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.

Abstract 2488: Correlation Between The Severity Of Diastolic Dysfunction And Cardiac Torsion

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Sung-Ji Park ◽  
Chinami Miyazaki ◽  
Charles J Bruce ◽  
Diego Bellavia ◽  
Fletcher A Miller ◽  
...  
Keyword(s):  
Diastolic Dysfunction ◽  
Early Stage ◽  
Mitral Annulus ◽  
Left Ventricular ◽  
Control Group ◽  
Compensatory Mechanism ◽  
Diastolic Velocity ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

Backgrounds: Left ventricular torsion (LVtor) is an integral part of systole and untwisting plays an important role in diastole. The aim of this study was to characterize LVtor and untwisting in different grades of diastolic dysfunction. Methods: We studied 135 patients with normal LV EF with various grades of diastolic dysfunction (40 group1:mild,42 group 2:moderate,and 22 group 3:severe dysfunction) and 31 controls with normal diastolic function. Apical and basal short axis rotations were measured by 2D STE. LVtor was defined as net difference between apical and basal rotation. Results: Age, gender, and EF were similar in 3 groups and control. Mitral annulus early diastolic velocity was reduced in all 3 groups (see table ). Peak LVtor was significantly greater in group 1 compared with control, group 2 and group 3. The time from peak LVtor to Mitral valve opening, and to peak early diastolic velocity were significantly delayed in group 1 compared to control (p=0.0030 and 0.0409, respectively). The twisting rate and untwisting rate were found to be highest in group 1. Conclusions: Systolic torsion and diastolic untwisting are significantly increased in patients with mild diastolic dysfunction. In patients with advanced diastolic dysfunction with increased filling pressure, torsion and untwisting are normalized. Hence, vigorous LV torsion appears to be a compensatory mechanism during an early stage of diastolic dysfunction to maintain normal filling in the setting of reduced longitudinal myocardial motion.

Effects of isoproterenol on myocardial relaxation rate: influence of the level of load

1993 ◽  
Vol 265 (5) ◽  
pp. H1645-H1653 ◽  
Author(s):  
N. Coudray ◽  
J. P. Beregi ◽  
Y. Lecarpentier ◽  
D. Chemla
Keyword(s):  
Relaxation Rate ◽  
Muscle Length ◽  
Dose Dependence ◽  
Left Ventricular ◽  
Control Group ◽  
Shortening Velocity ◽  
Myocardial Relaxation ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

The present work was undertaken to test the hypothesis that the level of the load faced by the myocardium influences the effects of isoproterenol on relaxation rate. Responses to cumulative doses of isoproterenol (from 10(-10) to 10(-6) M) were studied in rat left ventricular papillary muscle stimulated 12 beats/min at 29 degrees C in 0.5 mM extracellular calcium and preloaded at initial muscle length corresponding to apex of length-active tension curve (Lmax; group 1, n = 20) or at 95% of Lmax (group 2, n = 9). A control group (group 3, n = 8) was studied every 15 min for 75 min. We measured maximum unloaded shortening velocity (Vmax), normalized positive and negative peak force derivatives (+dF and -dF, respectively) of the fully isometric twitch, and peak lengthening velocity of the isotonic twitch with preload only (Vlmax). In group 1, Vmax and +dF increased under 10(-10) and 10(-9) M isoproterenol, respectively, and -dF increased under 10(-9) M isoproterenol (115 +/- 13 vs. 96 +/- 12 mN.s-1.mm-2, P = 0.01). Conversely, Vlmax increased under 10(-7) M isoproterenol only (2.34 +/- 0.19 vs. 1.45 +/- 0.18 Lmax/s, P < 0.001). In group 2, both -dF and Vlmax increased under 10(-7) M isoproterenol only (P = 0.015 and 0.011, respectively). In group 3, -dF and Vlmax did not vary in time. Our results suggest a load-revealed (or length-revealed) difference in the dose dependence of the various biochemical processes involved in the effects of isoproterenol during myocardial relaxation.

