scholarly journals Sex-related differences of early cardiac functional and proteomic alterations in a rat model of myocardial ischemia

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Bálint András Barta ◽  
Mihály Ruppert ◽  
Klemens Erwin Fröhlich ◽  
Miguel Cosenza-Contreras ◽  
Attila Oláh ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Diastolic Function ◽  
Inflammatory Responses ◽  
Systolic Dysfunction ◽  
Injection Pressure ◽  
Premenopausal Women ◽  
Bioinformatic Analysis ◽  
Left Ventricular ◽  
Mitochondrial Proteins ◽  
Matricellular Proteins

Abstract Background Reduced cardiovascular risk in premenopausal women has been the focus of research in recent decades. Previous hypothesis-driven experiments have highlighted the role of sex hormones on distinct inflammatory responses, mitochondrial proteins, extracellular remodeling and estrogen-mediated cardioprotective signaling pathways related to post-ischemic recovery, which were associated with better cardiac functional outcomes in females. We aimed to investigate the early, sex-specific functional and proteomic changes following myocardial ischemia in an unbiased approach. Methods Ischemia was induced in male (M-Isch) and female (F-Isch) rats with sc. injection of isoproterenol (85 mg/kg) daily for 2 days, while controls (M-Co, F-Co) received sc. saline solution. At 48 h after the first injection pressure–volume analysis was carried out to assess left ventricular function. FFPE tissue slides were scanned and analyzed digitally, while myocardial proteins were quantified by liquid chromatography–tandem mass spectrometry (LC–MS/MS) using isobaric labeling. Concentrations of circulating steroid hormones were measured with LC–MS/MS. Feature selection (PLS and PLS-DA) was used to examine associations among functional, proteomic and hormonal datasets. Results Induction of ischemia resulted in 38% vs 17% mortality in M-Isch and F-Isch respectively. The extent of ischemic damage to surviving rats was comparable between the sexes. Systolic dysfunction was more pronounced in males, while females developed a more severe impairment of diastolic function. 2224 proteins were quantified, with 520 showing sex-specific differential regulation. Our analysis identified transcriptional, cytoskeletal, contractile, and mitochondrial proteins, molecular chaperones and the extracellular matrix as sources of disparity between the sexes. Bioinformatics highlighted possible associations of estrogens and their metabolites with early functional and proteomic alterations. Conclusions Our study has highlighted sex-specific alterations in systolic and diastolic function shortly after ischemia, and provided a comprehensive look at the underlying proteomic changes and the influence of estrogens and their metabolites. According to our bioinformatic analysis, inflammatory, mitochondrial, chaperone, cytoskeletal, extracellular and matricellular proteins are major sources of intersex disparity, and may be promising targets for early sex-specific pharmacologic interventions. Graphical Abstract

Abstract 13910: Importance of Non-invasive Estimates of Left Ventricular Filling Pressures in Critically Ill Patients

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Abdelrahman M Ahmed ◽  
Brandon Wiley ◽  
Jacob C Jentzer ◽  
Nandan S Anavekar ◽  
Allan S Jaffe
Keyword(s):  
Diastolic Dysfunction ◽  
Diastolic Function ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Troponin T ◽  
Systolic Dysfunction ◽  
Left Ventricular ◽  
Adverse Outcomes ◽  
Icu Mortality ◽  
Lv Diastolic Function

