Abstract 515: Expression of Leptin, Adiponectin, and Activation of AMP Kinase in Failing and Mechanically Unloaded Human Hearts

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Kenneth McGaffin ◽  
Benjamin Burkhead ◽  
Gregory Gibson ◽  
Christine Moravec ◽  
Charles McTiernan
Keyword(s):  
Fold Increase ◽  
Left Ventricular ◽  
Ampk Activation ◽  
Amp Kinase ◽  
Human Heart Failure ◽  
Ventricular Assist ◽  
Atp Production ◽  
Protein Levels ◽  
Mechanical Unloading ◽  
End Stage

Introduction: The failing heart displays contractile dysfunction, increased workload and energy demands, and a switch in substrate utilization for ATP production from free fatty acid to glucose oxidation. ATP production is regulated by AMP Kinase (AMPK). In skeletal muscle, the cytokines leptin (OB) and adiponectin (AD) stimulate AMPK activity and result in preferential glucose metabolism. Both OB and AD are elevated in human heart failure (HF), but it is unknown whether these cytokines may alter AMPK activation in the failing and/or mechanically unloaded heart. Hypothesis : In human HF, elevated OB and AD levels: 1) are in part due to increased production by the cardiomyocyte; 2) are associated with cardiac AMPK activation; and 3) are downregulated under conditions of reduced workload and ATP requirement such as occurs with mechanical unloading. Methods/Results: Left ventricular tissue was obtained from 5 non-failing (NF), 10 end stage failing (F), and 8 paired pre/post ventricular assist device (VAD) patients. Results reported are fold change ± SEM relative to NF or pre VAD, compared by t-test . Relative to NF, F hearts showed (Real-time PCR) increased mRNA for BNP (4.4±0.4, P =0.04), OB (5.4±0.3, P =0.03), OBR (7.3±0.2, P =0.01) and AD (9.1±0.9, P =0.01), while levels of an unrelated gene, the grehlin receptor, were decreased (0.10±0.01, P =0.01). Immunoblotting confirmed similar changes in OB, OBR and AD protein levels, and immunoflurescence localized these proteins to the cardiomyocyte. Increased activation of AMPKα was observed in F hearts (1.9±0.2 fold increase vs NF, P =0.02) as assessed by the ratio of phosphorylated to total AMPKα. In paired pre and post VAD supported hearts, these changes were reversed after mechanical unloading as decreased BNP (0.020±0.001, P =0.01), OB (0.030±0.001, P =0.03), OBR (0.25±0.01, P =0.02) and AD (0.22±0.01, P =0.04) mRNAs were seen relative to the pre VAD state, whereas increased grehlin receptor mRNA was observed (7.6±0.5, P <0.01 ) Further, relative to the pre VAD heart, post VAD showed a 1.7±0.2 fold ( P =0.04) decrease in the activation of AMPK. Conclusions: OB and AD are produced by failing cardiomyocytes and may contribute to preferential use of glucose for energy production in HF through activation of AMPK.

scholarly journals Differential Regulation of MicroRNAs in End-Stage Failing Hearts Is Associated with Left Ventricular Assist Device Unloading

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Cristina Barsanti ◽  
Maria Giovanna Trivella ◽  
Romina D’Aurizio ◽  
Mariama El Baroudi ◽  
Mario Baumgart ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Left Ventricular ◽  
Ventricular Assist Devices ◽  
Reverse Remodeling ◽  
Left Ventricular Assist Devices ◽  
Ventricular Assist ◽  
Off Pump ◽  
Mechanical Unloading ◽  
Left Ventricular Assist ◽  
End Stage

Mechanical unloading by left ventricular assist devices (LVADs) in advanced heart failure (HF), in addition to improving symptoms and end-organ perfusion, is supposed to stimulate cellular and molecular responses which can reverse maladaptive cardiac remodeling. As microRNAs (miRNAs) are key regulators in remodeling processes, a comparative miRNA profiling in transplanted hearts of HF patients with/without LVAD assistance could aid to comprehend underlying molecular mechanisms. Next generation sequencing (NGS) was used to analyze miRNA differential expression in left ventricles of HF patients who underwent heart transplantation directly (n=9) or following a period of LVAD support (n=8). After data validation by quantitative real-time PCR, association with functional clinical parameters was investigated. Bioinformatics’ tools were then used for prediction of putative targets of modulated miRNAs and relative pathway enrichment. The analysis revealed 13 upregulated and 10 downregulated miRNAs in failing hearts subjected to LVAD assistance. In particular, the expression level of some of them (miR-338-3p, miR-142-5p and -3p, miR-216a-5p, miR-223-3p, miR-27a-5p, and miR-378g) showed correlation with off-pump cardiac index values. Predicted targets of these miRNAs were involved in focal adhesion/integrin pathway and in actin cytoskeleton regulation. The identified miRNAs might contribute to molecular regulation of reverse remodeling and heart recovery mechanisms.

