scholarly journals Parameters of left atrial during stress in patients with asymptomatic primary mitral regurgitation

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
R Zvirblyte ◽  
E Tamulenaite ◽  
A Saniukaite ◽  
I Merkyte ◽  
V Mizariene ◽  
...  
Keyword(s):  
Left Ventricle ◽  
Mitral Regurgitation ◽  
Structural Changes ◽  
Peak Stress ◽  
Myocardial Deformation ◽  
Volume Index ◽  
Control Group ◽  
Deformation Parameters ◽  
Asymptomatic Patients ◽  
Primary Mitral Regurgitation

Abstract Introduction Progressive volume overload caused by chronic mitral regurgitation (MR) leads to left atrium (LA) and left ventricle (LV) remodeling. Despite these structural changes, most of MR patients may remain asymptomatic for a long time. LA enlargement and reduced LA deformation parameters in asymptomatic MR patients predict a worse prognosis and may provide additional information to guide for earlier surgery. Purpose The aim of the study was to evaluate changes of LA size and deformation parameters in patients with asymptomatic primary MR during stress. Methods 84 asymptomatic patients (age 59.87±13.47 years) with sinus rhythm and preserved left ventricle (LV) ejection fraction (EF) (>50%) at rest were included in the study. Resting and stress (veloergometry as per protocol 25 + 25 W every 3 minutes) echocardiography and speckle tracking off-line analyses were performed to 52 (61.9%) patients with moderate MR (MR group) and 32 (38.1%) patients without significant heart valves disease (control group). Statistical analyses were performed using the SPSS 20.0 software. The value of p<0.05 was considered as statistically significant. Results Volume index of LA was significantly higher in subjects with MR (picture 1). LA area was similar in MR and control groups at rest. However, during stress LA area became significantly larger in MR group (picture 1). LA myocardial deformation parameters were calculated during 3 phases of LA cycle: reservoir phase strain (LASr), conduit phase strain (LAScd), contraction phase strain (LASct). At rest, during peak stress and at recovery phase all of them were higher in controls but difference was not significant. During initial stress (25 W) LAScd was significantly higher in MR group (−16.86±−8.06% vs. −11.33 ±−6.26% p=0.034), while healthy subjects had a tendency to lower LASr (20.32±10.53% vs. 22.7±10.89%, p=0.535) (picture 1). Better LV EF at rest was related to smaller LA area (p=0.003, r – 0.390) and volume index (p=0.020, r – 0.308) during peak stress. Conclusions Stress provokes significant increase of LA size (volume and area) and LAScd in patients with primary mitral regurgitation. Other myocardial deformation parameters of LA were not significantly related to MR. LV EF at rest correlates with LA parameters during peak stress. Changes of LA parameters during stress Funding Acknowledgement Type of funding source: None

481Right ventricular longitudinal strain predicts symptoms in patients with chronic primary mitral regurgitation

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
A L Chilingaryan ◽  
L G Tunyan ◽  
K G Adamyan
Keyword(s):  
Mitral Regurgitation ◽  
Ejection Fraction ◽  
Left Atrial ◽  
Longitudinal Strain ◽  
Global Longitudinal Strain ◽  
Volume Index ◽  
Asymptomatic Patients ◽  
Lv Ejection Fraction ◽  
Primary Mitral Regurgitation

Abstract Mitral regurgitation (MR) leads to subclinical changes that often cannot be detected by low sensitive conventional parameters and early predictors of deterioration could suggest a better timing for intervention. Methods We follow up 175 asymptomatic patients 56±13 years (79 female) with severe primary MR in sinus rhythm and without diabetes mellitus and renal disease for 2 years. Global longitudinal strain (LS) of left ventricle (LVGLS), right ventricular (RV) free wall LS (RVLS), and left atrial (LA) peak reservoir LS as average of two basal segments in 4 chamber view were measured by speckle tracking along with indexes of LV end-systolic and end-diastolic volumes, LV ejection fraction (EF), left atrial end-systolic volume index (LAVi) every 6 months. Normal reference values of LS were obtained from age and sex matched 40 healthy controls. Results Patients with MR had higher LV ejection fraction (EF), LVGLS, LALS and lower values of RVLS compared with controls (EF 67.4±5% vs 59.3±4%, p<0.05; LVGLS –25.2±2.3% vs –21.2±1.9%, p<0.03; LALS 46.2±5.1% vs 42.4±3.7%, p<0.04; RVLS –23.4±5.1% vs –27.3±2.8%, p<0.03). 53 (30%) patients developed symptoms at exercise during follow up. Symptomatic patients at baseline had higher values of RVLS compared with patients who remained asymptomatic during follow up without significant differences in EF, LVGLS, LALS (RVLS –21.4±2.6% vs –25.8±3.2%, p<0.02; EF 66.8±2.4% vs 68.1±3.1%, p>0.05; LVGLS –24.8±2.1% vs –25.3±2.3%, p>0.05; LALS 45.7±4.1% vs 46.5±4.4%, p>0.05). RVLS correlated with LAVi (r=0.53, p<0.01) and LALS (r=0.57, p<0.01). Regression analysis defined RVLS as an independent predictor of symptoms development (OR=3.2; 95% CI=1.37–7.63; p<0.01). Conclusion RV longitudinal strain predicts symptoms in patients with chronic primary mitral regurgitation.

