scholarly journals Normal M-mode echocardiographic indices of Nigerian local dogs

2017 ◽  
Vol 90 (1) ◽  
Author(s):  
Solomon Ajibola ◽  
Johnson Oyewale ◽  
Bankole Oke ◽  
Ladoke Durotoye ◽  
Timothy Adeliyi ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Wall Thickness ◽  
Posterior Wall ◽  
Left Ventricular ◽  
Internal Diameter ◽  
Systolic Volume ◽  
Posterior Wall Thickness ◽  
Septal Wall Thickness ◽  
End Systolic Volume ◽  
Healthy Dogs

There are currently no reported cardiac indices for the Nigerian dog. The aim of the study was to obtain breed specific echocardiographic indices for Nigerian local dogs. M– mode measurements of the left ventricle of 20 healthy dogs were obtained from short axis right parasternal view. The result of the study showed that posterior wall thickness in diastole and systole (PWTd, PWTs), septal wall thickness in diastole and systole (SWTd, SWTs), and left ventricular internal diameter in diastole and systole (LVIDd LVIDs) were positively and significantly correlated with body weight. Except PWT and functional indices like ejection fraction (EF) and fractional shortening (FS) whose values were higher than some breeds in literature, all other indices were within the range of values obtained in breeds previously studied. There was no significant correlation between PWTd PWTs, SWTd, SWTs and cardiac function indices such as EF, FS, enddiastolic volume (EDV), end- systolic volume (ESV) and stroke volume (SV). Although LVIDd had positive correlation with EDV, ESV, and SV, it did not correlate with FS and EF. The study revealed that cardiac function indices like FS and EF are not dependent on septal and wall thickness but rather on ventriclular volume and diameter in systole. Since cardiac function indices are also not dependent on body size, the Nigerian mongrels could serve as a useful model for cardiac studies because of their functional homogenous heart.

scholarly journals The impact of obesity on left ventricular mass and left ventricular systolic function in children

2016 ◽  
Vol 45 (4) ◽  
pp. 171
Author(s):  
Ria Nova ◽  
Bambang Madiyono ◽  
Sudigdo Sastroasmoro ◽  
Damayanti R Sjarif
Keyword(s):  
Wall Thickness ◽  
Systolic Function ◽  
Posterior Wall ◽  
Left Ventricular ◽  
Internal Diameter ◽  
Obese Children ◽  
Normal Children ◽  
Posterior Wall Thickness ◽  
Lv Mass ◽  
Lv Systolic Function

Background Obesity causes cardiovascular disturbances. Theincidence of cardiovascular disease is higher even in mildly obesepatients than in lean subjects.Objectives The purpose of this study was to compare left ven-tricular (LV) mass, LV internal dimensions, and LV systolic func-tion between obese and normal children; and to determine the as-sociation of the degree of obesity with LV mass and LV systolicfunction.Methods This cross-sectional study was conducted on elemen-tary school students in Jakarta from February to April 2003. Wemeasured the subjects’ body weight and height, and performedlipid profile and echocardiography examinations. Measurementsof LV mass, LV internal dimensions with regard to septum thick-ness, LV internal diameter, and LV posterior wall thickness; andLV systolic function as indicated by shortening fraction and ejec-tion fraction, were performed echocardiographically. The differ-ences in measurements between obese and normal children aswell as between obese children with and without lipid abnormalitywere analyzed. The correlation between the degree of obesity withLV size and systolic function was determined.Results Twenty-eight normal children and 62 obese children wereenrolled in the study. Mean LV mass was 35.7 (SD 5.16) g/cm 3 inobese children versus 24.0 (SD 3.80) g/cm 3 in normal children(P<0.0001). Mean septum thickness was 0.8 (SD 0.14) mm inobese children versus 0.6 (SD 7.90) mm in normal children (P<0.0001). Mean posterior wall thickness was 0.9 (SD 0.14) mm inobese children versus 0.6 (SD 9.97) mm in normal children(P<0.0001). Mean LV internal diameter was 4.0 (SD 0.34) mm inobese children versus 3.9 (SD 0.29) mm in normal children(P=0.300). There was strong correlation between the degree ofobesity and LV mass (r=0.838, P<0.0001). LV systolic function(shortening fraction) was 37.1 (SD 4.20) percent in obese childrenversus 35.8 (SD 4.99) percent in normal children (P=0.19). Ejec-tion fraction was 67.4 (SD 5.32) percent in obese children versus65.5 (SD 6.29) percent in normal children (P=0.13). There wasweak correlation between LV systolic function and the degree ofobesity (shortening fraction r=0.219, P=0.038; ejection fractionr=0.239, P=0.023).Conclusions Obese children had significantly greater LV mass,septum thickness, and posterior wall thickness than normal chil-Backgrounddren. Such significant difference was absent for LV internal diam-eter and measures of LV systolic function. There was no signifi-cant difference in LV mass and LV systolic function between obesechildren with or without abnormality of lipid profile. A strong corre-lation exists between the degree of obesity and LV mass, but thecorrelation between degree of obesity and LV systolic function wasweak

