Abstract 23: Immunosuppression with FTY720 Reverses Cardiac Dysfunction to Prevent Chronic Heart Failure in Mice that Survive Diet-induced Myocardial Infarction

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Fu Sang Luk ◽  
Roy Y Kim ◽  
Kang Li ◽  
Daniel Ching ◽  
Sunil Joshi ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Chronic Heart Failure ◽  
Cardiac Dysfunction ◽  
Coronary Atherosclerosis ◽  
Left Ventricular ◽  
Lv Function ◽  
Chow Diet ◽  
Type I ◽  
Gene Repair

We recently reported that immunosuppression with FTY720 improves cardiac function and extends longevity in the HypoE/SR-BI-/- mouse model of diet-induced coronary atherosclerosis and myocardial infarction (MI). In this study we tested whether FTY720 could also reverse cardiac dysfunction in mice that survive MI and subsequently develop chronic heart failure (CHF). HypoE/SR-BI-/- mice were bred to Mx1-Cre mice and offspring were fed a high fat diet (HFD) for 21 days to provoke hyperlipidemia, coronary atherosclerosis and recurrent MIs. HypoE/SR-BI-/-Mx1-Cre mice were subsequently given oral FTY720 in drinking water or not. Hyperlipidemia was permanently reversed by inducible Cre-mediated gene repair of the HypoE allele (also known as the Apoeh/h allele) that rapidly restores normal apoE expression in all tissues and by switching mice to a normal chow diet. In cohorts of mice that survived this period of HFD, left ventricular (LV) function was monitored using serial echocardiography for up to 15 weeks. In untreated mice, LV performance progressively deteriorated. Although FTY720 treatment did not initially prevent a decline of heart function among HypoE/SR-BI-/-Mx1-Cre mice six weeks after Cre-mediated gene repair, it almost completely restored normal LV function in these mice by 15 weeks after cessation of HFD. Reversal of heart failure did not result from reduced atherosclerosis as the burden of both aortic and coronary atherosclerosis increased to similar levels in both groups of mice. Rather, FTY720 caused systemic immunosuppression as assessed by reduced numbers of circulating T and B lymphocytes. In the heart, FTY720 led to reduced expression of MMP-2 along with the expression of genes involved in Type I innate inflammation that we have recently demonstrated as major contributors to heart failure. Our data demonstrate the benefit of immunosuppression with FTY720 post MI to prevent progressive pathological remodeling of the heart, which leads to CHF.

MANIFESTATIONS OF HEART INSUFFICIENCY IN MEN UNDER 60 YEARS OLD WITH MYOCARDIAL INFARCTION COMPLICATED WITH ACUTE KIDNEY DAMAGE

2021 ◽  
pp. 120-127
Author(s):  
Golikov A.V. ◽  
Reiza V.A. ◽  
Tassybayev B.B. ◽  
Gordienko A.V.
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Acute Kidney Injury ◽  
Chronic Heart Failure ◽  
Absolute Risk ◽  
Kidney Injury ◽  
Left Ventricular ◽  
Winter Period ◽  
Study Group ◽  
Type I

Relevance. Acute kidney injury in myocardial infarction worsens its prognosis, including due to the development of chronic heart failure. Moreover, most of the data was obtained for patients over 60 years old. Aim. To evaluate the features of the heart failure manifestations in men under 60 years old with myocardial infarction complicated by acute kidney injury to improve prevention and outcomes. Material and methods. The study included men 19-60 years old with type I myocardial infarction. The patients were divided into two age-comparable groups: I - study group, with acute kidney injury - 25 patients; II - control, without it - 486 patients. A comparative analysis of the heart failure main manifestations frequency in the first 48 hours (1) and at the end of the third week of the disease (2), their dynamics, analysis of their impact on the risk of chronic heart failure development in acute kidney injury (ANOVA) was performed. Results. The study group (4.0%) differed from the control (21.8%) in a lower frequency of acrocyanosis (p = 0.03) and liver enlargement (8.0 and 25.7%; respectively; p = 0.046) at the end of the eighth week diseases. The main risk markers of the chronic heart failure development in study group were: winter period of the year (absolute risk: 94.1%; relative - 3.76; p = 0.0003), respiratory infections 2-3 times a year (absolute risk: 81.8%; p = 0.003), left ventricular myocardial mass index1 ≥ 173.3 g/m2 (absolute risk: 100%; p = 0.008) and mean arterial pressure1 ≥ 120 mm Hg (absolute risk: 100%; relative - 1.88; p = 0.01). Conclusions. Men under 60 years old with acute kidney injury in myocardial infarction are characterized by a higher incidence of chronic heart failure. The listed above values of the different predictors should be used in the formation of the high-risk groups for the chronic heart failure in acute kidney injury development, as well as for prognostic modeling.

