Abstract 18342: Inducible Cardiomyocyte-Specific Deletion of Stromal Interaction Molecules Results in Cardiomyopathy in Mice

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Saravanakumar Murugesan ◽  
Ryan D Sullivan ◽  
Salvatore Mancarella
Keyword(s):  
Heart Rate ◽  
Dilated Cardiomyopathy ◽  
Mammalian Cells ◽  
Calcium Release ◽  
Cardiac Contractility ◽  
Calcium Transient ◽  
Left Ventricular ◽  
P Wave ◽  
Calcium Sensors

Background: Stromal interaction molecules (STIM1 and STIM2) are sarco/endoplasmic calcium sensors ubiquitously expressed in mammalian cells. Upon Ca2+ store discharge STIM proteins oligomerize in proximity of the plasma membrane to activate the Ca2+ selective channels (Orai) and trigger Ca2+ entry. While this mechanism is widely accepted to be the main source of calcium in non-excitable cells, in cardiomyocytes the calcium-induced calcium-release is the major controller of myocardial function, and the presence of STIM in these cells appears somewhat puzzling. Here we investigated the role of STIM in cardiomyocytes and its role in regulating cardiac contractility and intracellular Ca2+ dynamics. Methods: We have generated an inducible cardiac-specific STIM1 knockout (STIM KO) mouse model to elucidate the role of STIM in the myocardium. Echocardiography was used to evaluate structure and function of the left ventricle. Heart rate was monitored continuously in conscious mice by telemetry. Cell dimensions, shortening, and relaxation were determined by videomicroscopy and calcium transients by fura 2. Results: Echocardiographic analyses revealed development of dilated cardiomyopathy with a significant reduction of left ventricular fractional shortening (39.91±4.05% vs. 22.41±7.92%, p<0.01). Histological and morphological analyses confirmed a dilated cardiomyopathy characterized by enlarged ventricular chambers. Electrocardiography showed higher heart rate in the STIM1 KO mice with no differences in P-wave duration and QRS interval while Q-T interval was reduced in the STIM1 KO mice as compared to the WT mice. Sarcomere length and cell shortening measurements in freshly isolated cardiomyocytes from STIM1 KO mice confirmed the reduced contractility associated with a reduction of time to 50% relaxation (283±13ms vs. 258±8ms, p<0.05) . Intracellular calcium transient analysis in STIM1 KO cardiomyocytes showed a higher peak amplitude and a time to 50% decay of calcium significantly accelerated. Conclusions: Our data demonstrate that STIM proteins play an important role in the maintaining normal cardiac function in the adult heart and reveal that STIM plays an important role during cardiac repolarization.

Deletion of peroxisome proliferator-activated receptor-α induces an alteration of cardiac functions

2006 ◽  
Vol 291 (1) ◽  
pp. H161-H166 ◽  
Author(s):  
Cécile Loichot ◽  
Laurence Jesel ◽  
Angela Tesse ◽  
Antonia Tabernero ◽  
Kristina Schoonjans ◽  
...  
Keyword(s):  
Heart Rate ◽  
Myocardial Fibrosis ◽  
Ex Vivo ◽  
Left Ventricular ◽  
P Wave ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Intraventricular Conduction ◽  
Cardiac Functions

The peroxisome proliferator-activated receptor-α (PPARα) plays a major role in the control of cardiac energy metabolism. The role of PPARα on cardiac functions was evaluated by using PPARα knockout (PPARα −/−) mice. Hemodynamic parameters by sphygmomanometric measurements show that deletion of PPARα did not affect systolic blood pressure and heart rate. Echocardiographic measurements demonstrated reduced systolic performance as shown by the decrease of left ventricular fractional shortening in PPARα −/− mice. Telemetric electrocardiography revealed neither atrio- nor intraventricular conduction defects in PPARα −/− mice. Also, heart rate, P-wave duration and amplitude, and QT interval were not affected. However, the amplitude of T wave from PPARα −/− mice was lower compared with wild-type (PPARα +/+) mice. When the myocardial function was measured by ex vivo Langendorff's heart preparation, basal and β-adrenergic agonist-induced developed forces were significantly reduced in PPARα-null mice. In addition, Western blot analysis shows that the protein expression of β1-adrenergic receptor is reduced in hearts from PPARα −/− mice. Histological analysis showed that hearts from PPARα −/− but not PPARα +/+ mice displayed myocardial fibrosis. These results suggest that PPARα-null mice have an alteration of cardiac contractile performance under basal and under stimulation of β1-adrenergic receptors. These effects are associated with myocardial fibrosis. The data shed light on the role of PPARα in maintaining cardiac functions.