Abstract 4206: Microvascular Dysfunction and Left Ventricular Chamber Stiffness after Successful Percutaneous Coronary Intervention Critically Determine Left Ventricular Remodeling in Patients with Acute Myocardial Infarction

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Atsushi Yamamuro ◽  
Takashi Akasaka ◽  
Shuichiro Kaji ◽  
Koichi Tamita ◽  
Minako Katayama ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Microvascular Dysfunction ◽  
Coronary Intervention ◽  
Left Ventricular ◽  
Percutaneous Coronary ◽  
Lv Remodeling ◽  
Group 3 ◽  
Group 1 ◽  
Deceleration Time

In patients with acute myocardial infarction (AMI), the short deceleration time of left ventricular (LV) early filling by Doppler is a powerful independent predictor of LV remodeling. On the other hand, recent studies have shown that microvascular dysfunction in recanalized infarct-related coronary arteries may predict progressive LV dilation. The purpose of this study was to examine the effects of both microvascular dysfunction and LV chamber stiffness on LV remodeling after successful percutaneous coronary intervention (PCI) in AMI patients. Two hundred and one consecutive patients with first anterior AMI were studied following successful PCI. Microvascular injury was evaluated on the basis of coronary flow velocity patterns immediately after successful PCI using Doppler guidewires. We defined the presence of microvascular dysfunction as diastolic deceleration time ≤600 ms and the presence of systolic flow reversal. LV filling patterns were determined by mitral inflow pulsed-wave Doppler examination on day 3 after AMI. Deceleration time ≤130 ms was defined as restrictive. We classified the patients into three categories: without restrictive and microvascular dysfunction (group 1, n=116), with restrictive or microvascular dysfunction (group 2, n= 38), and with restrictive and microvascular dysfunction (group 3, n=47). Left ventriculograms were obtained immediately and 6 months after PCI. LV remodeling was defined as an increase in end-diastolic volume index ≥20%. Group 3 was at the highest risk of LV remodeling, while group 1 was at the lowest (Table ). Assessment of both microvascular dysfunction and LV chamber stiffness enable accurate prediction of LV remodeling in AMI patients after successful PCI. LV remodeling in each group

Cardioprotective potential of chronopharmacotherapy in patients with arterial hypertension who had a transient ischemic attack

Kardiologiia ◽  
2021 ◽  
Vol 61 (11) ◽  
pp. 33-41
Author(s):  
S. V. Opolskaya ◽  
V. V. Skibitsky ◽  
A. V. Fendrikova ◽  
T. B. Zabolotskich ◽  
A. V. Skibitsky .
Keyword(s):  
Arterial Hypertension ◽  
Flow Velocity ◽  
Diastolic Function ◽  
Transient Ischemic Attack ◽  
Left Ventricular ◽  
Number Of Patients ◽  
Group 3 ◽  
Group 2 ◽  
Ischemic Attack ◽  
Group 1

Aim    Analysis of the cardioprotective effectivity of chronopharmacotherapy in patients with arterial hypertension (AH) after transient ischemic attack (TIA).Material and methods    174 patients with AH and TIA were evaluated. All patients were randomized to three groups based on the dosing schedule of chronopharmacotherapy: group 1 (n=59), patients receiving indapamide retard 1.5 mg and valsartan 160 mg, both in the morning; group 2 (n=58), indapamide retard 1.5 mg in the morning and valsartan 160 mg in the evening; group 3 (n=57), indapamide retard 1.5 mg in the morning and valsartan 80 mg in the morning and evening. Echocardiography (EchoCG) (ALOKA SSD 2500, Japan) was performed for all patients at baseline and at 12 months of the treatment. Statistical analysis of results was performed with the Statistica 12.0 (StatSoftInc, USA) software.Results    Before the treatment, EchoCG parameters did not significantly differ between the patient groups. After 12 months of the treatment, positive changes in the end-systolic dimension (ESD), interventricular septal thickness (IVST), thickness of the left ventricular posterior wall (TLVPW), LV myocardial mass (LVMM), LVMM index (LVMMI), ejection fraction (EF), ratio of transmitral early peak flow velocity and late filling flow velocity (E/A), and isovolumetric velocity relaxation time (IVRT) were more pronounced in the group of sartan evening dosing (group 2) than in the group of sartan single morning dosing (group 1) (p<0.05). In group 3, the changes in ESD, IVST, TLVPW, LVMM, LVMMI, EF, E/A ratio, deceleration time (DT) of LV, and IVRT were significantly greater than those in group 1, whereas the dynamics of ESD, IVST, TLVPW, LVMM, LVMMI, E/A ratio, and DT were better in group 3 than in group 2 (p<0.05). In addition, a significantly greater number of patients with normalized LV geometry was registered in group 3 compared to groups 1 and 2 (p<0.05). The number of patients with normal LV diastolic function after the treatment was also significantly greater in group 3 than in group 1 (p<0.05) and comparable with group 2.Conclusion    The morning dosing of indapamide retard and the b.i.d. dosing of valsartan provided more pronounced beneficial changes in major EcoCG indexes and improvement of LV geometry and diastolic function than the sartan single dosing only in the morning or evening in combination with the diuretic.