scholarly journals P293 Assessment of right ventricle parameters during stress in patients with asymptomatic primary mitral regurgitation

2020 ◽  
Vol 21 (Supplement_1) ◽  
Author(s):  
R Zvirblyte ◽  
E Tamulenaite ◽  
I Merkyte ◽  
A Saniukaite ◽  
J J Vaskelyte
Keyword(s):  
Mitral Regurgitation ◽  
Right Ventricle ◽  
Global Longitudinal Strain ◽  
Recovery Phase ◽  
Control Group ◽  
Contractile Reserve ◽  
Surgical Interventions ◽  
Asymptomatic Patients ◽  
Primary Mitral Regurgitation ◽  
Rv Function

Abstract Background Evaluation of right ventricle (RV) function and pulmonary artery pressure (PAP) during stress, plays an important role in identifying worse prognosis for patients with chronic mitral regurgitation (MR) and may help to optimise the time of surgical interventions. Purpose The aim of the study was to evaluate changes of RV function and systolic PAP in patients with asymptomatic primary MR during stress echocardiography. Methods Resting and stress (veloergometry as per protocol 25 + 25 W every 3 minutes) echocardiography were performed in 63 asymptomatic patients (age 56.12 ± 13.97 years) with preserved left ventricle (LV) ejection fraction (EF) (&gt;50%) at rest. 39 (61.9%) patients with moderate (grade 2-3) MR (MR group) and 24 (38.1%) patients without significant heart valves disease (control group) were included in the study. Statistical analyses were performed using the SPSS 20.0 software. The value of p &lt; 0.05 was considered as statistically significant. Results Anthropometric and clinical characteristics, LV EF (64.96 ± 9.14% vs. 64.87 ± 6.46%, p = 0.97) and LV global longitudinal strain (GLS) (-19.24± 3.12% vs. -19.28 ± 3.36%, p = 0.055) at rest were not significantly different between MR and control groups. Diameter of RV was larger in MR group (36.07 ± 5.34 mm vs. 33.13 ± 3.48 mm) however difference was not significant (p = 0.971). Parameters of RV function (longitudinal myocardial velocity - S’, fractional area change (FAC) and tricuspid annular plane systolic excursion (TAPSE)) were similar in both groups at rest, during stress and at recovery phase (Picture 1). However TAPSE and S’ at rest (p = 0.037 and p = 0.205, respectively) and minimal stress (p = 0.006 and p = 0.035, respectively) were significantly lower in patients with MR who had highly increased (&gt;60 mmHg) systolic PAP during stress. Also TAPSE (p = 0.002) and S’ (p = 0.017) during recovery phase were significantly lower in subjects with reduced LV contractile reserve (whom LV EF increased &lt;4% or GLS &lt;1.9% during stress). Systolic PAP during stress was growing much faster in patients with MR (Picture 1). Conclusions Patients with asymptomatic moderate primary mitral regurgitation had higher systolic PAP during stress even though at rest it was similar as in controls. Prominent severe pulmonary hypertension during stress was related to worsening parameters of RV function. Abstract P293 Figure. Parameters of RV during stress

Reference values for two-dimensional myocardial strain echocardiography of the left ventricle in healthy children

2019 ◽  
Vol 29 (3) ◽  
pp. 325-337
Author(s):  
Laurens P. Koopman ◽  
Bas Rebel ◽  
Devi Gnanam ◽  
Mirthe E. Menting ◽  
Willem A. Helbing ◽  
...  
Keyword(s):  
Left Ventricle ◽  
Strain Rate ◽  
Longitudinal Strain ◽  
Circumferential Strain ◽  
Left Ventricular ◽  
Myocardial Deformation ◽  
Healthy Children ◽  
Deformation Parameters ◽  
Strain And Strain Rate ◽  
Echocardiographic Parameters