A translational model of chronic heart failure in rats

2018 ◽  
pp. 136-148
Author(s):  
С.А. Крыжановский ◽  
И.Б. Цорин ◽  
Е.О. Ионова ◽  
В.Н. Столярук ◽  
М.Б. Вититнова ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Chronic Heart Failure ◽  
Left Ventricular ◽  
Compensatory Hypertrophy ◽  
Experimental Myocardial Infarction ◽  
Left Ventricular Ejection ◽  
Translational Model ◽  
Innovative Drug ◽  
Ventricular Ejection Fraction

Цель исследования - разработка трансляционной модели хронической сердечной недостаточности (ХСН) у крыс, позволяющей, с одной стороны, изучить тонкие механизмы, лежащие в основе данной патологии, а с другой стороны, выявить новые биомишени для поиска и изучения механизма действия инновационных лекарственных средств. Методика. Использован комплекс эхокардиографических, морфологических, биохимических и молекулярно-биологических исследований, позволяющий оценивать и дифференцировать этапы формирования ХСН. Результаты. Динамические эхокардиографические исследования показали, что ХСН формируется через 90 дней после воспроизведения переднего трансмурального инфаркта миокарда. К этому времени у животных основной группы отмечается статистически значимое по сравнению со 2-ми сут. после воспроизведения экспериментального инфаркта миокарда снижение ФВ левого желудочка сердца (соответственно 55,9 ± 1,4 и 63,9 ± 1,6%, р = 0,0008). Снижение насосной функции сердца (на 13% по сравнению со 2-ми сут. после операции и на ~40% по сравнению с интактными животными) сопровождается увеличением КСР и КДР (соответственно с 2,49 ± 0,08 до 3,91 ± 0,17 мм, р = 0,0002, и с 3,56 ± 0,11 до 5,20 ± 0,19 мм, р = 0,0001), то есть к этому сроку развивается сердечная недостаточность. Результаты эхокардиографических исследований подтверждены данными морфометрии миокарда, продемонстрировавшими дилатацию правого и левого желудочков сердца. Параллельно проведенные гистологические исследования свидетельствуют о наличии патогномоничных для данной патологии изменений миокарда (постинфарктный кардиосклероз, компенсаторная гипертрофия кардиомиоцитов, очаги исчезновения поперечной исчерченности мышечных волокон и т.д.) и признаков венозного застоя в легких и печени. Биохимические исследования выявили значимое увеличение концентрации в плазме крови биохимического маркера ХСН - мозгового натрийуретического пептида. Данные молекулярно-биологических исследований позволяют говорить о наличии гиперактивности ренин-ангиотензин-альдостероновой и симпатоадреналовой систем, играющих ключевую роль в патогенезе ХСН. Заключение. Разработана трансляционная модель ХСН у крыс, воспроизводящая основные клинико-диагностические критерии этого заболевания. Показано наличие корреляции между морфометрическими, гистологическими, биохимическими и молекулярными маркерами прогрессирующей ХСН и эхокардиографическими диагностическими признаками, что позволяет использовать неинвазивный метод эхокардиографии, характеризующий состояние внутрисердечной гемодинамики, в качестве основного критерия оценки наличия/отсутствия данной патологии. Aim. Development of a translational model for chronic heart failure (CHF) in rats to identify new biotargets for finding and studying mechanisms of innovative drug effect in this disease. Methods. A set of echocardiographic, morphological, biochemical, and molecular methods was used to evaluate and differentiate stages of CHF development. Results. Dynamic echocardiographic studies showed that CHF developed in 90 days after anterior transmural myocardial infarction. By that time, left ventricular ejection fraction was significantly decreased in animals of the main group compared with rats studied on day 2 after experimental myocardial infarction (55.9 ± 1.4% vs . 63.9 ± 1.6%, respectively, p<0.0008). The decrease in heart’s pumping function (by 13% compared with day 2 after infarction and by approximately 40% compared to intact animals) was associated with increased ESD and EDD (from 2.49 ± 0.08 to 3.91 ± 0.17 mm, p = 0.0002, and from 3.56 ± 0.11 to 5.20 ± 0.19 mm, respectively, p = 0.0001); therefore, heart failure developed by that time. The results of echocardiographic studies were confirmed by myocardial morphometry, which demonstrated dilatation of both right and left ventricles. Paralleled histological studies indicated presence of the changes pathognomonic for this myocardial pathology (postinfarction cardiosclerosis, compensatory hypertrophy of cardiomyocytes, foci of disappeared transverse striation of muscle fibers, etc.) and signs of venous congestion in lungs and liver. Biochemical studies demonstrated a significant increase in plasma concentration of brain natriuretic peptide, a biochemical marker of CHF. Results of molecular studies suggested hyperactivity of the renin-angiotensin-aldosterone and sympathoadrenal systems, which play a key role in the pathogenesis of CHF. Conclusions. A translational model of CHF in rats was developed, which reproduced major clinical and diagnostic criteria for this disease. Morphometric, histological, biochemical, and molecular markers for progressive CHF were correlated with echocardiographic diagnostic signs, which allows using this echocardiographic, noninvasive method characterizing the intracardiac hemodynamics as a major criterion for the presence / absence of this pathology.

