Hypertension-induced remodeling of cardiac excitation-contraction coupling in ventricular myocytes occurs prior to hypertrophy development

2007 ◽  
Vol 293 (6) ◽  
pp. H3301-H3310 ◽  
Author(s):  
Ye Chen-Izu ◽  
Ling Chen ◽  
Tamás Bányász ◽  
Stacey L. McCulle ◽  
Byron Norton ◽  
...  
Keyword(s):  
Cardiac Output ◽  
Heart Disease ◽  
Action Potential ◽  
Cardiac Hypertrophy ◽  
Ventricular Myocytes ◽  
Myocardial Contraction ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Window Period ◽  
Coupling System

Hypertension is a major risk factor for developing cardiac hypertrophy and heart failure. Previous studies show that hypertrophied and failing hearts display alterations in excitation-contraction (E-C) coupling. However, it is unclear whether remodeling of the E-C coupling system occurs before or after heart disease development. We hypothesized that hypertension might cause changes in the E-C coupling system that, in turn, induce hypertrophy. Here we tested this hypothesis by utilizing the progressive development of hypertensive heart disease in the spontaneously hypertensive rat (SHR) to identify a window period when SHR had just developed hypertension but had not yet developed hypertrophy. We found the following major changes in cardiac E-C coupling during this window period. 1) Using echocardiography and hemodynamics measurements, we found a decrease of left ventricular ejection fraction and cardiac output after the onset of hypertension. 2) Studies in isolated ventricular myocytes showed that myocardial contraction was also enhanced at the same time. 3) The action potential became prolonged. 4) The E-C coupling gain was increased. 5) The systolic Ca2+ transient was augmented. These data show that profound changes in E-C coupling already occur at the onset of hypertension and precede hypertrophy development. Prolonged action potential and increased E-C coupling gain synergistically increase the Ca2+ transient. Functionally, augmented Ca2+ transient causes enhancement of myocardial contraction that can partially compensate for the greater workload to maintain cardiac output. The increased Ca2+ signaling cascade as a molecular mechanism linking hypertension to cardiac hypertrophy development is also discussed.

Changes in ionic currents and β-adrenergic receptor signaling in hypertrophied myocytes overexpressing Gαq

2000 ◽  
Vol 279 (1) ◽  
pp. H139-H148 ◽  
Author(s):  
Sayaka Mitarai ◽  
Thomas D. Reed ◽  
Atsuko Yatani
Keyword(s):  
Action Potential ◽  
Cardiac Hypertrophy ◽  
Adrenergic Receptor ◽  
Myocardial Function ◽  
Ventricular Myocytes ◽  
Ionic Currents ◽  
Left Ventricular ◽  
Inward Rectifier ◽  
Maximal Response ◽  
Maximal Increase

Transgenic overexpression of Gαq causes cardiac hypertrophy and depressed contractile responses to β-adrenergic receptor agonists. The electrophysiological basis of the altered myocardial function was examined in left ventricular myocytes isolated from transgenic (Gαq) mice. Action potential duration was significantly prolonged in Gαq compared with nontransgenic (NTG) myocytes. The densities of inward rectifier K+ currents, transient outward K+ currents ( I to), and Na+/Ca2+ exchange currents were reduced in Gαq myocytes. Consistent with functional measurements, Na+/Ca2+ exchanger gene expression was reduced in Gαq hearts. Kinetics or sensitivity of I to to 4-aminopyridine was unchanged, but 4-aminopyridine prolonged the action potential more in Gαq myocytes. Isoproterenol increased L-type Ca2+ currents ( I Ca) in both groups, with a similar EC50, but the maximal response in Gαq myocytes was ∼24% of that in NTG myocytes. In NTG myocytes, the maximal increase of I Ca with isoproterenol or forskolin was similar. In Gαq myocytes, forskolin was more effective and enhanced I Ca up to ∼55% of that in NTG myocytes. These results indicate that the changes in ionic currents and multiple defects in the β-adrenergic receptor/Ca2+ channel signaling pathway contribute to altered ventricular function in this model of cardiac hypertrophy.