AbstractBackgroundMyocardial deformation by speckle tracking echocardiography provides additional information on left ventricular function. Values of myocardial deformation (strain and strain rate) depend on the type of ultrasound machine and software that is used. Normative values for QLAB (Philips) are scarce, especially for children. It is important to evaluate the influence of age and body size on myocardial deformation parameters, since anthropometrics strongly influence many standard echocardiographic parameters. The aim of this study was to provide comprehensive normal values for myocardial deformation of the left ventricle using a Philips platform and to evaluate the association with anthropometric and standard echocardiographic parameters.MethodsHealthy children between 1 and 18 years of age were prospectively examined using a standard echocardiographic protocol. Short-axis and apical four-chamber, two-chamber, and three-chamber views were used to measure peak systolic circumferential and longitudinal strain and systolic and early diastolic strain rate of the left ventricle using dedicated software.ResultsA total of 103 children were included with a mean age of 10.8 and inter-quartile range 7.3–14.3 years. Global circumferential strain values (±SD) were −24.2±3.5% at basal, −25.8±3.5% at papillary muscle, and −31.9±6.2% at apex levels. Global left ventricular longitudinal strain values were −20.6±2.6% in apical four-chamber view, −20.9±2.7% in apical two-chamber, and −21.0 ±2.7% in apical three-chamber. Age was associated with longitudinal strain, longitudinal systolic and early diastolic strain rate, but not with circumferential strain.ConclusionsNormal values for left ventricular deformation parameters in children are obtained using a Philips platform. Age partly explains normal variation of strain and strain rate.

Donation after circulatory death hearts recipients compared to donation after brain death heart recipients have comparable systolic left ventricular function and better myocardial strain at 1 year

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
A Ciarka ◽  
A Page ◽  
S Messer ◽  
E Pavlushkov ◽  
S Tsui ◽  
...  
Keyword(s):  
Left Ventricle ◽  
Left Ventricular ◽  
Myocardial Deformation ◽  
Lv Function ◽  
Donation After Circulatory Death ◽  
Deformation Parameters ◽  
Echocardiographic Parameters ◽  
Donation After Brain Death ◽  
Circulatory Death

Abstract Purpose Cardiac transplantation from donation after circulatory death (DCD) has been implemented at our hospital since February 2015. Despite encouraging results some concerns may be raised about the impact of the warm ischemia and reperfusion injury on the myocardium status at longer follow-up. Therefore, we aimed to analyse systolic performance of the left ventricle at 1 year follow in DCD and donation after brain death (DBD) cardiac recipients, as assessed by echocardiography with myocardial deformation imaging. Methods We identified 46 consecutive DCD cardiac recipients who were transplanted from February 2015 to August 2018 and we matched them with 46 DBD cardiac recipients. Six and 7 patients from DCD and DBD group, respectively, died in the first-year post transplant. In the remaining patients we have compared the classical echocardiographic measurements as well as global longitudinal strain (GLS) and global circumferential strain (GCS) at 1-year follow-up. Results DCD and DBD patients did not present with differences in terms of classical echocardiographic parameters of left ventricular (LV) structure and systolic function at one-year follow-up. LVEDV was similar in DCD and DBD patients (101±24 vs. 95±32 ml, p=0.4 respectively), as well as LVESV (42±13 vs. 42±16 ml, p=0.9, respectively), LV ejection fraction (58±6 vs. 56±8%, p=0.22) and LV mass (156±39 vs. 163±38 gr, p=0.2, respectively). In contrast, myocardial deformation parameters, such as GLS and GCS, were better in DCD than in DBD (16.1 vs. −14.5%, p&lt;0.01; and −25.2 vs. 22.3%, p&lt;0.05, respectively). The diastolic LV function parameters were similar in DCD and DBD group, as evidenced by E wave velocity, A wave velocity and deceleration time of mitral inflow, however E over E prime was lower in DCD than in DBD recipients (7.7±8.7, p&lt;0.05). Fractional area change of the right ventricle was higher in DCD in comparison with DBD (46±7 vs. 40±7%, p&lt;0.01) while right atrial volume index was lower in DCD than in DBD (25±8 vs. 29±9 ml/m2, p&lt;0.01). Other parameters of RV function (systolic excursion of the tricuspid annulus, TAPSE) were similar in both groups. Conclusion DCD and DBD heart recipients present with similar systolic LV function at 1-year follow, as assessed by classical echocardiographic parameters. DCD cardiac recipients have better myocardial deformation parameters as assessed by the speckle tracking, better systolic right ventricular function and lower filling pressures of the left ventricle. Funding Acknowledgement Type of funding source: None

scholarly journals P903 Myocardial work in moderate to severe aortic versus primary mitral regurgitation