Introduction: The presence of cardiac dysfunction predicts adverse outcomes in the intensive care unit (ICU). We explored the relationship of cardiac injury and left ventricular (LV) systolic and diastolic dysfunction (LVDD) to outcomes in critically ill patients. Methods: This is a retrospective analysis of adult medical ICU admissions from May, 2018 through October 2019. Patients with elevated high-sensitivity troponin T (hs-cTnT) and an echocardiogram performed within 72 hours of admission were included. Patients were classified as having normal LV diastolic function, isolated LVDD, concomitant LV diastolic and systolic dysfunction (LVDDSD) or indeterminate LV diastolic function based on American Society of Echocardiography 2016 guidelines. LV systolic dysfunction was defined as an ejection fraction (EF) < 50%. Results: Overall, 222 patients were included. LVDD was seen in 123 patients (55.4%). Thirty patients (13.5%) were classified with indeterminate diastolic function and 56 normal diastolic function (25.2%). Of those with LVDD , 59.3% had LVDDSD while isolated LVDD was seen in 40.7%.Patients with LVDDSD had a higher median hs-cTnT at baseline compared to patients with isolated LVDD [102ng/L IQR (50-257) vs. 77 ng/L (33.5-166); p=0.047]. Medial e’ velocity and tricuspid valve systolic regurgitant velocity were often associated with LV systolic dysfunction (p=0.0172 and 0.0013, respectively). LVDDSD was associated with a longer length of stay than patients with isolated LVDD [2.9 (1.6-4.0) vs.1.8 (1.1-3.3); p-value 0.03].Twenty-nine patients died during their ICU stay (13%). Patients with LVDDSD had 9.6-fold higher odds of dying in the ICU than patients with isolated LVDD (p=0.0048). Reduced medial e’ velocity (OR 0.63, CI 0.4-1.0, p=0.0285) and increased E/e’ (OR 1.08, CI 1.01-1.15, p=0.0192) were associated with ICU mortality. The association between LVEF<50% and ICU mortality was less pronounced (OR 0.95, CI 0.01-0.98; p=0.0023). Conclusions: Concomitant LV systolic and diastolic dysfunction and measures of increased cardiac filling pressures are strong predictors of mortality.

scholarly journals Effects of Ivabradine on Residual Myocardial Ischemia after PCI Evaluated by Stress Echocardiography

2019 ◽  
Vol 2019 ◽  
pp. 1-7 ◽  
Author(s):  
Simone Calcagno ◽  
Fabio Infusino ◽  
Olga Dettori ◽  
Temistocle Taccheri ◽  
Pasqualina Bruno ◽  
...  
Keyword(s):  
Diastolic Function ◽  
Stress Echocardiography ◽  
Left Ventricular Systolic Dysfunction ◽  
Systolic Dysfunction ◽  
Left Ventricular ◽  
Peak Exercise ◽  
Ventricular Systolic Dysfunction ◽  
Ejection Time ◽  
Double Product ◽  
Exercise Time

Background. Residual angina after PCI is a frequently occurring disease. Ivabradine improves symptoms but its role in patients without left ventricular systolic dysfunction is still unclear. The aim was to quantify the effects of ivabradine in terms of MVO2 indicators and diastolic function. Methods. Twenty-eight consecutive patients with residual angina after PCI were randomized to ivabradine 5 mg twice/day (IG) or standard therapy (CG). All patients performed a stress echocardiography at the enrollment and after 30 days. MVO2 was estimated from double product (DP) and triple product (TP) integrating DP with ejection time (ET). Diastolic function was evaluated determining E and A waves, E′ measurements, and E/E′ ratio both at rest and at the peak of exercise. Results. The exercise time was longer in IG 9′49″ ± 48″ vs 8′09″ ± 59″ in CG (p=0.0001), reaching a greater workload (IG 139.3 ± 13.4 vs CG 118.7 ± 19.6 Watts; p=0.003). MVO2 expressed with DP and TP was significantly higher in IG (DP: IG 24194 ± 2697 vs CG 20358 ± 4671.8, p=0.01; TP: IG 17239 ± 4710 vs CG 12206 ± 4413, p=0.007). At peak exercise, the ET was diminished in IG than CG. The analysis of diastolic function after the exercise revealed an increase of E and A waves, without difference in the E/A ratio. The E′ wave was higher in IG than CG, and in the same group, the differences between baseline and peak exercise were greater (∆E′3.14 ± 0.7 vs 2.4 ± 1.13, p=0.047). The E/E′ ratio was reduced in patients treated with ivabradine (IG 10.2 ± 2.0 vs CG 7.9 ± 1.6, p=0.002). Conclusions. Ivabradine seems to produce a significant improvement of ischemic threshold, chronotropic reserve, and diastolic function.

scholarly journals Nrf2 Deficiency Unmasks the Significance of Nitric Oxide Synthase Activity for Cardioprotection