scholarly journals Mildronate effectiveness in post-hospital rehabilitation of patients with myocardial infarction

2012 ◽  
Vol 11 (2) ◽  
pp. 57-61
Author(s):  
V. P. Mikhin ◽  
O. N. Koltsova
Keyword(s):  
Myocardial Infarction ◽  
Diastolic Function ◽  
Left Ventricular ◽  
Control Group ◽  
Type I ◽  
Type Ii ◽  
Pharmaceutical Therapy ◽  
Complex Therapy ◽  
Systolic And Diastolic Function ◽  
Hospital Rehabilitation

Aim. To study the effects of mildronate, as a component of complex therapy, on left ventricular (LV) systolic and diastolic function and exercise capacity (EC) in myocardial infarction (MI) patients undergoing post-hospital rehabilitation. Material and methods. This open, randomized study included 2 groups (50 men in each group; mean age 53,8±2,7 years): the control group (CG) and the main group (MG), which suffered MI in 4 weeks prior to the study inclusion (70% with Q-wave MI and 30% with transmural MI), and had stable post-infarction angina, Functional Class (FC) II, and ejection fraction (EF) >35%. In both groups, pharmaceutical therapy included metoprolol (75-150 mg/d), isosorbide mononitrate (40 mg/d), aspirin (100 mg/d), clopidogrel (75 mg/d), atorvastatin (20-40 mg/d), and enalapril (2,5-5 mg/d). The MG patients additionally received mildronate (1,5 g/d) for 3 months. The follow-up period was 1 year. EC was assessed using veloergometry (VEM) and 6-minute walk test (6MWT). LV systolic and diastolic function was assessed with the use of Doppler echocardiography. The following parameters were calculated: EF, DTE, LV isovolumetric relaxation time (IVRT), and enddiastolic pressure (EDP). Two types of diastolic dysfunction (DD) were defined: Type I (E/A <1; DTE >0,220 ms) and Type II (E/A >1,5; DTE <0,150 ms). Results. Mildronate therapy facilitated EC recovery, improved VEM threshold capacity, and increased 6MWT velocity and distance. In addition, mildronate improved LV systolic and diastolic function in both types of DD, by increasing EF and reducing EDP. In type I DD, E/A and IVRT increased, while DTE decreased. In Type II DD, the changes were also positive, but different: E/A decreased, while IVRT increased. Conclusion. Adding mildronate to the complex therapy of MI patients at the post-hospital rehabilitation stage facilitates EC improvement and benefits LV systolic and diastolic function.