2020 ◽  
Vol 21 (Supplement_1) ◽  
Author(s):  
M Bouziane ◽  
R E Dulgheru ◽  
S Marchetta ◽  
S Khaddi ◽  
F Cozza ◽  
...  
Keyword(s):  
Mitral Regurgitation ◽  
Global Longitudinal Strain ◽  
Left Ventricular ◽  
Lv Function ◽  
Severe Aortic Regurgitation ◽  
Asymptomatic Patients ◽  
Work Index ◽  
Valvular Stenosis ◽  
Primary Mitral Regurgitation ◽  
Global Work

Abstract Funding Acknowledgements None OnBehalf None BACKGROUND Myocardial work is an emerging non-invasive technic based on echocardiographic pressure-strain loops that assess left ventricular (LV) function. The method was studied in a large variety of pathologies, but its role in the assessment of valvular regurgitations is still unknown. PURPOSE To compare myocardial work indices in moderate and severe aortic and primary mitral regurgitation. METHODS Seventy-eight patients with moderate and severe aortic regurgitation (AR) or primary mitral regurgitation (MR) and preserved LV ejection fraction (LVEF &gt; 50%) were retrospectively analyzed.. Patients with significant valvular stenosis were excluded. Demographic, clinical and echocardiographic data, including LV global longitudinal strain (GLS) and myocardial work indices, were assessed. RESULTS The mean age was 58 ± 14 years, and 46 patients (59%) were men. Thirty seven patients had moderate or severe AR and 41 patients had moderate or severe MR. The two groups were homogeneous in terms of demographic and clinical data, except for age. As expected, diastolic blood pressure was lower in patients with AR compared to MR group (67 ± 8 mmHg vs. 73 ± 10 mmHg, p = 0,003), patients with MR had a higher LVEF compared to AR group (63 ± 6% vs 59 ± 6%, p = 0,03), and a higher left atrial indexed volume (53 ± 16ml/m² vs 34 ± 12ml/m², p &lt; 0.0001). Overall, GLS, myocardial work index (GWI) and myocardial constructive work (GCW) were significantly lower in patients with moderate or severe AR compared to MR ( -18,1 ±3% vs -21,3 ±3,3%, p &lt; 0,0001; 1849 ± 393 vs 2285 ± 499, p &lt; 0,0001; and 2194 ± 395 vs 2576 ± 594, p = 0,003, respectively). Global wasted work (GWW) and global work efficiency (GWE) were similar. When comparing only asymptomatic patients, results were similar, with higher GLS, GWI and GCW in moderate to severe MR vs. AR (-22,9 ± 3,4 vs.-18,4 ± 3,4%, p &lt;0,001; 2446 ± 570 vs. 1927 ± 338, p = 0.001 and 2767 ± 688 vs. 2236 ± 377, p = 0.005). Interestingly, when comparing asymptomatic patients with a LVEF &gt; 50% for AR, and LVEF &gt; 60% for MR, GWI and GCW were significantly lower in MR group, despite higher GLS values (1852 ± 398 vs. 2322 ± 527, p &lt; 0.001; 2194 ± 400 vs. 2615 ± 638, p = 0.005; -22,1 ± 3,3% vs. -18,2 ± 2,9, p &lt; 0.001). CONCLUSION Patients with moderate to severe MR have higher values of GLS, global work index and global constructive myocardial work. This could translate into the fact that in moderate or severe MR, the myocardium develops a higher amount of work than in AR, maybe to account for the loss of stroke volume into the left atrium. In asymptomatic moderate to severe MR with LVEF &gt; 60%, LV myocardium develops less work than in moderate to severe AR with a LVEF &gt; 50%, suggesting maybe a compensated state.

scholarly journals Left Ventricular Myocardial Function in a Cat with Nonspecific Cardiomyopathy Phenotype