Vergleich von Belastungs- EKG und Radionuklid- Ventrikulographie bezüglich des Nachweises einer Myokardischämie bei isolierten Stenosen des Ramus interventricularis anterior

1988 ◽  
Vol 27 (02) ◽  
pp. 57-62
Author(s):  
R. Standke ◽  
R. P. Baum ◽  
S. Tezak ◽  
D. Mildenberger ◽  
F. D. Maul ◽  
...  
Keyword(s):  
Heart Disease ◽  
Left Ventricular Ejection Fraction ◽  
Myocardial Ischemia ◽  
Ejection Fraction ◽  
Anterior Wall ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Global Ejection Fraction ◽  
Ventricular Ejection Fraction ◽  
Exercise Ecg

21 patients with LAD-stenoses of at least 70% and 21 patients with LAD- stenoses and additional intramural anterior wall infarctions were studied. 20 patients without heart disease or after successful transluminal coronary angioplasty and 18 patients with intramural anterior wall infarction after successful transluminal dilatation of the LAD (remaining stenosis maximal 30%) served as controls. The normal range of global and regional left ventricular ejection fraction response to exercise was defined based on the data of 25 further patients without relevant coronary heart disease. Thus, a decrease in global ejection fraction and regional wall motion abnormalities were judged pathological. All patients were comparable with respect to age, ejection fraction at rest and work load. Myocardial ischemia could be detected by the exercise ECG in 81 % of all patients without infarction and in 71 % of patients with infarction. The corresponding values for global left ventricular ejection fraction were 76% and 81 %, respectively, and for regional ejection fraction 95% in both groups. No false-positive exercise ECGs were observed in the healthy controls and 2 (11 %) in the corresponding group with intramural infarction. The global ejection fraction was pathological in 1 (5%) healthy subject without infarction and in 3 (17%) corresponding patients with infarction. Sectorial analysis revealed 5 and 22%, respectively. Our findings suggest that the exercise ECG has a limited sensitivity to detect myocardial ischemia in patients with isolated LAD-stenoses and intramural myocardial infarction. Radionuclide ventriculography yields pathological values more often; however, false-positive results also occur more frequently.

Glutamine Is Cardioprotective in Patients with Ischemic Heart Disease following Cardiopulmonary Bypass

2011 ◽  
Vol 14 (6) ◽  
pp. 384 ◽  
Author(s):  
Vladimir V. Lomivorotov ◽  
Sergey M. Efremov ◽  
Vladimir A. Shmirev ◽  
Dmitry N. Ponomarev ◽  
Vladimir N. Lomivorotov ◽  
...  
Keyword(s):  
Heart Disease ◽  
Placebo Group ◽  
Cardiopulmonary Bypass ◽  
Ischemic Heart Disease ◽  
Troponin I ◽  
Left Ventricular ◽  
Ischemic Heart ◽  
Left Ventricular Ejection ◽  
Study Group ◽  
Cardioprotective Effects