The role of inflammation in recent-onset dilated cardiomyopathy

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
A Chaloupka ◽  
J Krejci ◽  
H Poloczkova ◽  
P Hude ◽  
E Ozabalova ◽  
...  
Keyword(s):  
Dilated Cardiomyopathy ◽  
Left Ventricular ◽  
Pcr Analysis ◽  
Myocardial Inflammation ◽  
Gene Variants ◽  
Absolute Increase ◽  
Recent Onset ◽  
Cardiotropic Viruses

Abstract Background The aetiology of recent-onset dilated cardiomyopathy (RODCM) includes inflammatory, genetic, toxic and metabolic causes. Delineating the role of inflammation on the genetic background could improve risk stratification. Purpose We aimed to ascertain the role of inflammation evaluated by serum CRP immunohistochemical and PCR analysis of endomyocardial biopsy (EMB) in conjunction with genetic testing in left ventricular reverse remodelling (LVRR) in 12-month follow-up. Methods 83 RODCM patients enrolled in this prospective observational study underwent 12-month echocardiographic follow up whole-exome sequencing, and EMB. Presence of cardiotropic viruses was determined by PCR analysis of the EMB samples. Inflammation was defined according to TIMIC immunohistochemical criteria as the presence of &gt;7 CD3+ lymphocytes/mm2 and/or &gt;14 infiltrating leukocytes (LCA+ cells/mm2). LVRR was defined as an absolute increase in LV ejection fraction &gt; +10% and a relative decrease of LV end-diastolic diameter &gt;−10% at 12 months. Results LVRR occurred in 28 (34%) of all cases. PCR analysis uncovered cardiotropic viruses in 55 (66%) patients, with highest prevalence of parvovirus B19 (47%). (Figure 1) EMB analysis detected inflammation in 28 (34%) cases and inflammation significantly positively predicted LVRR (P=0.019). Sequencing identified disease-related gene variants (ACMG class 3–5) in 45 (54%) patients. Carriers of non-titin gene variants showed a lowest probability of 12-month LVRR (19%) P=0.041. Combination of genetic findings and inflammation did not improve the prediction of LVRR in 12 months. (Table 1) Conclusion Both myocardial inflammation and disease-causing variants can be identified in a large proportion of RODCM cases. Prognostic value of CRP and virus detection is low. Non-titin disease-related variants carriers of are less likely to reach LVRR. In contrast, myocardial inflammation detected by EMB predicts favourable remodelling in 12 months. Figure 1 Funding Acknowledgement Type of funding source: None

Electrocardiographic Predictors of Cognitive Decline and Dementia: A Systematic Review

2021 ◽  
pp. 1-20
Author(s):  
Yume Imahori ◽  
Davide L. Vetrano ◽  
Petter Ljungman ◽  
Chengxuan Qiu
Keyword(s):  
Systematic Review ◽  
Heart Rate ◽  
Cognitive Decline ◽  
Prospective Studies ◽  
Left Ventricular ◽  
Qt Prolongation ◽  
P Wave ◽  
Cross Sectional ◽  
Incident Dementia ◽  
Electrocardiogram Ecg