2020 ◽  
Vol 48 ◽  
Author(s):  
Thaís Gomes Barbosa ◽  
Mariana De Resende Coelho ◽  
Ruthnea Aparecida Lázaro Muzzi ◽  
Ana Flávia Silva Pereira ◽  
Luiz Eduardo Duarte de Oliveira ◽  
...  
Keyword(s):  
Left Ventricle ◽  
Left Atrium ◽  
Structural Changes ◽  
Myocardial Dysfunction ◽  
Clinical Signs ◽  
Left Ventricular ◽  
Myocardial Deformation ◽  
Two Dimensional ◽  
Echocardiographic Examination ◽  
Cardiac Evaluation

Background: Non-specific phenotype feline cardiomyopathy (CFNE) is one that does not fit properly in the other categories, and it is necessary to describe in detail the morphology and cardiac function. The causes of CFNE is not very clear, and it may be due to congenital or acquired disease, or also to primary or secondary myocardial dysfunction associated with other conditions. In symptomatic cases, the clinical signs observed are compatible with left congestive heart failure (ICCE). This study reports a CFNE case in an asymptomatic cat, in order to demonstrate the importance of echocardiographic examination in the early diagnosis of the disease.Case: A 6.5-year-old non-neutered crossbred cat weighing 3.1 kg was seen at the institution's veterinary hospital for routine cardiac evaluation. No clinical signs were reported in the history. On physical examination, the animal presented calm behavior, body score 5/9, heart rate 200 bpm, systolic blood pressure of 102 mmHg, respiratory rate 64 mrp, and other normal parameters. CBC and urinalysis laboratory tests were requested, which were unchanged. The electrocardiogram showed normal patterns. In the conventional echocardiographic examination, a significant increase in the left atrium (LA) was observed, and the LA/Ao ratio was 2.05 and the diastolic function was abnormal. There was no presence of concentric hypertrophy of the left ventricle (LV), the thickness of the ventricular wall measured at different points, in the two-dimensional mode and the M mode, was less than 5 millimeters. Other parameters of conventional echocardiography were within the normal range. Through these echocardiographic findings, the suggestive diagnosis was non-specific phenotype cardiomyopathy, with a significant increase in LA. For the assessment of left ventricular myocardial deformation, the strain (St%) and strain rate (StR 1/s) indexes (which correspond to the percentage and speed at which the myocardial fiber deforms during the cardiac cycle, respectively) were evaluated using two-dimensional feature tracking (2D-FTI), with the aid of Xstrain version 10.1 software, optical flow algorithm (ESAOTE®). This analysis showed a decrease in the overall value of the longitudinal and radial St/StR variables.Discussion: The CFNE echocardiographic examination can demonstrate several structural cardiac changes that are not characterized in any other category of cardiomyopathy. Although the patient is still asymptomatic, the echocardiogram made it possible to identify structural changes compatible with the reported disease (enlargement of the left atrium and left ventricular myocardial deformation). Using the 2D-FTI technique, the vulnerability of the myocardial fibers in the longitudinal and radial directions of the left ventricle was observed, demonstrating that despite the patient still not showing clinical signs, there were already signs of ventricular dysfunction. These changes observed by the 2D-FTI technique, suggest that the patient may develop clinical signs of ICCE, resulting from pleural effusion and/or pulmonary edema, requiring more frequent reassessments. For this reason, animals with CFNE should undergo periodic cardiac evaluation to monitor the evolution of the patient's clinical condition. The use of more specific tools, such as 2D-FTI, allows an earlier assessment of clinical changes, which provides a faster therapeutic intervention when necessary, preventing the patient from abruptly decompressing.

scholarly journals Myocardial deformation techniques as potential tools to detect arrhythmogenic cardiomyopathy in early stages of the disease

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
D Segura Rodriguez ◽  
F J Bermudez-Jimenez ◽  
L Gonzalez Camacho ◽  
J M Oyonarte-Ramirez ◽  
E Moreno Escobar ◽  
...  
Keyword(s):  
Global Longitudinal Strain ◽  
Regional Wall Motion ◽  
Pathogenic Mutation ◽  
Left Ventricular ◽  
Myocardial Deformation ◽  
Control Group ◽  
Arrhythmogenic Cardiomyopathy ◽  
Early Stages ◽  
Mechanical Dispersion ◽  
Deformation Parameters