<p><b>Background:</b> The aim of the present study was to investigate the cardioprotective effects of the perioperative use of N(2)-L-alanyl-L-glutamine (GLN) in patients with ischemic heart disease (IHD) who undergo their operations under cardiopulmonary bypass (CPB).</p><p><b>Methods:</b> This double-blind, placebo-controlled, randomized study included 50 patients who underwent cardiac surgery with CPB. Exclusion criteria were a left ventricular ejection fraction <50%, diabetes mellitus, <3 months since the onset of myocardial infarction, and emergency surgery. Patients in the study group (n = 25) received 0.4 g/kg GLN (Dipeptiven, 20% solution) per day. Patients in the control group (n = 25) were administered a placebo (0.9% NaCl). The primary end point was the dynamics of troponin I at the following stages: (1) prior to anesthesia, (2) 30 minutes after CPB, (3) 6 hours after CPB, (4) 24 hours after surgery, and (5) 48 hours after surgery. Secondary end points included measurements of hemodynamics with a Swan-Ganz catheter.</p><p><b>Results:</b> On the first postoperative day after the surgery, the median troponin I level was significantly lower in the study group than in the placebo group: 1.280 ng/mL (interquartile range [IQR], 0.840-2.230 ng/mL) versus 2.410 ng/mL (IQR, 1.060-6.600 ng/mL) (<i>P</i> = .035). At 4 hours after cardiopulmonary bypass (CPB), the median cardiac index was higher in the patients in the study group: 2.58 L/min per m<sup>2</sup> (IQR, 2.34-2.91 L/min per m<sup>2</sup>) versus 2.03 L/min per m<sup>2</sup> (IQR, 1.76-2.32 L/min per m<sup>2</sup>) (<i>P</i> = .002). The median stroke index also was higher in the patients who received GLN: 32.8 mL/m<sup>2</sup> (IQR, 27.8-36.0 mL/m<sup>2</sup>) versus 26.1 mL/m<sup>2</sup> (IQR, 22.6-31.8 mL/m<sup>2</sup>) (<i>P</i> = .023). The median systemic vascular resistance index was significantly lower in the study group than in the placebo group: 1942 dyn�s/cm<sup>5</sup> per m<sup>2</sup> (IQR, 1828-2209 dyn�s/cm<sup>5</sup> per m<sup>2</sup>) versus 2456 dyn�s/cm<sup>5</sup> per m<sup>2</sup> (IQR, 2400-3265 dyn�s/cm<sup>5</sup> per m<sup>2</sup>) (<i>P</i> = .001).</p><p><b>Conclusion:</b> Perioperative administration of GLN during the first 24 hours has cardioprotective effects in IHD patients following CPB. This technique enhances the troponin concentration at 24 hours after surgery and is associated with improved myocardial function.</p>

PULMONARY VASCULAR RESISTANCE BY ECHOCARDIOGRAPHY-DOPPLER IN ISCHEMIC HEART DISEASE WITH LEFT VENTRCULAR SYSTOLIC DYSFUNCTION

2017 ◽  
pp. 89-94
Author(s):  
Ke Toan Tran ◽  
Thi Thuy Hang Nguyen
Keyword(s):  
Heart Disease ◽  
Ischemic Heart Disease ◽  
Pulmonary Vascular Resistance ◽  
Vascular Resistance ◽  
Tricuspid Valve ◽  
Left Ventricular ◽  
Ischemic Heart ◽  
Left Ventricular Ejection ◽  
S Wave ◽  
Echocardiography Doppler

Objective: To determine pulmonary vascular resistance (PVR) by echocardiography - Doppler and to find correlation between pulmonary vascular resistance with left ventricular EF, PAPs, TAPSE, tissue S-wave of the tricuspid valve in patients with ischemic heart disease. Subjects and Methods: We studied on 82 patients with ischemic heart disease and EF<40% including 36 females, 46 males. Patients were estimated for pulmonary vascular resistance, EF, PAPs, TAPSE, tissue S-wave of the tricuspid valve by echocardiographyDoppler. Results: 64.6% of patients are increased PVR, average of PVR is 3.91 ± 1.85 Wood units and it is increasing with NYHA severity. There are negative correlations between pulmonary vascular resistance with left ventricular ejection fraction (r = - 0.545; p <0.001), TAPSE index (r= -0.590; p <0.001) and tissue S-wave of the tricuspid valve (r = -0.420; p <0.001); positive correlation with systolic pulmonary artery pressure (r = 0.361, p = 0.001), Conclusions: Increased PVR is the primary mechanism for pulmonary hypertension and right heart failure in patients with left heart disease. Determination of PVR in patients with left ventricular dysfunction by echocardiography is important in clinical practice. Key words: Echocardiography-Doppler; Pulmonary vascular resistance; ischemic heart disease

Sex differences in pharmacotherapy and long-term outcomes in patients with ischaemic heart disease and left ventricular dysfunction

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Dagan ◽  
D Dinh ◽  
J Stehli ◽  
C Tan ◽  
A Brennan ◽  
...  
Keyword(s):  
Heart Disease ◽  
Ischaemic Heart Disease ◽  
Medical Therapy ◽  
Left Ventricular Dysfunction ◽  
Ventricular Dysfunction ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Kaplan Meier ◽  
Long Term Mortality