scholarly journals Evaluation of azithromycin or hydroxychloroquine plus azithromycin combination therapy on cardiac conduction and function in guinea pigs

2020 ◽  
Author(s):  
Xiang Li ◽  
Weijiang Tan ◽  
Shuang Zheng ◽  
Huan Sun ◽  
Xiaoshen Zhang ◽  
...  
Keyword(s):  
Left Ventricle ◽  
Ejection Fraction ◽  
Cardiac Function ◽  
Wall Thickness ◽  
Guinea Pigs ◽  
Posterior Wall ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Heart Rates ◽  
Posterior Wall Thickness

AbstractBackgroundIn the early stages of the coronavirus disease pandemic, the anti-malarial drug hydroxychloroquine (HCQ) and the antibiotic drug azithromycin (AZM) were widely used as emerging treatments. However, controversial cardiac toxicity results obtained from clinical trials and epidemic studies suggest that the cardiotoxicity of these two drugs should be re-evaluated. In the present study, we aimed to assess the impact of a short course of AZM or HCQ + AZM combination treatment on ECG and cardiac function in healthy guinea pigs.MethodsThirty-two male guinea pigs were randomly divided into four groups: control; AZM; HCQ; and HCQ + AZM groups. At 3, 6, and 9 days after treatment, electrocardiograms (ECGs) and echocardiographic techniques were used to determine important ECG parameters and cardiac functional parameters of the left ventricle (including posterior wall thickness, end systolic/end diastolic volume, ejection fraction, and fractional shortening).ResultsAlthough AZM decreased the heart rates of guinea pigs on day 9 (under anesthetized conditions), HCQ + AZM decreased heart rates on days 3, 6, and 9. The corrected QT intervals of guinea pigs after AZM and HCQ + AZM treatments were significantly increased, compared with CON and HCQ treatment respectively, on days 3, 6, and 9. However, QRS complex durations were not significantly different between the groups. AZM significantly decreased left ventricular ejection fraction (LVEF) and left ventricular fraction shortening (LVFS) on days 3, 6, and 9, whereas HCQ + AZM only decreased LVEF and LVFS on day 9. Posterior wall thickness and of the left ventricle in the diastolic and systolic states were not significantly different between these groups. In addition, compared with CON, AZM and HCQ decreased the EDV. And, in comparison with HCQ treatment, HCQ + AZM treatment increased ESV on day 9.ConclusionsAccording to our study, AZM significantly prolongs the QT interval and damages cardiac function. Moreover, HCQ + AZM treatment increased the risk of cardiac dysfunction compared with HCQ treatment.

Combination of Huangqi Granule and Rosuvastatin Improves the Cardiac Function in Heart Failure

2020 ◽  
Vol 19 (2) ◽  
pp. 181-187
Author(s):  
Jing Li ◽  
Yun Zhang ◽  
Weizhong Huangfu ◽  
Yuhong Ma
Keyword(s):  
Heart Failure ◽  
Left Ventricular Ejection Fraction ◽  
Ejection Fraction ◽  
Wall Thickness ◽  
Posterior Wall ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Model Group ◽  
Ventricular Ejection Fraction ◽  
Posterior Wall Thickness