Background: Markers of altered cardiac function might predict cognitive decline and dementia. Objective: This systematic review aims to review the literature that examines the associations of various electrocardiogram (ECG) markers with cognitive decline and dementia in middle-aged and elderly populations. Methods: We searched PubMed, Embase, and Web of Science through 1 July 2020 for literature and conducted a systematic literature review. We included studies examining the associations of ECG markers (e.g., left ventricular hypertrophy [LVH], spatial QRS-T angle, and QT prolongation) with cognitive function and dementia in adult populations regardless of study setting and design, but excluded studies examining atrial fibrillation and heart rate variability. Results: Fourteen community-based cross-sectional and longitudinal studies were identified. ECG markers were investigated in association with dementia in four prospective studies, and with cognitive decline in ten prospective studies. ECG-assessed LVH was associated with dementia in one study while five heterogeneous prospective studies yielded inconsistent associations with cognitive decline. Regarding ventricular repolarization markers, spatial QRS-T angle was associated with cognitive decline in one study while another study found no association between QT prolongation and cognitive decline. High resting heart rate was associated with both dementia and cognitive decline in one study but not associated with dementia in another study. P-wave abnormality was significantly associated with incident dementia and cognitive decline in one prospective study. Conclusion: Some ECG markers were associated with incident dementia and cognitive decline. However, limited number of heterogeneous studies did not allow us to make firm conclusions. Further studies are needed.

scholarly journals The Role of Cardiac T-Cadherin in the Indicating Heart Failure Severity of Patients with Non-Ischemic Dilated Cardiomyopathy

Medicina ◽  
2020 ◽  
Vol 56 (1) ◽  
pp. 27
Author(s):  
Vaida Baltrūnienė ◽  
Ieva Rinkūnaitė ◽  
Julius Bogomolovas ◽  
Daiva Bironaitė ◽  
Ieva Kažukauskienė ◽  
...  
Keyword(s):  
Heart Failure ◽  
Dilated Cardiomyopathy ◽  
Experimental Studies ◽  
Left Ventricular ◽  
Human Myocardium ◽  
Enzyme Linked Immunosorbent Assay ◽  
Cox Regression Analysis ◽  
Non Ischemic Dilated Cardiomyopathy ◽  
The Mean

Background and objectives: T-cadherin (T-cad) is one of the adiponectin receptors abundantly expressed in the heart and blood vessels. Experimental studies show that T-cad sequesters adiponectin in cardiovascular tissues and is critical for adiponectin-mediated cardio-protection. However, there are no data connecting cardiac T-cad levels with human chronic heart failure (HF). The aim of this study was to assess whether myocardial T-cad concentration is associated with chronic HF severity and whether the T-cad levels in human heart tissue might predict outcomes in patients with non-ischemic dilated cardiomyopathy (NI-DCM). Materials and Methods: 29 patients with chronic NI-DCM and advanced HF were enrolled. Patients underwent regular laboratory investigations, echocardiography, coronary angiography, and right heart catheterization. TNF-α and IL6 in serum were detected by enzyme-linked immunosorbent assay (ELISA). Additionally, endomyocardial biopsies were obtained, and the levels of T-cad were assessed by ELISA and CD3, CD45Ro, CD68, and CD4- immunohistochemically. Mean pulmonary capillary wedge pressure (PCWP) was used as a marker of HF severity, subdividing patients into two groups: mean PCWP > 19 mmHg vs. mean PCWP < 19 mmHg. Patients were followed-up for 5 years. The study outcome was composite: left ventricular assist device implantation, heart transplantation, or death from cardiovascular causes. Results: T-cad shows an inverse correlation with the mean PCWP (rho = −0.397, p = 0.037). There is a tendency towards a lower T-cad concentration in patients with more severe HF, as indicated by the mean PCWP > 19 mmHg compared to those with mean PCWP ≤ 19 mmHg (p = 0.058). Cardiac T-cad levels correlate negatively with myocardial CD3 cell count (rho = −0.423, p = 0.028). Conclusions: Univariate Cox regression analysis did not prove T-cad to be an outcome predictor (HR = 1, p = 0.349). However, decreased T-cad levels in human myocardium can be an additional indicator of HF severity. T-cad in human myocardium has an anti-inflammatory role. More studies are needed to extend the role of T-cad in the outcome prediction of patients with NI-DCM.