Effect of overweight and obesity on the left ventricular systolic and diastolic functions in patients with acute myocardial infarction

2012 ◽  
Vol 35 (4) ◽  
pp. 229 ◽  
Author(s):  
Fatih Poyraz ◽  
Murat Turfan ◽  
Sinan A. Kocaman ◽  
Huseyin U. Yazici ◽  
Nihat Sen ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Diastolic Function ◽  
Systolic Function ◽  
Study Groups ◽  
Left Ventricular ◽  
Normal Weight ◽  
Overweight And Obesity ◽  
Weight Group ◽  
Normal Weight Group ◽  
Diastolic Functions

Purpose: The purpose of this study was to evaluate whether a association exits among overweight and obesity and left ventricular systolic and diastolic functions in patients admitted with first ST-elevation myocardial infarction (STEMI). Methods: The present study was performed on 451 consecutive patients diagnosed with first STEMI (376 men, 75 women; mean age 56.1±10.8 years). The patients were classified into three groups based on their body mass index (BMI) as normal weight (BMI < 25 kg/m2), overweight (BMI: 25-29.9 kg/m2) and obese (BMI > 30 kg/m2). Echocardiographic features were evaluated and compared among the three groups. Results: Mitral annulus E velocities were higher in obese individuals than normal weight group (p < 0.01). In contrast, mitral A velocities were lower (p =0.03); consequently, E\A and E'\A' ratios were lower (both p =0.01) in the obese group with respect to normal weight group. When the correction of entire variations existing among the groups were performed using multivariate linear regressions analyses, it turned out that BMI was independently associated with E/A (β= -0.19, p =0.044) and with E'/A' (β= -0.016, p=0.021). Ejection fraction, wall motion score index and myocardial S velocities were comparable among the study groups (p > 0.05). Conclusion: These results suggest that while obesity has no adverse effect on the left ventricular systolic function, it has unfavorable consequences on the left ventricular diastolic function in the patients with first STEMI. In contrast, no unfavorable effects of overweight on the left ventricular systolic and diastolic function were detected.

The Effects of the "XGTQ" Medicine in Treating Cirrhosis in Wistar Rats

2020 ◽  
Vol 06 ◽  
Author(s):  
Ngan Nguyen Hoang ◽  
Thang Duong Minh ◽  
Tuan Anh Hoang ◽  
Son Le Ngoc Bich ◽  
Duong Nguyen Huu ◽  
...  
Keyword(s):  
Wistar Rats ◽  
Reference Group ◽  
Control Group ◽  
Plain Water ◽  
Group 4 ◽  
White Rats ◽  
Collagen Accumulation ◽  
Activity Of Enzymes ◽  
Group 3 ◽  
Group 1

Objectives: Evaluate the effects of "XGTQ" in the treatment of cirrhosis induced by Carbon tetrachloride (CCL4) in combination with alcohol and high-fat diet on Wistar rats. Materials and methods: Cirrhosis on white rats was induced by subcutaneously injecting CC14 at an initial dose of 5,0ml/kg, followed by 1,2ml/kg once a week in 10 weeks. Then, fed with synthetic food, added 20% fat, and 0.05% cholesterol and iron oxalate. Rats were administered every day with plain water and 1 day with water mixed with 30% ethanol. The rats were randomly divided into 5 groups and given distilled water (group 1 and 2 or control group), silymarin (group 3 or reference group) or the "XGTQ" drug extract (group 4, 5) for 4 weeks. Collected blood for biochemical test and liver were dissected to evaluate weight, morphology and quantified 4-hydroxyproline to evaluate fibrosis and collagen accumulation. Results: In cirrhotic wistar rats, "XGTQ" drug at 19.6 g/kg/24h and 58.8 g/kg/24h showed the ability of reducing the activity of enzymes AST, ALT in the blood (p<0.01), increasing plasma albumin and decreasing prothrobin time (p<.05); improving physical condition, macroscopic and microscopic images of H&E-stained liver; decreasing the concentration of hydroxyproline in the liver and reducing the level of cirrhosis on the masson-stained templates. The effects of "XGTQ" increased with the dose, and was equivalent to silymarin at the dose of 70 mg/kg/24h. Conclusion: The extract of "XGTQ" drug is effective in treating cirrhosis in Wistar rats.

scholarly journals The outcome of patients with myocardial infarction with non-obstructive coronary arteries (MINOCA) and impaired kidney function: a 3-year observational study