Using rat models of heart failure, we evaluated the effects of rosuvastatin and Huangqi granule alone and in combination on left ventricular end-diastolic dimension, left ventricular end-systolic dimension, left ventricular ejection fraction, left ventricular posterior wall thickness at end-diastole, and left ventricular posterior wall thickness at end-systole. Results showed that left ventricular end-diastolic dimension, left ventricular end-systolic dimension in the rosuvastatin + Huangqi granule group were significantly decreased (P ‹ 0.01), while left ventricular ejection fraction, left ventricular posterior wall thickness at end-diastole and left ventricular posterior wall thickness at end-systole were significantly increased (P ‹ 0.05). The serum IL-2, IFN-β, and TNF-α in rosuvastatin + Huangqi granule group were significantly lower than those in model group (P ‹ 0.05). However, the levels of S-methylglutathione and superoxide dismutase in rosuvastatin + Huangqi granule group were significantly higher, while nitric oxide was significantly lower than that in the model group (P ‹ 0.05). Also, compared to the model group, the apoptosis rate, and the autophagy protein LC3-II in the cardiomyocytes of rosuvastatin + Huangqi granule group was significantly decreased (P ‹ 0.01), while the level of p62 protein was significantly increased (P ‹ 0.01). The levels of AMPK and p-AMPK in cardiomyocytes were significantly lower in rosuvastatin + Huangqi granule group; however, the levels of mTOR and p-mTOR showed an opposite trend (P ‹ 0.05). To sum up, rosuvastatin + Huangqi granule could improve the cardiac function, decrease the level of oxidative stress, and inflammatory cytokines in rats with HF. The possible underlying mechanism might be inhibition of autophagy and reduced apoptosis in cardiomyocytes by regulating AMPK-mTOR signaling pathway.

Comparison of energy supplements during prolonged exercise for maintenance of cardiac function: carbohydrate only versus carbohydrate plus whey or casein hydrolysate

2016 ◽  
Vol 41 (6) ◽  
pp. 674-683 ◽  
Author(s):  
Tanja Oosthuyse ◽  
Aletta M.E. Millen
Keyword(s):  
Cardiac Function ◽  
Casein Hydrolysate ◽  
Left Ventricular ◽  
Doppler Imaging ◽  
Energy Deficit ◽  
Strenuous Exercise ◽  
Lv Function ◽  
Time Effects ◽  
Systolic Volume ◽  
End Systolic Volume

Cardiac function is often suppressed following prolonged strenuous exercise and this may occur partly because of an energy deficit. This study compared left ventricular (LV) function by 2-dimensional echocardiography and tissue Doppler imaging (TDI) before and after ∼2.5 h of cycling (2-h steady-state 60% peak aerobic power output plus 16 km time trial) in 8 male cyclists when they ingested either placebo, carbohydrate-only (CHO-only), carbohydrate-casein hydrolysate (CHO-casein), or carbohydrate-whey hydrolysate (CHO-whey). No treatment-by-time interactions occurred, but pre-to-postexercise time effects occurred selectively. Although diastolic function measured by pulsed-wave Doppler early-to-late (E/A) transmitral blood flow velocity was suppressed in all trials from pre- to postexercise (mean change post-pre exercise: −0.53 (95% CI −0.15 to −0.91)), TDI early-to-late (e′/a′) tissue velocity was significantly suppressed pre- to postexercise only with placebo, CHO-only, and CHO-whey (septal and lateral wall e′/a′ average change: −0.62 (95% CI −1.12 to −0.12); −0.69 (95% CI −1.19 to −0.20); and −0.79 (95% CI −1.28 to −0.29), respectively) but not with CHO-casein (−0.40 (95% CI −0.90 to 0.09)). LV contractility was, or tended to be, significantly reduced pre- to postexercise with placebo, CHO-only, and CHO-whey (systolic blood pressure/end systolic volume change, mm Hg·mL−1: −0.8 (95% CI −1.2 to −0.4), p = 0.0003; −0.5 (95% CI −0.9 to −0.02), p = 0.035; and −0.4 (95% CI −0.8 to 0.04), p = 0.086, respectively), but not with CHO-casein (−0.3 (95% CI −0.8 to 0.1), p = 0.22). However, ejection fraction (EF) and ventricular-arterial coupling were significantly reduced pre- to postexercise only with placebo (placebo change: EF, −4.6 (95% CI −8.4 to −0.7)%; stroke volume/end systolic volume, −0.3 (95% CI −0.6 to −0.04)). Despite no treatment-by-time interactions, pre-to-postexercise time effects observed with specific beverages may be meaningful for athletes. Tentatively, the order of beverages with least-to-most variables displaying a time effect indicating suppression of LV function following exercise was CHO-casein < CHO-only and CHO-whey < placebo, and calls for further verification.

