Lactobacillus plantarum Probiotic Induces Nrf2-mediated Antioxidant Signaling and eNOS Expression Resulting in Improvement of Myocardial Diastolic Function

2021 ◽  
Author(s):  
Ahmed Aboulgheit ◽  
Catherine Karbasiafshar ◽  
Zhiqi Zhang ◽  
Mohamed Sabra ◽  
Guangbin Shi ◽  
...  
Keyword(s):  
Myocardial Perfusion ◽  
Diastolic Function ◽  
Caffeic Acid ◽  
Left Ventricular ◽  
Ischemic Myocardium ◽  
Heme Oxygenase 1 ◽  
Vascular Density ◽  
Myocardial Tissue ◽  
Standard Diet ◽  
Enos Expression

Yorkshire swine were fed standard diet (n=7) or standard diet containing caffeic acid with L. plantarum (n=7) for three weeks. Next, an ameroid constrictor was placed around the left coronary circumflex artery, and the dietary regimens were continued. At fourteen weeks, cardiac function, myocardial perfusion, vascular density, and molecular signaling in ischemic myocardium were evaluated.The L. plantarum-caffeic acid augmented Nrf2 in the ischemic myocardium, and induced Nrf2-regulated antioxidant enzymes heme oxygenase-1 (HO-1), NADPH dehydrogenase quinone 1 (NQO-1), and thioredoxin reductase (TRXR-1). Improved left ventricular diastolic function and decreased myocardial collagen expression were seen in animals receiving the L. plantarum-caffeic acid supplements. The expression of endothelial nitric oxide synthase (eNOS) was increased in ischemic myocardial tissue of the treatment group, while levels of asymmetric dimethyl arginine (ADMA), hypoxia inducible factor 1α (HIF-1α), and phosphorylated MAPK (pMAPK) were decreased. Collateral dependent myocardial perfusion was unaffected while arteriolar and capillary densities were reduced as determined by a-smooth muscle cell actin and CD31 immunofluorescence in ischemic myocardial tissue. Dietary supplementation with L. plantarum and caffeic acid is a safe and effective method of enhancing Nrf2-mediated antioxidant signaling cascade in ischemic myocardium. Although this experimental diet was associated with a reduction in hypoxic stimuli, decreased vascular density and without any change in collateral-dependent perfusion, the net effect of an increase in antioxidant activity and eNOS expression resulted in improvement in diastolic function.

Abstract 16245: Lactobacillus Plantarum Probiotic Preserves Endothelial Function and Diastolic Performance in the Ischemic Myocardium Through Redox Nrf2 Antioxidant Signaling

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Ahmed M Aboulgheit ◽  
Zhiqi Zhang ◽  
guangbin shi ◽  
Catherine Karbasiafshar ◽  
Neel Sodha ◽  
...  
Keyword(s):  
Endothelial Function ◽  
Caffeic Acid ◽  
Lactobacillus Plantarum ◽  
Smooth Muscle Actin ◽  
Ischemic Myocardium ◽  
Vascular Density ◽  
Standard Diet ◽  
Alpha Smooth Muscle Actin ◽  
Circumflex Artery ◽  
Antioxidant Genes

Introduction: Oxidative homeostasis is critical to the viability of the vascular endothelium. Nrf2 is a redox-sensitive transcription factor that induces several cyto-protective and antioxidant genes in response to stress. Lactobacillus plantarum , a probiotic bacterium, can convert caffeic acid to 4-vinyl catechol, a natural activator of Nrf2. Hypothesis: We hypothesized that a diet consisting of applesauce, which is rich in caffeic acid, supplemented with L. plantarum can generate sufficient concentrations of 4-vinyl catechol to enhance Nrf2 activity and thereby ameliorate ischemic injury in the myocardium. Methods: Fourteen Yorkshire swine received a standard diet with 10 ml of 10% ethanol vehicle for three weeks (NDC; n=7); the treatment group was additionally fed unsweetened applesauce with L. plantarum supplements (ND-LP; n=7). Subsequently, an ameroid constrictor was placed around their left coronary circumflex artery (Lcx). Dietary regimens were continued for a period of fourteen weeks thereafter. Finally, cardiac function, myocardial perfusion, vascular density, and molecular signaling were examined. Results: The L. plantarum -applesauce diet upregulated Nrf2 signaling in the ischemic myocardium, thus inducing several antioxidant enzymes including heme oxygenase1 (HO-1), NADPH dehydrogenase quinone 1 (NQO-1), and thioredoxin reductase (TRXR-1). Reduced ischemic myocardial density of alpha smooth muscle actin (αSMA) and improved myocardial relaxation seen in the treatment cohort may reflect less ischemic fibrosis. Nrf2 activation increased expression of endothelial nitric oxide synthase (eNOS) and lowered concentrations of asymmetric dimethyl arginine (ADMA) in ischemic myocardial tissue, but did not significantly affect blood flow nor endothelial cell density. The expression of hypoxia inducible factor 1α (HIF-1α) and phosphorylated MAPK (pMAPK) was reduced in ischemic myocardial lysates from treatment animals. Conclusions: Dietary supplementation with L. plantarum and caffeic acid is a safe and effective mean of enhancing Nrf2 activity, which supported endothelial function and diastolic performance, while diminishing hypoxic stimulation of collateral vessel formation in the ischemic myocardium.