Rescue extracorporeal life support as a bridge to durable left ventricular assist device

2021 ◽  
pp. 039139882110538
Author(s):  
Alina Zubarevich ◽  
Konstantin Zhigalov ◽  
Marcin Szczechowicz ◽  
Arian Arjomandi Rad ◽  
Robert Vardanyan ◽  
...  
Keyword(s):  
Heart Failure ◽  
Life Support ◽  
Extracorporeal Life Support ◽  
Left Ventricular ◽  
Organ Function ◽  
Assist Device ◽  
Ventricular Assist ◽  
Left Ventricular Assist ◽  
End Stage Heart Failure ◽  
End Stage

Background: The ideal timing of a durable assist device implantation in patients with end-stage heart failure presenting with INTERMACS profile I is still controversial. The data on extracorporeal life support (ECLS) bridge to durable left ventricular assist device (LVAD) in these patients is limited. Materials and methods: We retrospectively analyzed the outcomes of 35 patients in acute cardiogenic shock (CS) who, between December 2013 and September 2020, were bridged with ECLS to durable LVAD. The mean age was 52.3 ± 12.0 years. The primary endpoints of this study were in-hospital, 30-day, 6-month, and 1-year mortality. The secondary endpoint was the development of any postoperative adverse events and other characteristics during the follow-up period. We also assessed the impact of the rescue ECLS on the recovery of the end-organ function. Results: In-hospital, 30-day, 6-month, and 1-year survival was 65.6%, 75.9%, 69.2%, and 62.7% respectively. The median time on ECLS was 7 days (IQR 5.0–13.0). We observed a high incidence of a severe right heart failure (22.9%), acute kidney injury on dialysis (68.6%), and respiratory failure (77.1%). Bridge with ECLS provided a significant recovery of liver and kidney function prior to durable LVAD implantation. Conclusion: The concept of bridging patients presenting in end-stage heart failure and cardiogenic shock with ECLS prior to durable LVAD implantation is a feasible method to ensure acceptable survival rates and significant recovery of the end-organ function.

Pulsatile Flow in Patients With a Novel Nonpulsatile Implantable Ventricular Assist Device

Circulation ◽  
2000 ◽  
Vol 102 (suppl_3) ◽  
Author(s):  
Evgenij V. Potapov ◽  
Matthias Loebe ◽  
Boris A. Nasseri ◽  
Hendryk Sinawski ◽  
Andreas Koster ◽  
...  
Keyword(s):  
Ejection Fraction ◽  
Pulsatile Flow ◽  
Transcranial Doppler ◽  
Continuous Flow ◽  
Left Ventricular ◽  
Ventricular Assist Devices ◽  
Ventricular Assist ◽  
Doppler Signals ◽  
End Stage ◽  
Cranial Arteries

Background —Ventricular assist devices (VADs) are an accepted therapy for patients with end-stage heart failure. The implantable devices that are available produce a pulsatile flow and are very large. In 6 patients, beginning in November 1998, we started to use the continuous-flow implantable DeBakey VAD device, which weighs 93 g. To detect the flow in peripheral vessels, we measured transcranial Doppler signals in patients after implantation. Methods and Results —Transcranial Doppler studies were performed with the MULTI-DOP X4 device with two 2-MHz probes (for the middle cranial arteries) in 4 patients for up to 12 weeks twice weekly after implantation. The blood velocity was measured, and the pulsation index (PI) calculated. The measured pump flow and rotations per minute were registered. The preoperative echocardiographic assessment values were compared with those acquired 6 weeks after implantation. The PI increased continually in all patients after VAD implantation, left ventricular (LV) ejection fraction did not improve, but right ventricular (RV) ejection fraction after implantation improved compared with preoperative values. The LV end-diastolic diameter after implantation decreased between 11% and 46% intraindividually. There was no correlation between PI and blood pressure or, except in 1 patient, between PI and blood flow through the VAD. Conclusions —The DeBakey VAD unloads the LV, which leads to a decrease in LV end-diastolic LV diameter and to the restoration of RV function. The unloaded LV and partially recovered RV provide a nearly physiological pulsatile flow despite the continuous flow of the VAD. Pulsatility is independent of peripheral vascular resistance. The first clinical experience with the DeBakey VAD was positive and has resulted in its continued use.

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