effects (AMI or UL) in the two-way ANOVA.
Figure 6
Figure 6
Experimental protocol of the 2- (A) and 14-day (B) models. Nine-week-old male Lewis rats were randomized into four groups (n = 4–6 per group): non-AMI, AMI, non-AMI with LV unloading, and AMI with LV unloading. Rats were euthanized 2 and 14 days after the operation and ex vivo cardiac functional assessment was performed by Langendorff system. AMI, acute myocardium infarction; HTx, heart transplantation; LAD, left anterior descending artery; UL, unloading.
Figure 7
Figure 7
Schema of the partial LV unloading procedure (A) and blood flow in the donor heart (B). (A) The donor heart was extracted with lungs. Two sutures for the abdominal and ascending aorta were ligated (7-0 polypropylene) at both ends of the incision (1). The left side of the anastomosis was created by a running suture (2). The donor heart and lungs were turned over to the left side. The right side of the anastomosis was created by a running suture (3). (B) The LV was partially unloaded because the LV was loaded only by the coronary perfusion volume. The red and blue arrows indicate oxygenated and unoxygenated blood, respectively.
See this image and copyright information in PMC

References

    1. Tsao C.W., Aday A.W., Almarzooq Z.I., Anderson C.A.M., Arora P., Avery C.L., Baker-Smith C.M., Beaton A.Z., Boehme A.K., Buxton A.E., et al. Heart Disease and Stroke Statistics-2023 Update: A Report From the American Heart Association. Circulation. 2023;147:e93–e621. doi: 10.1161/CIR.0000000000001123. - DOI - PMC - PubMed
    1. Masoudi F.A., Ponirakis A., de Lemos J.A., Jollis J.G., Kremers M., Messenger J.C., Moore J.W.M., Moussa I., Oetgen W.J., Varosy P.D., et al. Trends in U.S. Cardiovascular Care: 2016 Report From 4 ACC National Cardiovascular Data Registries. J. Am. Coll. Cardiol. 2017;69:1427–1450. doi: 10.1016/j.jacc.2016.12.005. - DOI - PubMed
    1. Thiele H., Ohman E.M., de Waha-Thiele S., Zeymer U., Desch S. Management of cardiogenic shock complicating myocardial infarction: An update 2019. Eur. Heart J. 2019;40:2671–2683. doi: 10.1093/eurheartj/ehz363. - DOI - PubMed
    1. Manzi L., Sperandeo L., Forzano I., Castiello D.S., Florimonte D., Paolillo R., Santoro C., Mancusi C., Di Serafino L., Esposito G., et al. Contemporary Evidence and Practice on Right Heart Catheterization in Patients with Acute or Chronic Heart Failure. Diagnostics. 2024;14:136. doi: 10.3390/diagnostics14020136. - DOI - PMC - PubMed
    1. McDonagh T.A., Metra M., Adamo M., Gardner R.S., Baumbach A., Bohm M., Burri H., Butler J., Čelutkienė J., Chioncel O., et al. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur. Heart J. 2021;42:3599–3726. doi: 10.1093/eurheartj/ehab368. - DOI - PubMed

LinkOut - more resources