Abstract Introduction Arrhythmogenic Cardiomyopathy (ACM) is a life-threatening entity which predispose to malignant arrhythmias and sudden cardiac death even in early stages of the disease. Deformation techniques obtained by echocardiography are promising tools which can identify subtle pathologic changes in the myocardial wall. Our aim is to investigate how myocardial deformation parameters may be affected throughout ACM spectrum. Methods A cohort of ACM 45 subjects, was characterized using advanced transthoracic echocardiography and divided into groups according to left ventricle ejection fraction (LVEF). Twenty-three healthy volunteers were also included as control group (CG). We analyzed regional wall motion abnormalities and left ventricular myocardial deformation parameters by 2D Speckle Tracking, such as global longitudinal strain (GLS), mechanical dispersion (MD) [standard deviation (SD) and range (delta)]. Results 23 (51,1%) of the ACM cohort were men, with a mean age of 43,13±16,55 years. Next-generation sequencing identified a potential pathogenic mutation in 37 (82,2%) of the patients. Those ACM subjects with low LVEF (ACM-L) presented lower GLS values when compared to those with normal LVEF (ACM-N) (−16,17±2,68% vs. ACM-N −19,39±2,97%; p&lt;0.001) with no significant differences in MD parameters. ACM-N showed no differences in GLS regarding to CG, but significant differences were found when analyzing MD values, with pathological dispersion times in the ACM-N group (ACM-N DMSD 50,50±20,39ms vs. CG 37,35±17,15ms; p=0,016; ACM-N DMDelta 167,4583±75,07ms vs CG 125±49,13ms; p=0,033). Conclusions MD may be an additive tool for identifying ACM patients in early stages of the disease when LVEF is still preserved. FUNDunding Acknowledgement Type of funding sources: None.

scholarly journals Doxorubicin triggers splenic contraction and irreversible dysregulation of COX and LOX that alters the inflammation-resolution program in the myocardium

2018 ◽  
Vol 315 (5) ◽  
pp. H1091-H1100 ◽  
Author(s):  
Jeevan Kumar Jadapalli ◽  
Griffin W. Wright ◽  
Vasundhara Kain ◽  
Mohammad Asif Sherwani ◽  
Ravi Sonkar ◽  
...  
Keyword(s):  
Left Ventricle ◽  
Structural Changes ◽  
Low Dose ◽  
Chronic Phase ◽  
Saline Control ◽  
Control Group ◽  
High Dose ◽  
Saline Control Group ◽  
Inflammation Resolution ◽  
Acute And Chronic Exposure

Doxorubicin (DOX) is a widely used drug for cancer treatment as a chemotherapeutic agent. However, the cellular and integrative mechanism of DOX-induced immunometabolism is unclear. Two-month-old male C57BL/6J mice were divided into high- and low-dose DOX-treated groups with a maintained saline control group. The first group was injected with a high dose of DOX (H-DOX; 15 mg·kg−1·wk−1), and the second group was injected with 7.5 mg·kg−1·wk−1 as a latent low dose of DOX (LL-DOX). H-DOX treatment led to complete mortality in 2 wk and 70% survival in the LL-DOX group compared with the saline control group. Therefore, an additional group of mice was injected with an acute high dose of DOX (AH-DOX) and euthanized at 24 h to compare with LL-DOX and saline control groups. The LL-DOX and AH-DOX groups showed obvious apoptosis and dysfunctional and structural changes in cardiac tissue. Splenic contraction was evident in AH-DOX- and LL-DOX-treated mice, indicating the systems-wide impact of DOX on integrative organs of the spleen, which is essential for cardiac homeostasis and repair. DOX dysregulated splenic-enriched immune-sensitive lipoxygenase and cyclooxygenase in the spleen and left ventricle compared with the saline control group. As a result, lipoxygenase-dependent D- and E-series resolvin precursors, such as 16HDoHE, 4HDoHE, and 12-HEPE, as well as cyclooxygenase-mediated PG species (PGD2, PGE2, and 6-keto-PG2α) were decreased in the left ventricle, suggestive of defective immunometabolism. Both AH-DOX and LL-DOX induced splenic contraction and expansion of red pulp with decreased CD169+ metallophilic macrophages. AH-DOX intoxicated macrophages in the spleen by depleting CD169+ cells in the acute setting and sustained the splenic macrophage loss in the chronic phase in the LL-DOX group. Thus, DOX triggers a vicious cycle of splenocardiac cachexia to facilitate defective immunometabolism and irreversible macrophage toxicity and thereby impaired the inflammation-resolution program. NEW & NOTEWORTHY Doxorubicin (DOX) triggered splenic mass loss and decreased CD169 with germinal center contraction in acute and chronic exposure. Cardiac toxicity of DOX is marked with dysregulation of immunometabolism and thereby impaired resolution of inflammation. DOX suppressed physiological levels of cytokines and chemokines with signs of splenocardiac cachexia.

Sign in / Sign up

Export Citation Format

Share Document