2018 ◽  
Vol 2018 ◽  
pp. 1-15 ◽  
Author(s):  
Ralf Erkens ◽  
Tatsiana Suvorava ◽  
Thomas R. Sutton ◽  
Bernadette O. Fernandez ◽  
Monika Mikus-Lelinska ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Infarct Size ◽  
De Novo ◽  
Ischemia Reperfusion Injury ◽  
Systolic Function ◽  
Ischemia Reperfusion ◽  
Systolic Dysfunction ◽  
Left Ventricular ◽  
Early Reperfusion ◽  
Myocardial Ischemia Reperfusion

The transcription factor nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a key master switch that controls the expression of antioxidant and cytoprotective enzymes, including enzymes catalyzing glutathione de novo synthesis. In this study, we aimed to analyze whether Nrf2 deficiency influences antioxidative capacity, redox state, NO metabolites, and outcome of myocardial ischemia reperfusion (I/R) injury. In Nrf2 knockout (Nrf2 KO) mice, we found elevated eNOS expression and preserved NO metabolite concentrations in the aorta and heart as compared to wild types (WT). Unexpectedly, Nrf2 KO mice have a smaller infarct size following myocardial ischemia/reperfusion injury than WT mice and show fully preserved left ventricular systolic function. Inhibition of NO synthesis at onset of ischemia and during early reperfusion increased myocardial damage and systolic dysfunction in Nrf2 KO mice, but not in WT mice. Consistent with this, infarct size and diastolic function were unaffected in eNOS knockout (eNOS KO) mice after ischemia/reperfusion. Taken together, these data suggest that eNOS upregulation under conditions of decreased antioxidant capacity might play an important role in cardioprotection against I/R. Due to the redundancy in cytoprotective mechanisms, this fundamental antioxidant property of eNOS is not evident upon acute NOS inhibition in WT mice or in eNOS KO mice until Nrf2-related signaling is abrogated.

Left ventricular systolic dysfunction precedes diastolic dysfunction during myocardial ischemia in conscious dogs

1994 ◽  
Vol 267 (1) ◽  
pp. H333-H343 ◽  
Author(s):  
T. Ihara ◽  
K. Komamura ◽  
Y. T. Shen ◽  
T. A. Patrick ◽  
I. Mirsky ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Diastolic Dysfunction ◽  
Left Ventricular Systolic Dysfunction ◽  
Systolic Dysfunction ◽  
Left Ventricular ◽  
Conscious Dogs ◽  
Lv Function ◽  
Wall Thickening ◽  
Left Main ◽  
Isovolumic Relaxation

We studied the initial effects of regional and global left ventricular (LV) ischemia induced by left circumflex and left main coronary artery occlusion (CAO), respectively, on indexes of systolic and diastolic LV function in conscious dogs to determine whether diastolic abnormalities precede systolic dysfunction or vice versa during the onset of either regional or global myocardial ischemia. With regional myocardial ischemia, within four beats after left circumflex CAO, there was a significant decrease in end-systolic wall thickness in the ischemic zone followed by significantly enhanced postsystolic wall thickening in the nonischemic zone at beat 6. Both peak negative first derivative of left ventricular pressure (LV dP/dt) and the isovolumic relaxation half-time (T 1/2) were prolonged, but later (i.e., by the 9th beat). During sustained CAO T1/2 was normalized shortly after postsystolic thickening in the nonischemic zone had disappeared despite persistent regional systolic asynchrony and shortened ejection time. Thus postsystolic thickening in the nonischemic zone played a major role in the early, transient changes in isovolumic relaxation after acute induction of regional ischemia. With global myocardial ischemia, induced by left main coronary occlusion, indexes of systolic function (e.g., LV dP/dt, ejection fraction, and velocity of circumferential endocardial fiber shortening) were also depressed significantly before (by 5–15 beats) indexes of LV diastolic function [e.g., time constant of isovolumic relaxation and LV myocardial and chamber stiffness (by 35–45 beats)]. Similar results were observed in the presence of autonomic blockade, when heart rate did not change with CAO. Thus, during the induction of either acute regional or acute global LV ischemia in conscious dogs, LV systolic dysfunction occurs before diastolic dysfunction.

scholarly journals Peripartum Cardiomyopathy Presenting with Predominant Left Ventricular Diastolic Dysfunction: Efficacy of Bromocriptine