scholarly journals Uric Acid, Oxidative Stress and Inflammation in Chronic Heart Failure with Reduced Ejection Fraction

2015 ◽  
Vol 23 (4) ◽  
pp. 397-406 ◽  
Author(s):  
Adriana Iliesiu ◽  
Alexandru Campeanu ◽  
Daciana Marta ◽  
Irina Parvu ◽  
Gabriela Gheorghe
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Uric Acid ◽  
Chronic Heart Failure ◽  
Ejection Fraction ◽  
Xanthine Oxidase ◽  
Left Ventricular ◽  
Paraoxonase 1 ◽  
Lv Function ◽  
The Relationship

Abstract Background. Oxidative stress (OS) and inflammation are major mechanisms involved in the progression of chronic heart failure (CHF). Serum uric acid (sUA) is related to CHF severity and could represent a marker of xanthine-oxidase activation. The relationship between sUA, oxidative stress (OS) and inflammation markers was assessed in patients with moderate-severe CHF and reduced left ventricular (LV) ejection fraction (EF). Methods. In 57 patients with stable CHF, functional NYHA class III, with EF<40%, the LV function was assessed by N-terminal of the prohormone brain natriuretic peptide (NT-proBNP) levels and echocardiographically through the EF and E/e’ ratio, a marker of LV filling pressures. The relationship between LV function, sUA, malondialdehyde (MDA), myeloperoxidase (MPO), paraoxonase 1 (PON-1) as OS markers and high sensitivity C-reactive protein (hsCRP) and interleukin 6 (IL-6) as markers of systemic inflammation was evaluated. Results. The mean sUA level was 7.9 ± 2.2 mg/dl, and 61% of the CHF patients had hyperuricemia. CHF patients with elevated LV filling pressures (E/e’ ≥ 13) had higher sUA (8.6 ± 2.3 vs. 7.3 ± 1.4, p=0.08) and NT-proBNP levels (643±430 vs. 2531±709, p=0.003) and lower EF (29.8 ± 3.9 % vs. 36.3 ± 4.4 %, p=0.001). There was a significant correlation between sUA and IL-6 (r = 0.56, p<0.001), MDA (r= 0.49, p= 0.001), MPO (r=0.34, p=0.001) and PON-1 levels (r= −0.39, p= 0.003). Conclusion. In CHF, hyperuricemia is associated with disease severity. High sUA levels in CHF with normal renal function may reflect increased xanthine-oxidase activity linked with chronic inflammatory response.

