174 Early beneficial effects of vasopeptidase inhibtion n an experimental model of heart failure

2003 ◽  
Vol 2 (1) ◽  
pp. 33-34
Author(s):  
B SHIVALKAR ◽  
B MEURIS ◽  
R VANBENEDEN ◽  
J KETESLEGERS ◽  
F BECKERS ◽  
...  
2020 ◽  
Vol 18 (2) ◽  
pp. 148-157 ◽  
Author(s):  
Triantafyllos Didangelos ◽  
Konstantinos Kantartzis

The cardiac effects of exogenously administered insulin for the treatment of diabetes (DM) have recently attracted much attention. In particular, it has been questioned whether insulin is the appropriate treatment for patients with type 2 diabetes mellitus and heart failure. While several old and some new studies suggested that insulin treatment has beneficial effects on the heart, recent observational studies indicate associations of insulin treatment with an increased risk of developing or worsening of pre-existing heart failure and higher mortality rates. However, there is actually little evidence that the associations of insulin administration with any adverse outcomes are causal. On the other hand, insulin clearly causes weight gain and may also cause serious episodes of hypoglycemia. Moreover, excess of insulin (hyperinsulinemia), as often seen with the use of injected insulin, seems to predispose to inflammation, hypertension, dyslipidemia, atherosclerosis, heart failure, and arrhythmias. Nevertheless, it should be stressed that most of the data concerning the effects of insulin on cardiac function derive from in vitro studies with isolated animal hearts. Therefore, the relevance of the findings of such studies for humans should be considered with caution. In the present review, we summarize the existing data about the potential positive and negative effects of insulin on the heart and attempt to answer the question whether any adverse effects of insulin or the consequences of hyperglycemia are more important and may provide a better explanation of the close association of DM with heart failure.


2021 ◽  
Vol 22 (11) ◽  
pp. 5863
Author(s):  
Giuseppe Palmiero ◽  
Arturo Cesaro ◽  
Erica Vetrano ◽  
Pia Clara Pafundi ◽  
Raffaele Galiero ◽  
...  

Heart failure (HF) affects up to over 20% of patients with type 2 diabetes (T2DM), even more in the elderly. Although, in T2DM, both hyperglycemia and the proinflammatory status induced by insulin resistance are crucial in cardiac function impairment, SGLT2i cardioprotective mechanisms against HF are several. In particular, these beneficial effects seem attributable to the significant reduction of intracellular sodium levels, well-known to exert a cardioprotective role in the prevention of oxidative stress and consequent cardiomyocyte death. From a molecular perspective, patients’ exposure to gliflozins’ treatment mimics nutrient and oxygen deprivation, with consequent autophagy stimulation. This allows to maintain the cellular homeostasis through different degradative pathways. Thus, since their introduction in the clinical practice, the hypotheses on SGLT2i mechanisms of action have changed: from simple glycosuric drugs, with consequent glucose lowering, erythropoiesis enhancing and ketogenesis stimulating, to intracellular sodium-lowering molecules. This provides their consequent cardioprotective effect, which justifies its significant reduction in CV events, especially in populations at higher risk. Finally, the updated clinical evidence of SGLT2i benefits on HF was summarized. Thus, this review aimed to analyze the cardioprotective mechanisms of sodium glucose transporter 2 inhibitors (SGLT2i) in patients with HF, as well as their clinical impact on cardiovascular events.


2004 ◽  
Vol 287 (3) ◽  
pp. H1003-H1012 ◽  
Author(s):  
Keisuke Kawai ◽  
Fuzhong Qin ◽  
Junya Shite ◽  
Weike Mao ◽  
Shuji Fukuoka ◽  
...  

The present study was carried out to determine whether beneficial effects of carvedilol in congestive heart failure (CHF) are mediated via its β-adrenergic blocking, antioxidant, and/or α-adrenergic blocking action. Rabbits with heart failure induced by rapid cardiac pacing were randomized to receive subcutaneous carvedilol, metoprolol, propranolol plus doxazosin, or placebo pellets for 8 wk and compared with sham-operated rabbits without pacing. We found rapid cardiac pacing produced clinical heart failure, left ventricular dilation, and decline of left ventricular fractional shortening. This was associated with an increase in left ventricular end-diastolic pressure, decrease in left ventricular first derivative of left ventricular pressure, and myocyte hypertrophy. Tissue oxidative stress measured by GSH/GSSG was increased in the heart with increased oxidation product of mitochondrial DNA, 8-oxo-7,8-dihydro-2′-deoxyguanosine, increase of Bax, decrease of Bcl-2, and increase of apoptotic myocytes as measured by anti-single-stranded DNA monoclonal antibody. Administration of carvedilol and metoprolol, which had no effect in sham animals, attenuated cardiac ventricular remodeling, cardiac hypertrophy, oxidative stress, and myocyte apoptosis in CHF. In contrast, propranolol plus doxazosin, which has less antioxidant effects, produced smaller effects on left ventricular function and myocyte apoptosis. In all animals, GSH/GSSG correlated significantly with changes of left ventricular end-diastolic dimension ( r = −0.678, P < 0.0001), fractional shortening ( r = 0.706, P < 0.0001), and apoptotic myocytes ( r = −0.473, P = 0.0001). Thus our findings suggest antioxidant and antiapoptotic actions of carvedilol and metoprolol are important determinants of clinical beneficial effects of β-receptors in the treatment of CHF.