2021 ◽  
Author(s):  
Malgorzata Zalewska-Adamiec ◽  
Jolanta Malyszko ◽  
Ewelina Grodzka ◽  
Lukasz Kuzma ◽  
Slawomir Dobrzycki ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Incidence Rate ◽  
Kidney Function ◽  
Coronary Arteries ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
Risk Of Death ◽  
Group 2 ◽  
Group 1

Abstract Background Myocardial infarction with nonobstructive coronary arteries (MINOCA) constitutes about 10% of the cases of acute coronary syndromes (ACS). It is a working diagnosis and requires further diagnostics to determine the cause of ACS. Methods In this study, 178 patients were initially diagnosed with MINOCA over a period of 3 years at the Department of Invasive Cardiology of the University Clinical Hospital in Białystok. The value of estimated glomerular filtration rate (eGFR) was calculated for all patients. The patients were divided into 2 groups depending on the value of eGFR: group 1—53 patients with impaired kidney function (eGFR < 60 mL/min/1.73 m2; 29.8%) and group 2—125 patients with normal kidney function (eGFR ≥ 60 mL/min/1.73 m2; 70.2%). Results In group 1, the mean age of patients was significantly higher than that of group 2 patients (77.40 vs 59.27; p < 0.0001). Group had more women than group 2 (73.58% vs 49.60%; p = 0.003). Group 1 patients had higher incidence rate of arterial hypertension (92.45% vs 60.80%; p < 0.0001) and diabetes (32.08% vs 9.60%; p = 0.0002) and smoked cigarettes (22.64% vs 40.80%; p = 0.020). Group 1 patients had higher incidence rate of pulmonary edema, cardiogenic shock, sudden cardiac arrest (13.21% vs 4.00%; p = 0.025), and pneumonia (22.64% vs 6.40%; p = 0.001). After the 37-month observation, the mortality rate of the patients with MINOCA was 16.85%. Among group two patients, more of them became deceased during hospitalization (7.55% vs 0.80%; p = 0.012), followed by after 1 year (26.42% vs 7.20%; p = 0.0004) and after 3 years (33.96% vs 9.6%; p < 0.0001). Multivariate analysis revealed that the factors increasing the risk of death in MINOCA are as follows: older age, low eGFR, higher creatinine concentration, low left ventricular ejection fraction, and ST elevation in ECG. Conclusion Impaired kidney function is diagnosed in every third patient with MINOCA. Early and late prognosis of patents with MINOCA and renal dysfunction is poor, and their 3-year mortality is comparable to patients with myocardial infarction with significant stenosis of the coronary arteries and impaired kidney function.

scholarly journals Hypertrophy of unaffected cardiomyocytes correlates with severity of cardiomyopathy in female patients with Fabry disease

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Cristina Chimenti ◽  
Romina Verardo ◽  
Andrea Frustaci
Keyword(s):  
Fabry Disease ◽  
Wall Thickness ◽  
Left Ventricular ◽  
Female Patients ◽  
Maximal Wall Thickness ◽  
Group 4 ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

Abstract Aim To investigate the contribution of unaffected cardiomyocytes in Fabry disease cardiomyopathy. Findings Left ventricular (LV) endomyocardial biopsies from twenty-four females (mean age 53 ± 11 ys) with Fabry disease cardiomyopathy were studied. Diagnosis of FD was based on the presence of pathogenic GLA mutation, Patients were divided in four groups according with LV maximal wall thickness (MWT): group 1 MWT ≤ 10.5 mm, group 2 MWT 10.5–15 mm, group 3 MWT 16–20 mm, group 4 MWT > 20 mm. At histology mosaic of affected and unaffected cardiomyocytes was documented. Unaffected myocytes’ size ranged from normal to severe hypertrophy. Hypertrophy of unaffected cardiomyocytes correlated with severity of MWT (p < 0.0001, Sperman r 0,95). Hypertrophy of unaffected myocytes appear to concur to progression and severity of FDCM. It is likely a paracrine role from neighboring affected myocytes.

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