Anatomical Accuracy of Echocardiographically Assessed Left Ventricular Wall Thickness

1979 ◽  
Vol 57 (s5) ◽  
pp. 55s-57s ◽  
Author(s):  
H. Larkin ◽  
D. C. Johnson ◽  
S. N. Hunyor ◽  
P. Caspari ◽  
R. Kaplan
Keyword(s):  
Direct Measurement ◽  
Wall Thickness ◽  
Posterior Wall ◽  
Left Ventricular ◽  
Left Ventricular Wall ◽  
Ventricular Wall ◽  
Left Ventricular Wall Thickness ◽  
Echocardiographic Measurement ◽  
Posterior Wall Thickness ◽  
Ventricular Wall Thickness

1. A comparison of direct measurement and M-mode echocardiography in the determination of posterior left ventricular wall thickness was performed in 26 subjects, of whom 21 underwent cardiac bypass surgery; the remainder came to necropsy. 2. In the surgical group a close correlation was demonstrated between direct measurement of posterior wall thickness and the echocardiographic end-diastolic dimension (r = 0·76, P &lt; 0·001). 3. The necropsy measurement of posterior wall thickness correlated with the echocardiographic end-systolic dimension (r = 0·99, P &lt; 0·001). 4. These findings confirm that the echocardiographic measurement of posterior wall thickness accurately reflects the anatomical dimension.

scholarly journals Transthyretin amyloid cardiomyopathy in women: frequency, characteristics, and diagnostic challenges

2020 ◽  
Vol 26 (1) ◽  
pp. 35-45 ◽  
Author(s):  
Marianna Bruno ◽  
Adam Castaño ◽  
Arianna Burton ◽  
Justin L. Grodin
Keyword(s):  
Wall Thickness ◽  
Amyloid Fibrils ◽  
Posterior Wall ◽  
Pooled Analysis ◽  
Left Ventricular ◽  
Wild Type ◽  
Eligibility Criteria ◽  
Posterior Wall Thickness ◽  
Life Threatening ◽  
Amyloid Cardiomyopathy

AbstractTransthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive, life-threatening disease characterized by deposition of insoluble amyloid fibrils in the myocardium, resulting in cardiac structural and functional abnormalities and ultimately heart failure. Disease frequency is reportedly lower in women than men, but sex-related differences have not been well established. We conducted a systematic literature review (SLR), based on PRISMA-P guidelines and registered with PROSPERO, to assess whether the epidemiology and clinical presentation of ATTR-CM differ between women and men. MEDLINE, Embase, and Cochrane databases and selected conference proceedings were searched (August 16, 2019) to identify observational and clinical studies reporting sex-specific data for patients with wild-type or hereditary ATTR-CM. Of 193 publications satisfying final eligibility criteria, 69 studies were included in our pooled analysis. Among the 4669 patients with ATTR-CM analyzed, 791 (17%) were women, including 174 (9%), 366 (29%), and 251 (18%) in studies of wild-type, hereditary, and undefined ATTR-CM, respectively. Data available on disease characteristics were limited and very heterogeneous, but trends suggested some cardiac structural/functional differences, i.e., lower interventricular septal and posterior wall thickness and left ventricular (LV) end diastolic diameter, and higher LV ejection fractions, in women versus men across ATTR-CM subtypes. Because LV wall thickness > 12 mm is generally the suggested threshold for ATTR-CM diagnosis in both sexes, smaller cardiac anatomy in women with the disease may lead to underdiagnosis. Additional research and studies are needed to elucidate potential disparities between sexes in ATTR-CM frequency, clinical characteristics, and underlying biological mechanisms. This study was registered within the International Prospective Register of Systematic Reviews (PROSPERO) database of the University of York (CRD42019146995).