scholarly journals Preservation of Contractile Reserve and Diastolic Function by Inhibiting the NLRP3 Inflammasome with OLT1177® (Dapansutrile) in a Mouse Model of Severe Ischemic Cardiomyopathy Due to Non-Reperfused Anterior Wall Myocardial Infarction

Molecules ◽  
2021 ◽  
Vol 26 (12) ◽  
pp. 3534
Author(s):  
Joseph Aliaga ◽  
Aldo Bonaventura ◽  
Eleonora Mezzaroma ◽  
Yogesh Dhakal ◽  
Adolfo Gabriele Mauro ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Diastolic Function ◽  
Nlrp3 Inflammasome ◽  
Ischemic Cardiomyopathy ◽  
Left Ventricular ◽  
Control Group ◽  
Contractile Reserve ◽  
Standard Diet ◽  
Group 3 ◽  
Group 1

Interleukin-1β (IL-1β), a product of the NLRP3 inflammasome, modulates cardiac contractility and diastolic function. We proposed that OLT1177® (dapansutrile), a novel NLRP3 inhibitor, could preserve contractile reserve and diastolic function after myocardial infarction (MI). We used an experimental murine model of severe ischemic cardiomyopathy through the ligation of the left coronary artery without reperfusion, and after 7 days randomly assigned mice showing large anterior MI (>4 akinetic segments), increased left ventricular (LV) dimensions ([LVEDD] > 4.4 mm), and reduced function (LV ejection fraction <40%) to a diet that was enriched with OLT1177® admixed with the chow in the diet at 3.75 g/kg (Group 1 [n = 10]) or 7.5 g/kg (Group 2 [n = 9]), or a standard diet as the no-treatment control group (Group 3 [n = 10]) for 9 weeks. We measured the cardiac function and contractile reserve with an isoproterenol challenge, and the diastolic function with cardiac catheterization at 10 weeks following the MI surgery. When compared with the control (Group 3), the mice treated with OLT1177 (Group 1 and 2) showed significantly greater preservation of their contractile reserve (the percent increase in the left ventricular ejection fraction [LVEF] after the isoproterenol challenge was +33 ± 11% and +40 ± 6% vs. +9 ± 7% in the standard diet; p < 0.05 and p < 0.005 for Group 1 and 2, respectively) and of diastolic function measured as the lower left ventricular end-diastolic pressure (3.2 ± 0.5 mmHg or 4.5 ± 0.5 mmHg vs. 10.0 ± 1.6 mmHg; p < 0.005 and p < 0.009 respectively). No differences were noted between the resting LVEF of the MI groups. These effects were independent of the effects on the ventricular remodeling after MI. NLRP3 inflammasome inhibition with OLT1177® can preserve β-adrenergic responsiveness and prevent left ventricular diastolic dysfunction in a large non-reperfused anterior MI mouse model. OLT1177® could therefore be used to prevent the development of heart failure in patients with ischemic cardiomyopathy.

scholarly journals Radiofrequency transmyocardial revascularization in experiment

2002 ◽  
Vol 1 (3) ◽  
pp. 39-45
Author(s):  
A. I. Opherkin ◽  
S. V. Logvinov ◽  
Y. A. Pokushalov
Keyword(s):  
Myocardial Perfusion ◽  
Ischemic Myocardium ◽  
Needle Electrode ◽  
Vascular Density ◽  
Vascular Volume ◽  
Benchmark Analysis ◽  
Transmyocardial Revascularization