Abstract 3791: Improved Ventricular-Arterial Coupling After 4 Weeks of Exercise Training in Patients with Chronic Heart Failure

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Marcus Sandri ◽  
Stephan Gielen ◽  
Norman Mangner ◽  
Volker Adams ◽  
Sandra Erbs ◽  
...  
Keyword(s):  
Heart Failure ◽  
Chronic Heart Failure ◽  
Exercise Training ◽  
Endothelial Function ◽  
Training Group ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Control Group ◽  
Lv Function ◽  
Ventricular Ejection Fraction

Background: The concept of ventricular-arterial coupling implies that LV-function is determined by the three factors left ventricular diastolic, left ventricular systolic and arterial elastance. We have previously documented an improvement in endothelial function and systolic LV-function in patients with chronic heart failure (CHF) after 6 months of exercise training (ET). It remains, however, unclear, how shorter ET periods may affect endothelial, systolic and diastolic ventricular function as echocardiographic parameters related to ventricular arterial coupling in patients with CHF. METHODS: In this ongoing study we randomised 43 patients with stable CHF (age 60.3 ± 2.9 years, EF 27.4 ± 1.7%, VO 2 max 14.7 ± 4.3ml/kg*min) to a training or a control group (C). Patients in the training group exercised 4 times daily at 70% of the individual heart rate reserve for 4 weeks under supervision. At baseline and after 4 weeks the E/A ratio and septal/lateral E’/A’ velocities were determined by echocardiography with tissue Doppler. Exercise capacity was measured by ergospirometry and flow-mediated dilatation (FMD) was assessed by high-resolution radial ultrasound. RESULTS: After only 4 weeks of ET oxygen uptake at peak exercise increased from 14.9 ± 3.3 to 18.1 ± 4.7 ml/min/kg, (p<0.01 vs. C) in training subjects. Left ventricular ejection fraction improved from 26.8 ± 4.6 to 33.1 ± 5.5% (p<0.05 vs. C) in patients of the training group while it remained unchanged in the control group. E/A-ratio mended from 0.63 ± 0.12 to 0.81 ± 0.22 (p<0.01 vs. C) in training patients. Septal E’ velocities increased from 5.5 ± 0.5 to 7.8 ± 1.4 cm/s in training patients (p<0.05 vs. C). FMD of the radial artery improved from 8.2 ± 2.1 to 15.2 ± 3.8% (p<0.01 vs. C) as a result of ET. CONCLUSIONS: Only 4 weeks of endurance training are highly effective with significantly improved FMD accompanied by an emended systolic and diastolic LV-function. We hypothesise that the improvement in LV-EF in training patients may be caused by a corrected ventricular-arterial coupling: ventricular diastolic relaxation and effective endothelial function are ameliorated resulting in an augmentation of stroke volume.

Abstract 14664: Reduced Activin Like Kinase 1 Activity Promotes Cardiac Fibrosis in Heart Failure

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Kevin Morine ◽  
Vikram Paruchuri ◽  
Xiaoying Qiao ◽  
Emily Mackey ◽  
Mark Aronovitz ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Remodeling ◽  
Cardiac Fibrosis ◽  
Type I Collagen ◽  
Transforming Growth Factor ◽  
Left Ventricular ◽  
Lv Function ◽  
Type I ◽  
Mrna Levels ◽  
Protein Levels

Introduction: Activin receptor like kinase 1 (ALK1) mediates signaling via transforming growth factor beta-1 (TGFb1), a pro-fibrogenic cytokine. No studies have defined a role for ALK1 in heart failure. We tested the hypothesis that reduced ALK1 expression promotes maladaptive cardiac remodeling in heart failure. Methods and Results: ALK1 mRNA expression was quantified by RT-PCR in left ventricular (LV) tissue from patients with end-stage heart failure and compared to control LV tissue obtained from the National Disease Research Interchange (n=8/group). Compared to controls, LV ALK1 mRNA levels were reduced by 85% in patients with heart failure. Next, using an siRNA approach, we tested whether reduced ALK1 levels promote TGFb1-mediated collagen production in human cardiac fibroblasts. Treatment with an ALK1 siRNA reduced ALK1 mRNA levels by 75%. Compared to control, TGFb1-mediated Type I collagen and pSmad-3 protein levels were 2.5-fold and 1.7-fold higher, respectively, after ALK1 depletion. To explore a role for ALK1 in heart failure, ALK1 haploinsufficient (ALK1) and wild-type mice (WT; n=8/group) were studied 2 weeks after thoracic aortic constriction (TAC). Compared to WT, baseline LV ALK1 mRNA levels were 50% lower in ALK1 mice. Both LV and lung weights were higher in ALK1 mice after TAC. Cardiomyocyte area and LV mRNA levels of BNP, RCAN, and b-MHC were increased similarly, while SERCa levels were reduced in both ALK1 and WT mice after TAC. Compared to WT, LV fibrosis (Figure) and Type 1 Collagen mRNA and protein levels were higher among ALK1 mice. Compared to WT, LV fractional shortening (48±12 vs 26±10%, p=0.01) and survival (Figure) were lower in ALK1 mice after TAC. Conclusions: Reduced LV expression of ALK1 is associated with advanced heart failure in humans and promotes early mortality, impaired LV function, and cardiac fibrosis in a murine model of heart failure. Further studies examining the role of ALK1 and ALK1 inhibitors on cardiac remodeling are required.