P303Prognostic value of diastolic wall strain in patients with asymptomatic severe aortic stenosis

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
Y Suwa ◽  
Y Miyasaka ◽  
N Taniguchi ◽  
S Harada ◽  
I Shiojima
Keyword(s):  
Aortic Valve ◽  
Aortic Stenosis ◽  
Wall Thickness ◽  
Severe Aortic Stenosis ◽  
Posterior Wall ◽  
Left Ventricular ◽  
Aortic Valve Area ◽  
Kaplan Meier ◽  
Posterior Wall Thickness ◽  
Diastolic Wall Strain

Abstract Background Diastolic wall strain (DWS) has been reported to be associated with left ventricular (LV) stiffness and worse clinical outcomes. We sought to assess the utility of this new index for prediction of prognosis in asymptomatic patients with severe aortic stenosis (AS). Methods Asymptomatic severe AS patients [peak flow velocity (PFV) ≥4.0m/s, mean pressure gradient (mPG) ≥40mmHg, aortic valve area (AVA) ≤1.0cm2, or indexed AVA ≤0.6cm2/m2)] diagnosed between July 2007 and April 2016 were included in this study. Patients with significant mitral valve disease, posterior wall motion abnormality, prior cardiac surgery, hypertrophic cardiomyopathy, and LV ejection fraction <50% were excluded. DWS was calculated with a validated formula [DWS = (posterior wall thickness at end-systole − posterior wall thickness at end-diastole)/posterior wall thickness at end-systole]. All study patients were prospectively followed up to last visit or death until November 2017, and predictive value of all-cause death was assessed using Cox-proportional hazards modeling. Patients who underwent aortic valve replacement (AVR) during the study period were censored on the date of surgery. Results A total of 184 asymptomatic severe AS, 138 (age 76±9year-old, men 41%, PFV 3.9±1.0m/s, mPG 38±19mmHg, AVA 0.83±0.18cm2, indexed AVA 0.56±0.13cm2/m2) met all study criteria. Of whom, 43 (31%) underwent AVR and 28 (20%) died during a mean follow-up of 25±28months. In a multivariable model after adjusting for clinical and echocardiographic variables, advancing age (per10yrs; HR=2.19, 95% CI=1.19–4.03, P<0.05), history of hemodialysis (HR=4.31, 95% CI=1.30–14.35, P<0.05), and low-DWS (DWS <0.30) (HR=2.83, 95% CI=1.25–6.40, P<0.05) were independent predictors of all-cause death. In the Kaplan-Meier estimates of cumulative survival stratified by DWS status were shown (Figure). The Kaplan-Meier estimates of survival Conclusion Low-DWS provides prognostic information in patients with asymptomatic severe AS.

Abstract 13770: DWS as an Index of Myocardial Stiffness and a Predictor of Heart Failure Outcome in Patients with Chronic Beta-blockade Therapy

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Yuko Soyama ◽  
Toshiaki Mano ◽  
Shinichi Hirotani ◽  
Mitsuru Masaki ◽  
Miho Fukui ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Wall Thickness ◽  
Posterior Wall ◽  
Left Ventricular ◽  
Beta Blockade ◽  
Myocardial Stiffness ◽  
Reduced Ejection Fraction ◽  
Posterior Wall Thickness ◽  
Diastolic Wall Strain

Background: Diastolic dysfunction determines symptoms and prognosis in patients with left ventricular (LV) dysfunction. Diastolic wall strain (DWS) is associated with poor outcomes in heart failure with preserved ejection fraction. However, the utility of DWS is still unknown in heart failure with reduced ejection fraction (HFrEF). Our aim is to determine whether DWS is predictive of the outcome in HFrEF. Methods: We studied 54 HFrEF patients (LVEF<50%) and followed DWS as an index of myocardial stiffness for 6 months after the induction of beta blockade (Bisoprolol 2.5-10 mg / day). DWS was determined in the LV M-mode echocardiogram using the following equation: DWS = {(LV posterior wall thickness at end-systole - LV posterior wall thickness at end-diastole) / LV posterior wall thickness at end-systole}. We followed for 7years after the induction of beta-blockade. Results: DWS increased after the induction of beta-blockade (0.32±0.11 vs 0.25±0.12,p<0.05). DcT, EF and E’ also increased after the induction of beta-blockade. HR at rest and log BNP decreased following beta blockade. Patients with DWS ≤ median (0.25) before the induction of beta-blockade had higher rate of HF hospitalization than those with DWS >median during 7 years (Log-rank p =0.025). DcT, EF, E’, HR at rest and log BNP before the induction of beta blockade were not significant predictors of HF outcome (Log-rank p=0.263, 0.504, 0.0796, 0.289 and 0.877) respectively. Conclusions: Induction of beta-blockade provided an improvement in DWS. DWS might be useful as an index of myocardial stiffness to predict the outcomes in HFrEF patients with chronic beta-blockade therapy.