Conducted benchmark analysis of influence to mechanical punctures, transmyocardial radiofrequency influence and lazer radiating on myocardium. Study is conducted on 284 rats. Transmyocardial revascularization (ТМR) was executed with use intramuscular needle, Nd:YAG lazer, radiofrequency generator with needle electrode. Study of vascular density and myocardial perfusion was conducted through 1, 2, 4 and 8 weeks. Maximum increasing vascular density was observed on 4 week. In groups with radiofrequency TMR and Nd:YAG TMR specific vascular volume is enlarged in 5 once (26,9 ± 1,9% and 22,2 ± 1,7%, accordingly; Р < 0,05) in contrast with the checking group (4,9 ± 1,6%). In the group with mechanical ТМР specific vascular volume is enlarged small (6,1 ± 1,3%). Increasing an accumulation 99mTc-myoview in the group with radiofrequency TMR occurred on 8 week by comparing with the checking group, it has formed 2,82 ± 0,31% (Р < 0,05) and 1,68 ± 0,21% accordingly. Conclusion: Analysis of vascular density points to alike efficiency of lazer and radiofrequency transmyocardial revascularization. Radiofrequency ТМR causes an increasing vascular density and improvement myocardial perfusion in ischemic myocardium.

scholarly journals Myocardial perfusion and cardiac dimensions during extracorporeal membrane oxygenation–supported circulation in a porcine model of critical post-cardiotomy failure

Perfusion ◽  
2020 ◽  
Vol 35 (8) ◽  
pp. 763-771
Author(s):  
Atle Solholm ◽  
Pirjo-Riitta Salminen ◽  
Lodve Stangeland ◽  
Christian Arvei Moen ◽  
Arve Mongstad ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiopulmonary Bypass ◽  
Myocardial Perfusion ◽  
Extracorporeal Membrane Oxygenation ◽  
Left Ventricular ◽  
Circulatory Support ◽  
Myocardial Tissue ◽  
Membrane Oxygenation ◽  
Venoarterial Extracorporeal Membrane Oxygenation ◽  
Tissue Oedema

Introduction: Venoarterial extracorporeal membrane oxygenation is widely used as mechanical circulatory support for severe heart failure. A major concern with this treatment modality is left ventricular distension due to inability to overcome the afterload created by the extracorporeal membrane oxygenation circuit. The present porcine study evaluates coronary circulation, myocardial perfusion and ventricular distension during venoarterial extracorporeal membrane oxygenation. Methods: Ten anesthetized open-chest pigs were cannulated and put on cardiopulmonary bypass. Heart failure was achieved by 90 minutes of aortic cross-clamping with insufficient cardioplegic protection. After declamping, the animals were supported by venoarterial extracorporeal membrane oxygenation for 3 hours. Continuous haemodynamic measurements were performed at baseline, during cardiopulmonary bypass/aortic cross-clamping and during venoarterial extracorporeal membrane oxygenation. Fluorescent microsphere injections at baseline and after 1, 2 and 3 hours on venoarterial extracorporeal membrane oxygenation evaluated myocardial perfusion. Left ventricular function and distension were assessed by epicardial echocardiography. Results: The myocardial injury caused by 90 minutes of ischaemia resulted in a poorly contracting myocardium, necessitating venoarterial extracorporeal membrane oxygenation in all animals. The circulatory support maintained the mean arterial blood pressure within a satisfactory range. A hyperaemic left anterior descending coronary artery flow while on extracorporeal membrane oxygenation was observed compared to baseline. Myocardial tissue perfusion measured by microspheres was low, especially in the subendocardium. Echocardiography revealed myocardial tissue oedema, a virtually empty left ventricle, and a left ventricular output that remained negligible throughout the extracorporeal membrane oxygenation run. Conclusion: Coronary artery blood flow is maintained during venoarterial extracorporeal membrane oxygenation after cardiopulmonary bypass and cardioplegic arrest despite severely affected performance of the left ventricle. Myocardial perfusion decreases, however, presumably due to rapid development of myocardial tissue oedema.

scholarly journals Long-term obesity promotes alterations in diastolic function induced by reduction of phospholamban phosphorylation at serine-16 without affecting calcium handling

2014 ◽  
Vol 117 (6) ◽  
pp. 669-678 ◽  
Author(s):  
Ana Paula Lima-Leopoldo ◽  
André S. Leopoldo ◽  
Danielle C. T. da Silva ◽  
André F. do Nascimento ◽  
Dijon H. S. de Campos ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Diastolic Function ◽  
Posterior Wall ◽  
Left Ventricular ◽  
Calcium Handling ◽  
Standard Diet ◽  
Shortening Velocity