Adrenal contribution to cardiac responses elicited by acute hypoxia in piglets

1980 ◽  
Vol 239 (6) ◽  
pp. H751-H755 ◽  
Author(s):  
J. C. Lee ◽  
J. C. Werner ◽  
S. E. Downing
Keyword(s):  
Heart Rate ◽  
Adrenal Glands ◽  
Acute Hypoxia ◽  
Cardiac Contractility ◽  
Sympathetic Nerves ◽  
Left Ventricular ◽  
Cardiac Work ◽  
Ganglionic Blockade ◽  
Cardiac Responses

The adrenal contribution to cardiac responses elicited by acute hypoxia was assessed in 16 piglets, 1-12 wks old, anesthetized with pentobarbital (30 mg/kg). External cardiac work was held constant and parasympathetic blockade was produced in each animal with atropine (1 mg). Hypoxia was produced by addition of N2 to the respirator. In a sham-adrenalectomy group (n = 6) left ventricular (LV) dP/dtmax increased significantly during hypoxia (PaO2 approximately 30 mmHg) to 3,680 +/- 414 mmHg/s from control values of 2,686 +/- 317 mmHg/s (P < 0.01). Heart rate rose from 171 +/- 6 to 186 +/- 7 beats/min (P < 0.02). These responses were not significantly altered by ganglionic blockade with trimethaphan camsylate (0.5 mg x kg-1 x min-1). Equally large increases of LV dP/dtmax appeared when heart rate was held constant by pacing. beta-Adrenoreceptor blockade with practolol (4 mg/kg) sharply reduced but did not eliminate the response. In contrast, no changes in LV dP/dtmax or heart rate were observed during hypoxia in adrenalectomized piglets (n = 6). These findings indicate that the increased cardiac contractility during acute hypoxia in piglets is dependent on the integrity of the adrenal glands and that there is minimal contribution from cardiac sympathetic nerves.

P370Added value changes in signal sonr in patients with = <30% left ventricular ejection fraction

EP Europace ◽  
2020 ◽  
Vol 22 (Supplement_1) ◽  
Author(s):  
J J Garcia Guerrero ◽  
J Fernandez De La Concha Castaneda ◽  
A Chacon Pinero ◽  
J Garcia Fernandez ◽  
I Fernandez Lozano ◽  
...  
Keyword(s):  
Ejection Fraction ◽  
Hospital Admission ◽  
Dilated Cardiomyopathy ◽  
Interim Analysis ◽  
Cardiac Contractility ◽  
Inverse Correlation ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
Lv Ejection Fraction

Abstract Abstract/Introduction Decompensated congestive heart failure (CHF) is a main and increasing health problem worldwide, which leads to patients’ bad outcomes and high money expenditure. Direct relationship between Brain Natriuretic Peptides (NT-proBNP) increasing levels and adverse clinical outcomes have been demonstrated in patients with CHF.  SonR signal sensor, a micro-accelerometer embedded in the tip of the atrial lead in patients implanted with devices, picks up cardiac muscle vibration. Its amplitude is a surrogate for cardiac contractility, which is found to be further reduced in patients with decompensated CHF. Purpose We sought to find a significant inverse correlation between SonR signal and NT-proBNP levels, in order to use SonR as a surrogate of NT-proBNP to anticipate worsening CHF leading to hospital admission. Methods AVCs SONR trial is a pilot, prospective, observational, multicentre study, in which patients with dilated cardiomyopathy, any aetiology, LV ejection fraction ≤ 30%, at least one recent (&lt; 1 year) hospital admission due to CHF, and implanted with CRT-D devices (used as dual-chamber, no left ventricular (LV) lead implanted) with SonR sensor feature, were enrolled. During a year, NT-proBNP and SonR values were obtained every month, and both levels compared (Pearson’s test) Results This an interim analysis of our data, 18 months after the first patient was enrolled. Twenty two patients and 116 data pairs were analysed. Most patients were men (91%) and had ischemic dilated cardiomyopathy (59%). Mean age was 61 (range 34-82) and mean LV ejection fraction was 27% (range 15-30). The mean Pearson’s correlation coefficient of the NT-proBNP values and the SonR signal was r = - 0.36 (95% CI -0.51 to -0.19), p &lt; 0.00006 (Figure) Conclusions The interim analysis of this study shows an inverse and very significant relationship between SonR signal and NT-proBNP values. This suggests SonR signal might be used as predictor of worsening CHF. Abstract Figure

scholarly journals Overexpression of A3 adenosine receptors decreases heart rate, preserves energetics, and protects ischemic hearts