Changes in skeletal muscle biochemistry and histology relative to fiber type in rats with heart failure

1997 ◽  
Vol 83 (4) ◽  
pp. 1291-1299 ◽  
Author(s):  
Michael D. Delp ◽  
Changping Duan ◽  
John P. Mattson ◽  
Timothy I. Musch
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Skeletal Muscle ◽  
Enzyme Activities ◽  
Fiber Type ◽  
Left Ventricular ◽  
Type I ◽  
Fiber Composition ◽  
Muscle Biochemistry ◽  
Type I Fibers

Delp, Michael D., Changping Duan, John P. Mattson, and Timothy I. Musch. Changes in skeletal muscle biochemistry and histology relative to fiber type in rats with heart failure. J. Appl. Physiol. 83(4): 1291–1299, 1997.—One of the primary consequences of left ventricular dysfunction (LVD) after myocardial infarction is a decrement in exercise capacity. Several factors have been hypothesized to account for this decrement, including alterations in skeletal muscle metabolism and aerobic capacity. The purpose of this study was to determine whether LVD-induced alterations in skeletal muscle enzyme activities, fiber composition, and fiber size are 1) generalized in muscles or specific to muscles composed primarily of a given fiber type and 2) related to the severity of the LVD. Female Wistar rats were divided into three groups: sham-operated controls ( n = 13) and rats with moderate ( n = 10) and severe ( n = 7) LVD. LVD was surgically induced by ligating the left main coronary artery and resulted in elevations ( P < 0.05) in left ventricular end-diastolic pressure (sham, 5 ± 1 mmHg; moderate LVD, 11 ± 1 mmHg; severe LVD, 25 ± 1 mmHg). Moderate LVD decreased the activities of phosphofructokinase (PFK) and citrate synthase in one muscle composed of type IIB fibers but did not modify fiber composition or size of any muscle studied. However, severe LVD diminished the activity of enzymes involved in terminal and β-oxidation in muscles composed primarily of type I fibers, type IIA fibers, and type IIB fibers. In addition, severe LVD induced a reduction in the activity of PFK in type IIB muscle, a 10% reduction in the percentage of type IID/X fibers, and a corresponding increase in the portion of type IIB fibers. Atrophy of type I fibers, type IIA fibers, and/or type IIB fibers occurred in soleus and plantaris muscles of rats with severe LVD. These data indicate that rats with severe LVD after myocardial infarction exhibit 1) decrements in mitochondrial enzyme activities independent of muscle fiber composition, 2) a reduction in PFK activity in type IIB muscle, 3) transformation of type IID/X to type IIB fibers, and 4) atrophy of type I, IIA, and IIB fibers.

Abstract 3295: De-induction of the Maladaptive Fetal Gene Program During Chronic Monotherapy with Metoprolol Succinate is Retained Following Withdrawal of Therapy in Dogs with Chronic Heart Failure

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Rasha Bazari ◽  
Sharad Rastogi ◽  
Valerio Zaca ◽  
Sidney Goldstein ◽  
Hani N Sabbah
Keyword(s):  
Heart Failure ◽  
Chronic Heart Failure ◽  
Mrna Expression ◽  
Natriuretic Peptide ◽  
Left Ventricular ◽  
Lv Function ◽  
Metoprolol Succinate ◽  
Myosin Heavy Chain Isoform ◽  
Chronic Therapy ◽  
Lv Remodeling