Few studies have evaluated the relationship between the duration of obesity, cardiac function, and the proteins involved in myocardial calcium (Ca2+) handling. We hypothesized that long-term obesity promotes cardiac dysfunction due to a reduction of expression and/or phosphorylation of myocardial Ca2+-handling proteins. Thirty-day-old male Wistar rats were distributed into two groups ( n = 10 each): control (C; standard diet) and obese (Ob; high-fat diet) for 30 wk. Morphological and histological analyses were assessed. Left ventricular cardiac function was assessed in vivo by echocardiographic evaluation and in vitro by papillary muscle. Cardiac protein expression of sarcoplasmic reticulum (SR) Ca2+-ATPase (SERCA2a), calsequestrin, L-type Ca2+ channel, and phospholamban (PLB), as well as PLB serine-16 phosphorylation (pPLB Ser16) and PLB threonine-17 phosphorylation (pPLB Thr17) were determined by Western blot. The adiposity index was higher (82%) in Ob rats than in C rats. Obesity promoted cardiac hypertrophy without alterations in interstitial collagen levels. Ob rats had increased endocardial and midwall fractional shortening, posterior wall shortening velocity, and A-wave compared with C rats. Cardiac index, early-to-late diastolic mitral inflow ratio, and isovolumetric relaxation time were lower in Ob than in C. The Ob muscles developed similar baseline data and myocardial responsiveness to increased extracellular Ca2+. Obesity caused a reduction in cardiac pPLB Ser16 and the pPLB Ser16/PLB ratio in Ob rats. Long-term obesity promotes alterations in diastolic function, most likely due to the reduction of pPLB Ser16, but does not impair the myocardial Ca2+ entry and recapture to SR.

scholarly journals Cardiac perfusion, structure, and function in type 2 diabetes mellitus with and without diabetic complications

2019 ◽  
Vol 21 (8) ◽  
pp. 887-895 ◽  
Author(s):  
Martin Heyn Sørensen ◽  
Annemie Stege Bojer ◽  
David Andrew Broadbent ◽  
Sven Plein ◽  
Per Lav Madsen ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Myocardial Perfusion ◽  
Diastolic Function ◽  
Diabetic Complications ◽  
Left Ventricular ◽  
Control Subjects ◽  
Lv Mass

Abstract Aims Coronary microvascular disease (CMD) is a known complication in type 2 diabetes mellitus (T2DM). We examined the relationship between diabetic complications, left ventricular (LV) function and structure and myocardial perfusion reserve (MPR) as indicators of CMD in patients with T2DM and control subjects. Methods and results This was a cross-sectional study of 193 patients with T2DM and 25 controls subjects. Patients were grouped as uncomplicated diabetes (n = 71) and diabetes with complications (albuminuria, retinopathy, and autonomic neuropathy). LV structure, function, adenosine stress, and rest myocardial perfusion were evaluated by cardiovascular magnetic resonance. Echocardiography was used to evaluate diastolic function. Patients with uncomplicated T2DM did not have significantly different LV mass and E/e* but decreased MPR (3.8 ± 1.0 vs. 5.1 ± 1.5, P &lt; 0.05) compared with controls. T2DM patients with albuminuria and retinopathy had decreased MPR (albuminuria: 2.4 ± 0.9 and retinopathy 2.6 ± 0.7 vs. 3.8 ± 1.0, P &lt; 0.05 for both) compared with uncomplicated T2DM patients, along with significantly higher LV mass (149 ± 39 and 147 ± 40 vs. 126 ± 33 g, P &lt; 0.05) and E/e* (8.3 ± 2.8 and 8.1 ± 2.2 vs. 7.0 ± 2.5, P &lt; 0.05). When entered in a multiple regression model, reduced MPR was associated with increasing E/e* and albuminuria and retinopathy were associated with reduced MPR. Conclusions Patients with uncomplicated T2DM have reduced MPR compared with control subjects, despite equivalent LV mass and E/e*. T2DM patients with albuminuria or retinopathy have reduced MPR and increased LV mass and E/e* compared with patients with uncomplicated T2DM. E/e* and MPR are significantly associated after adjustment for age, hypertension, and LV mass, suggesting a link between CMD and cardiac diastolic function. Clinical trial registration https://www.clinicaltrials.org. Unique identifier: NCT02684331

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