2002 ◽  
Vol 283 (4) ◽  
pp. H1562-H1568 ◽  
Author(s):  
Heather R. Cross ◽  
Elizabeth Murphy ◽  
Richard G. Black ◽  
John Auchampach ◽  
Charles Steenbergen
Keyword(s):  
Heart Rate ◽  
Contractile Function ◽  
Ischemia Reperfusion ◽  
Specific Inhibitor ◽  
Left Ventricular ◽  
Atp Depletion ◽  
Wild Type ◽  
Basal Heart Rate ◽  
Developed Pressure

To determine whether A3 adenosine receptor (A3AR) signaling modulates myocardial function, energetics, and cardioprotection, hearts from wild-type and A3AR-overexpressor mice were subjected to 20-min ischemia and 40-min reperfusion while 31P NMR spectra were acquired. Basal heart rate and left ventricular developed pressure (LVDP) were lower in A3AR-overexpressor hearts than wild-type hearts. Ischemic ATP depletion was delayed and postischemic recoveries of contractile function, ATP, and phosphocreatine were greater in A3AR-hearts. To determine the role of depressed heart rate and to confirm A3AR-specific signaling, hearts were paced at 480 beats/min with or without 60 nmol/l MRS-1220 (A3AR-specific inhibitor) and then subjected to ischemia-reperfusion. LVDP was similar in paced A3AR-overexpressor and paced wild-type hearts. Differences in ischemic ATP depletion and postischemic contractile and energetic dysfunction remained in paced A3AR-overexpressor hearts versus paced wild-type hearts but were abolished by MRS-1220. In summary, A3AR overexpression decreased basal heart rate and contractility, preserved ischemic ATP, and decreased postischemic dysfunction. Pacing abolished the decreased contractility but not the ATP preservation or cardioprotection. Therefore, A3AR overexpression results in cardioprotection via a specific A3AR effect, possibly involving preservation of ATP during ischemia.

scholarly journals Hyperthyroidism-induced dilated cardiomyopathy

2019 ◽  
Vol 7 (27) ◽  
pp. 64-66 ◽  
Author(s):  
Phumpattra Chariyawong ◽  
Angela Rao ◽  
Deepa Panikkath ◽  
Ragesh Panikkath
Keyword(s):  
Heart Failure ◽  
Heart Rate ◽  
Dilated Cardiomyopathy ◽  
Systolic Function ◽  
Cardiac Contractility ◽  
Contributing Factors ◽  
Endocrine Disorder ◽  
Hyperdynamic State ◽  
History Of ◽  
High Output

Hyperthyroidism is a common endocrine disorder with a prevalence of 1.3% in the generalpopulation, affecting more women than men. Prolonged hyperthyroidism without appropriatemanagement may lead to high output cardiac failure characterized by increases in heart rate,cardiac contractility, and cardiac output and by reductions in peripheral systemic vascularresistance. Dilated cardiomyopathy with impaired systolic function is rare and occurs in lessthan 1% of patients with thyrotoxicosis. The exact mechanism of hyperthyroidism-induceddilated cardiomyopathy is not well established. The combination of direct toxic effects of excessthyroid hormone along with prolonged tachycardia, arrhythmia, and a hyperdynamic state couldbe contributing factors. We present a case of a young woman with prolonged sinus tachycardiadue to a long history of medication non-compliance who developed dilated cardiomyopathywith low output heart failure. Early detection and management of hyperthyroidism are crucialto restore cardiac function.

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