Abstract Background Left ventricular dysfunction and ischaemic heart disease are common amongst women, however, women tend to present later and are less likely to receive guideline-directed medical therapy compared to their male counterparts. Purpose To investigate if a sex discrepancy exists for optimal medical therapy (OMT) and long-term mortality in a cohort of patients with known ischaemic heart disease (IHD) and left ventricular dysfunction. Methods We analysed prospectively collected data from a multicentre registry database collected between 2005–2018 on pharmacotherapy 30-days post percutaneous coronary intervention (PCI) in 13,015 patients with left ventricular ejection fraction (LVEF) &lt;50%. OMT at 30-days was defined as beta-blocker (BB), angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEi/ARB) ± mineralocorticoid receptor antagonist (MRA). Long-term mortality was determined by linkage with the National Death Index, with median follow up of 4.7 (IQR 2.0–8.6) years. Results Mean age was 65±12 years; women represented 20.2% (2,634) of the cohort. Women were on average 5 years older, had higher average BMI, higher rates of hypertension, diabetes, renal dysfunction, prior stroke and rheumatoid arthritis. Men were more likely to have sleep apnoea, be current/ex-smokers and to have had prior myocardial infarction, PCI and bypass surgery. Overall, 72.3% (9,411) of patients were on OMT, which was similar between sexes (72.7% in women vs. 72.2% in men, p=0.58). Rates of BB therapy were similar between sexes (85.2% vs. 84.5%, p=0.38), while women were less likely to be on an ACEi/ARB (80.4% vs. 82.4%, p=0.02) and more likely to be on a MRA (12.1% vs. 10.0%, p=0.003). Amongst those with LVEF ≤35% (n=1,652), BB (88.7% vs. 87.3%, p=0.46), ACEi/ARB (83.3% vs. 82.1%, p=0.59) and MRA use (32.5% vs. 33.3%, p=0.78) was comparable. Aspirin use was similar between sexes (95.3% vs. 95.9%, p=0.12), while women were less likely to be on statin therapy (93.5% vs. 95.3%, p&lt;0.001) and a second antiplatelet agent (94.4% vs. 95.6%, p=0.007). On unadjusted analysis women had significantly higher long-term mortality of 25.4% compared to 19.0% for men (p&lt;0.001). Kaplan-Meier analysis out to 14 years demonstrated that men on OMT have the best long-term survival overall and women on sub-OMT have significantly poorer outcomes compared to men on sub-OMT. However, after adjusting for OMT and other comorbidities there was no difference in long-term mortality between sexes (HR 0.99, 95% CI 0.87–1.14, p=0.94). Conclusion From this large multicentre registry, we found similar rates of guideline-directed pharmacotherapy for left ventricular dysfunction between sexes, however women were less likely to be on appropriate IHD secondary prevention. The increased unadjusted long-term mortality amongst women is likely due to differing baseline risk, given that adjusted mortality was similar between sexes. Kaplan-Meier Survival Analysis Funding Acknowledgement Type of funding source: None

scholarly journals Major Left Bundle Branch Block and Coronary Heart Disease—Are There Any Differences between the Sexes?

2021 ◽  
Vol 10 (11) ◽  
pp. 2284
Author(s):  
Diana Gurzău ◽  
Alexandra Dădârlat-Pop ◽  
Bogdan Caloian ◽  
Gabriel Cismaru ◽  
Horaţiu Comşa ◽  
...  
Keyword(s):  
Risk Factors ◽  
Heart Disease ◽  
Ischemic Heart Disease ◽  
Left Bundle Branch Block ◽  
Left Ventricular ◽  
Ischemic Heart ◽  
Left Ventricular Ejection ◽  
Bundle Branch Block ◽  
Microvascular Angina ◽  
Ventricular Ejection Fraction