Heart ◽  
2014 ◽  
Vol 100 (11) ◽  
pp. 819-820
Author(s):  
Matthias Dewenter ◽  
Christiane Vettel ◽  
Ali El-Armouche

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Grzegorz Gielerak ◽  
Paweł Krzesiński ◽  
Ewa Piotrowicz ◽  
Ryszard Piotrowicz

Aim. Cardiac rehabilitation (CR) is an important part of heart failure (HF) treatment. The aim of this paper was to evaluate if thoracic fluid content (TFC) measured by impedance cardiography (ICG) is a useful parameter for predicting the outcome of CR.Methods. Fifty HF patients underwent clinical and noninvasive haemodynamic (TFC) assessments before and after 8-week CR.Results. As a result of CR, the patients’ exercise tolerance improved, especially in terms of peak VO2(18.7 versus 20.8 mL × kg−1× min−1;P=0.025). TFC was found to identify patients with significantly improved peak VO2after CR. “High TFC” patients (TFC > 27.0 kOhm−1), compared to those of “low TFC” (TFC < 27.0 kOhm−1), were found to have more pronounced increase in peak VO2(1.3 versus 3.1 mL × kg−1× min−1;P=0.011) and decrease in TFC (4.0 versus 0.7 kOhm−1;P<0.00001). On the other hand, the patients with improved peak VO2(n=32) differed from those with no peak VO2improvement in terms of higher baseline TFC values (28.4 versus 25.3 kOhm−1;P=0.039) and its significant decrease after CR (2.7 versus 0.2 kOhm−1;P=0.012).Conclusions. TFC can be a useful parameter for predicting beneficial effects of CR worth including in the process of patients’ qualification for CR.


2021 ◽  
Vol 10 (Supplement_1) ◽  
Author(s):  
M Ribeiro Da Silva ◽  
G Santos Silva ◽  
D Caeiro ◽  
M Passos Silva ◽  
C Guerreiro ◽  
...  

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Cardiorenal syndrome (CRS) is common in patients with acute heart failure (AHF) and is associated with poor prognosis. Levosimendan (LVS) is an inodilator used in AHF and has beneficial effects on renal function (RF). However, its effects on RF in CRS patients are not established. Purpose To evaluate whether LVS could improve RF in AHF patients with or without CRS. Methods Retrospective study that included patients with AHF treated with LVS in a cardiac intensive care unit of a tertiary center, between January 2015 and June 2018. Baseline serum creatinine (SCr) was recorded and SCr and glomerular filtration rate (GFR) were accessed before and within 5 days after LSV use. CRS was defined as an increase in SCr &gt; 0,3 mg/dL over baseline (before LVS use). RF improvement was defined as a decrease in SCr after LVS use. We evaluate outcomes at 1-year. Results 61 patients were included, 84% males, mean age 65 years, ejection fraction ≤40% in 87%. INTERMACS 4 and hemodynamic profile C were the most frequent presentation. LSV was administered in 24h, without bolus, in most patients. CRS was present in 44,3% of patients. Basal characteristics were similar between CRS and no-CRS patients, including prevalence of chronic kidney disease, baseline SCr or natriuretic peptides (p&gt; 0,05 for all). CRS patients had a significant improvement in RF after LVS use (SCr 2,08 to 1,65 mg/dL, p&lt; 0,001 and GFR 40,4 to 54,6 mL/min/m2, p&lt; 0,001), while no-CRS patients had no significant improvement in RF (SCr 1,33 to 1,32 mg/dL and GFR 64,1 to 64,5 mL/min/m2, p&gt; 0,05 for all). Also, there was a significant decrease in natriuretic peptides after LVS in CRS patients (NT-proBNP 13527,5 to 10708,8 pg/mL, p= 0,006), without significant differences in no-CRS patients. It is noteworthy that at discharge, CRS patients were more likely to titrate HF optimal medical therapy (OMT) compared with no-CRS patients (p= 0,039). There was a lower tendency to suspend angiotensin-converting enzyme (ACE-I) and angiotensin receptor blockers (ARB) in CRS patients (p= 0,05). At discharge CRS patients received more furosemide than at admission (77,2 mg/day to 97,1 mg/day, p= 0,019) compared with no-CRS patients (89,6 mg/day to 97,0 mg/day, p= 0,469), receiving similar doses at discharge. In CRS patients, RF improvement was associated with a decrease in intra-hospital mortality (p= 0,043) and a tendency to decrease 30-day mortality (p= 0,060), but without differences in one-year mortality. Conclusion In CRS patients, LVS improved RF and NT-proBNP, allowed to titrate OMT and decreased the need to suspend ACE-I or ARB and was associated to a decrease in short-term mortality.


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