Background: Chronic therapy with extended release metoprolol succinate (MET), a selective β1 adrenergic receptor blocker, improves left ventricular (LV) function and attenuates global LV remodeling in dogs with chronic heart failure (HF). We previously showed that chronic therapy with β-blockade results in de-induction of the fetal gene program (FGP) in LV myocardium of dogs with HF. In this study, we tested the hypothesis that in dogs with HF withdrawal of chronic MET does not lead to re-induction of FGP. Methods: Studies were performed in 17 intracoronary microembolization-induced HF dogs randomized to 3 months oral therapy with MET (100 mg, once daily, n=11) or no therapy at all (Controls, n=6). In dogs randomized to MET, 6 were sacrificed after 3 months of therapy and in the remaining 5, MET was withdrawn after 3 months of therapy and dogs were observed for 6 weeks after withdrawal of MET (MET-W) and then sacrificed. LV tissue was also obtained from 6 normal (NL) dogs for comparison. mRNA expression of the FGP genes namely, atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), sarcoplasmic reticulum calcium ATPase (CAA), cardiac β-1 adren-ergic receptor (AR) and α-myosin heavy chain isoform (α-MHC) was measured using reverse transcriptase polymerase chain reaction (RT-PCR) and bands were quantified in densitometric units (du). Results: In Controls, mRNA expression of ANP and BNP increased and expression of CAA, β 1-AR and α-MHC decreased. Treatment with MET decreased expression of ANP and BNP and increased expression of CAA, β 1-AR and α-MHC. Except for α-MHC, the improvement in FGP seen during MET treatment was preserved in MET-W dogs. Conclusions: Withdrawal of MET is associated with sustained de-induction of the FGP in LV myocardium of dogs with HF. This observation supports the concept that chronic β-blockade therapy in HF confers lasting reversal of LV remodeling and molecular recovery of the failing myocardium.

Plasma cardiotrophin-1 following acute myocardial infarction: relationship with left ventricular systolic dysfunction

2001 ◽  
Vol 102 (1) ◽  
pp. 9-14 ◽  
Author(s):  
Suneel TALWAR ◽  
Iain B. SQUIRE ◽  
Russell J. O'BRIEN ◽  
Paul F. DOWNIE ◽  
Joan E. DAVIES ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Acute Myocardial Infarction ◽  
Left Ventricular Systolic Dysfunction ◽  
Systolic Function ◽  
Systolic Dysfunction ◽  
Clinic Visit ◽  
Left Ventricular ◽  
Lv Function ◽  
Ventricular Remodelling

The glycoprotein 130 (gp130) signalling pathway is important in the development of heart failure. Cardiotrophin-1 (CT-1), a cytokine acting via the gp130 pathway, is involved in the process of ventricular remodelling following acute myocardial infarction (AMI) in animals. The aims of the present study were to examine the profile of plasma CT-1 following AMI in humans, and its relationship with echocardiographic parameters of left ventricular (LV) systolic function. Serial measurements of plasma CT-1 levels were made in 60 patients at 14-48h, 49-72h, 73-120h and 121-192h following AMI and at a later clinic visit. LV function was assessed using a LV wall motion index (WMI) score on admission (WMI-1) and at the clinic visit (WMI-2). Compared with values in control subjects (29.5±3.6fmol/ml), the plasma CT-1 concentration was elevated in AMI patients at 14-48h (108.1±15.1fmol/ml), 49-72h (105.2±19.7fmol/ml), 73-120h (91.2±14.9fmol/ml) and 121-192h (118.8±22.6fmol/ml), and at the clinic visit (174.9±30.9 fmol/ml) (P < 0.0001). Levels were higher following anterior compared with inferior AMI. For patients with anterior AMI, CT-1 levels were higher at the clinic visit than at earlier times. WMI-1 correlated with CT-1 at all times prior to hospital discharge (P < 0.05). On best subsets analysis, the strongest correlate with WMI-1 was CT-1 level at 49-72h (R2 = 20%, P < 0.05). In conclusion, plasma levels of CT-1 are elevated soon after AMI in humans and rise further in the subsequent weeks in patients after anterior infarction. CT-1 measured soon after AMI is indicative of LV dysfunction, and this cytokine may have a role in the development of ventricular remodelling and heart failure after AMI.

scholarly journals Heart functional and structural compendium of cardiosplenic and cardiorenal networks in acute and chronic heart failure pathology