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Piercarlo Ballo ◽  
Irene Betti ◽  
Giuseppe Mangialavori ◽  
Leandro Chiodi ◽  
Gherardo Rapisardi ◽  
...  
Keyword(s):  
Heart Failure ◽  
Diastolic Dysfunction ◽  
Diastolic Function ◽  
Systolic Function ◽  
Systolic Dysfunction ◽  
Left Ventricular ◽  
Peripartum Cardiomyopathy ◽  
Lv Function ◽  
Lv Diastolic Dysfunction ◽  
Lv Diastolic Function

Management of patients with peripartum cardiomyopathy (PPCM) is still a major clinical problem, as only half of them or slightly more show complete recovery of left ventricular (LV) function despite conventional evidence-based treatment for heart failure. Recent observations suggested that bromocriptine might favor recovery of LV systolic function in patients with PPCM. However, no evidence exists regarding its effect on LV diastolic dysfunction, which is commonly observed in these patients. Tissue Doppler (TD) is an echocardiographic technique that provides unique information on LV diastolic performance. We report the case of a 37-year-old white woman with heart failure (NYHA class II), moderate LV systolic dysfunction (ejection fraction 35%), and severe LV diastolic dysfunction secondary to PPCM, who showed no improvement after 2 weeks of treatment with ramipril, bisoprolol, and furosemide. At 6-week followup after addition of bromocriptine, despite persistence of LV systolic dysfunction, normalization of LV diastolic function was shown by TD, together with improvement in functional status (NYHA I). At 18-month followup, the improvement in LV diastolic function was maintained, and normalization of systolic function was observed. This paper might support the clinical utility of bromocriptine in patients with PPCM by suggesting a potential benefit on LV diastolic dysfunction.

scholarly journals P1508 Left ventricular diastolic function plays a different role on mortality depending on the severity of systolic dysfunction in acute heart failure patients with reduced ejection fraction

2020 ◽  
Vol 21 (Supplement_1) ◽  
Author(s):  
K Nakamura ◽  
A Yamada ◽  
S Jinno ◽  
M Kato ◽  
A Takahashi ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Diastolic Function ◽  
Acute Heart Failure ◽  
Cardiac Death ◽  
Systolic Dysfunction ◽  
Left Ventricular ◽  
Group Iii ◽  
Group I ◽  
Lv Diastolic Function

Abstract Background It remains to be clarified whether clinical significance of left ventricular (LV) diastolic function differs depending on the severity of LV systolic dysfunction in patients with acute heart failure (AHF). The aim of this study was to examine the prognostic role of LV diastolic function in AHF patients with various systolic dysfunction.Methods: We studied consecutive hospitalized AHF patients with LV ejection fraction (LVEF) &lt;50%. The exclusion criteria were as follows: atrial fibrillation, severe mitral regurgitation, and inadequate echo image quality. They underwent echocardiography on admission. The eligible patients (n = 289, 165 males, 76 ± 10 years) were divided into 4 groups based on LVEF and left atrial pressure (LAP) grade estimated as in the ESC guidelines: Group I (LVEF 40-49% (mildly reduced LVEF)/normal LAP, n = 28), II (mildly reduced EF/increased LAP, n = 38), III (LVEF &lt;40% (severely reduced LVEF)/normal LAP, n = 110), and IV (severely reduced LVEF/increased LAP, n = 113). Cardiac death was examined up to 60 months.Results: In total, 58 patients (20%) died because of cardiac events during the follow-up (mean 20 ± 19 months). In patients with mildly reduced LVEF, Group I showed significantly less cardiac death ratio than II (n = 1 vs 10, Group I vs II, p = 0.03). On the other hand, in patients with severely reduced LVEF, there was no significant difference in cardiac death ratio between Group III and IV (n = 23 vs 24, Group III vs IV, p = 0.80). That is, LAP grade was a prognostic marker when the patients had mild LV systolic dysfunction, whereas it did not contribute to the prediction of cardiac mortality when patients showed severely reduced LV systolic function. Group I showed significantly better prognosis than those with severe LV systolic dysfunction regardless of LAP grade (Group III, IV) (Group I vs III, p = 0.04; Group I vs IV, p = 0.04).Conclusions: LV diastolic function may have a different clinical significance depending on the severity of LV systolic dysfunction in AHF patients.

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