Left bundle branch block is not a benign pathology, and its presence requires the identification of a pathological substrate, such as ischemic heart disease. Left bundle branch block appears to be more commonly associated with normal coronary arteries, especially in women. The objectives of our study were to describe the particularities of left bundle branch block in women compared to men with ischemic heart disease. Result: We included seventy patients with left bundle branch block and ischemic heart disease, with a mean age of 67.01 ± 8.89 years. There were no differences in the profile of risk factors, except for smoking and uric acid. The ventricular depolarization (QRS) duration was longer in men than women (136.86 ± 8.32 vs. 132.57 ± 9.19 msec; p = 0.018) and also men were observed to have larger left ventricular diameters. Left bundle branch block duration was directly associated with ventricular diameters and indirectly associated with left ventricular ejection fraction value, especially in women (R = −0.52, p = 0.0012 vs. R = −0.50, p = 0.002). In angiography, 80% of women had normal epicardial arteries compared with 65.7% of men; all these patients presented with microvascular dysfunction. Conclusion: The differences between the sexes were not so obvious in terms of the presence of risk factors; instead, there were differences in electrocardiographic, echocardiographic, and angiographic aspects. Left bundle branch block appears to be a marker of microvascular angina and systolic dysfunction, especially in women.

Extracting and analyzing ejection fraction values from electronic echocardiography reports in a large health maintenance organization

2016 ◽  
Vol 23 (4) ◽  
pp. 319-328 ◽  
Author(s):  
Fagen Xie ◽  
Chengyi Zheng ◽  
Albert Yuh-Jer Shen ◽  
Wansu Chen
Keyword(s):  
Heart Disease ◽  
Ejection Fraction ◽  
Health Maintenance Organization ◽  
Prognostic Indicator ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Free Text ◽  
Ventricular Ejection Fraction ◽  
Health Maintenance ◽  
Systolic Left Ventricular Function

The left ventricular ejection fraction value is an important prognostic indicator of cardiovascular outcomes including morbidity and mortality and is often used clinically to indicate severity of heart disease. However, it is usually reported in free-text echocardiography reports. We developed and validated a computerized algorithm to extract ejection fraction values from echocardiography reports and applied the algorithm to a large volume of unstructured echocardiography reports between 1995 and 2011 in a large health maintenance organization. A total of 621,856 echocardiography reports with a description of ejection fraction values or systolic functions were identified, of which 70 percent contained numeric ejection fraction values and the rest (30%) were text descriptions explicitly indicating the systolic left ventricular function. The 12.1 percent (16.0% for male and 8.4% for female) of these extracted ejection fraction values are <45 percent. Validation conducted based on a random sample of 200 reports yielded 95.0 percent sensitivity and 96.9 percent positive predictive value.

The Assessment of Left Ventricular Ejection Fraction in Patients with Ischaemic Heart Disease by Contrast Ventriculography and Nuclear Angiography

1977 ◽  
Vol 53 (1) ◽  
pp. 55-61 ◽  
Author(s):  
A. L. Muir ◽  
W. J. Hannan ◽  
H. M. Brash ◽  
V. Baldwa ◽  
H. C. Miller ◽  
...  
Keyword(s):  
Heart Disease ◽  
Left Ventricular Ejection Fraction ◽  
Ejection Fraction ◽  
Ischaemic Heart Disease ◽  
Ventricular Volume ◽  
Left Ventricular ◽  
Ventricular Ejection ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
Contrast Ventriculography

1. In 18 patients with ischaemic heart disease left ventricular ejection fraction, measured by two different nuclear angiographic methods, has been compared with ejection fraction measured by single-plane contrast angiography. 2. The first nuclear angiographic technique involves detection of variation in the radioactivity from the left ventricle during the initial passage of a bolus of 99Tcm-labelled human serum albumin injected intravenously; the second is our own modification of a ‘gated’ method, which accumulates the radioactivity detected during the continuing recirculation of the plasma bound radioisotope, so presenting an ‘averaged’ ventricular volume curve. 3. Ejection fraction, measured by the ‘bolus’ method, is lower than that measured either by contrast ventriculography or by the ‘gated’ method. This may be due to a damping effect. 4. Ejection fraction measured by the ‘gated’ method is well correlated with that measured by contrast ventriculography (r = 0·89). 5. Our modification of the ‘gated’ method, which presents the changes in ventricular volume throughout the cardiac cycle, without needing computer facilities, is a useful non-invasive means for assessment of left ventricular function.

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