2018 ◽  
Vol 314 (2) ◽  
pp. H255-H267 ◽  
Author(s):  
Ganesh V. Halade ◽  
Vasundhara Kain ◽  
Kevin. A. Ingle
Keyword(s):  
Heart Failure ◽  
Chronic Heart Failure ◽  
Temporal Dynamics ◽  
Inflammatory Responses ◽  
Function Analysis ◽  
Left Ventricular ◽  
Integrative Approach ◽  
Lv Function ◽  
Renal Histology ◽  
Pathological Remodeling

Heart failure (HF) secondary to myocardial infarction (MI) is linked to kidney complications that comprise cellular, structural, functional, and survival indicators. However, HF research is focused on left ventricular (LV) pathology. Here, we determined comprehensive functional analysis of the LV using echocardiography in transition from acute heart failure (AHF) to progressive chronic heart failure (CHF) pathology and developed a histological compendium of the cardiosplenic and cardiorenal networks in pathological remodeling. In surgically induced MI using permanent coronary ligation, the LV dysfunction is pronounced, with myocardium necrosis, wall thinning, and 20–30% LV rupture events that indicated AHF and CHF pathological remodeling in C57BL/6 male mice (2–4 mo old, n = 50). Temporal LV function analysis indicated that fractional shortening and strain are reduced from day 1 to day 5 in AHF and sustained to advance to CHF from day 28 to day 56 compared with naïve control mice ( n = 6). During the transition of AHF ( day 1 to day 5) to advanced CHF ( day 28 to day 56), histological and cellular changes in the spleen were definite, with bimodal inflammatory responses in kidney inflammatory biomarkers. Likewise, there was a unidirectional, progressive, and irreversible deposition of compact collagen in the LV along with dynamic changes in the cardiosplenic and cardiorenal networks post-MI. The renal histology and injury markers suggested that cardiac injury triggers irreversible dysregulation that actively alters the cardiosplenic and cardiorenal networks. In summary, the novel strategies or pathways that modulate comprehensive cardiosplenic and cardiorenal networks in AHF and CHF would be effective approaches to study either cardiac repair or cardiac pathology. NEW & NOTEWORTHY The present compendium shows irreversible ventricular dysfunction as assessed by temporal echocardiography while histological and structural measurements of the spleen and kidney added a novel direction to study cardiosplenic and cardiorenal networks in heart failure pathology. Therefore, the consideration of systems biology and integrative approach is essential to develop novel treatments. Listen to this article's corresponding podcast at http://ajpheart.podbean.com/e/temporal-dynamics-of-acute-and-chronic-heart-failure/ .

scholarly journals Corticotropin releasing hormone receptor 2 exacerbates chronic cardiac dysfunction

2017 ◽  
Vol 214 (7) ◽  
pp. 1877-1888 ◽  
Author(s):  
Takuma Tsuda ◽  
Mikito Takefuji ◽  
Nina Wettschureck ◽  
Kazuhiko Kotani ◽  
Ryota Morimoto ◽  
...  
Keyword(s):  
Heart Failure ◽  
Chronic Heart Failure ◽  
Cardiac Dysfunction ◽  
Hormone Receptor ◽  
Adenosine Monophosphate ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Corticotropin Releasing Hormone ◽  
Ventricular Ejection Fraction ◽  
Releasing Hormone

Heart failure occurs when the heart is unable to effectively pump blood and maintain tissue perfusion. Despite numerous therapeutic advancements over previous decades, the prognosis of patients with chronic heart failure remains poor, emphasizing the need to identify additional pathophysiological factors. Here, we show that corticotropin releasing hormone receptor 2 (Crhr2) is a G protein–coupled receptor highly expressed in cardiomyocytes and continuous infusion of the Crhr2 agonist, urocortin 2 (Ucn2), reduced left ventricular ejection fraction in mice. Moreover, plasma Ucn2 levels were 7.5-fold higher in patients with heart failure compared to those in healthy controls. Additionally, cardiomyocyte-specific deletion of Crhr2 protected mice from pressure overload-induced cardiac dysfunction. Mice treated with a Crhr2 antagonist lost maladaptive 3′-5′-cyclic adenosine monophosphate (cAMP)–dependent signaling and did not develop heart failure in response to overload. Collectively, our results indicate that constitutive Crhr2 activation causes cardiac dysfunction and suggests that Crhr2 blockade is a promising therapeutic strategy for patients with chronic heart failure.

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