Abstract 30: 4-PBA Prevents TAC-induced Myocardial Hypertrophy and Interstitial Fibrosis by Attenuating ER Stress in Mice

2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Tao Luo ◽  
Baihe Chen ◽  
Xianbao Wang
Keyword(s):  
Er Stress ◽  
Therapeutic Effect ◽  
Wall Thickness ◽  
Myocardial Hypertrophy ◽  
Interstitial Fibrosis ◽  
Pressure Overload ◽  
Posterior Wall ◽  
Left Ventricular ◽  
Posterior Wall Thickness ◽  
Imaging Observation

Background: Recently, 4-phenylbutyric acid (4-PBA) has been recognized as a potent ER stress inhibitor and a histone deacetylase inhibitor, but its therapeutic effect in cardiovascular diseases is still not fully understood. Our previous study indicated that attenuation of ER stress by administration of low dosage of 4-PBA (20 mg/kg/d) prevented post-infarction-induced cardiac rupture and remodeling through modulating both cardiac apoptosis and fibrosis in the mouse model of myocardial infarction. However, little is known whether the administration of 4-PBA is effective for hypertrophic heart disease. The aim of this study is therefore to test the therapeutic effect of 4-PBA on pressure-overload induced myocardial hypertrophy. Methods and Results: Transverse aortic constriction (TAC) was used to produce pressure-overload in C57BL/6 male mice for 4 weeks. After surgery, 4-PBA (20mg/kg/d) or 0.9% NaCL was intraperitoneally injected daily. At the end of 4 weeks, the survivals were underwent high-resolution echocardiographic imaging observation. The results showed that the left ventricular posterior wall thickness at end systole (LVPWs) and left ventricular posterior wall thickness at end diastole (LVPWd) were increased in TAC group. Administration of 4-PBA ameliorated this hypertrophic effect. Autopsy also confirmed the anti-hypertrophic effect of 4-PBA. Masson-staining found that there was no difference in perivascular fibrosis between TAC and TAC+4-PBA groups. However, myocardial interstitial fibrosis and collagen deposition were significant decreased by 4-PBA. We finally detected the ER stress and histone acetylation using western blotting. Our results showed that 4-PBA, at the dosage of 20 mg/kg/day, decreased the expression of CHOP and had no effect on histone 3 acetylation. Conclusion: These findings indicate that attenuating ER stress by 4-PBA maybe a promising therapeutic strategy to prevent pressure-overload induced myocardial hypertrophy and interstitial fibrosis.

scholarly journals Chronic Treatment with Multi-Kinase Inhibitors Causes Differential Toxicities on Skeletal and Cardiac Muscles

Cancers ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 571 ◽  
Author(s):  
Joshua R. Huot ◽  
Alyson L. Essex ◽  
Maya Gutierrez ◽  
Rafael Barreto ◽  
Meijing Wang ◽  
...  
Keyword(s):  
Cardiac Muscle ◽  
Muscle Mass ◽  
Molecular Mechanisms ◽  
Kinase Inhibitors ◽  
Chronic Administration ◽  
Posterior Wall ◽  
Left Ventricular ◽  
Internal Diameter ◽  
Posterior Wall Thickness

Despite recent progress, chemotherapy remains the preferred treatment for cancer. We have shown a link between anticancer drugs and the development of cachexia, i.e., body wasting accompanied by muscle loss. The multi-kinase inhibitors (MKIs) regorafenib and sorafenib, used as second-line treatment for solid tumors, are frequently accompanied by several side effects, including loss of muscle mass and strength. In the present study we aimed to investigate the molecular mechanisms associated with the occurrence of muscle toxicities in in vivo conditions. Hence, we treated 8-week old healthy CD2F1 male mice with MKIs for up to six weeks and observed decreased skeletal and cardiac muscle mass, consistent with muscle weakness. Modulation of ERK1/2 and GSK3β, as well as increased expression of markers of autophagy, previously associated with muscle atrophy conditions, were shown in skeletal muscle upon treatment with either drug. MKIs also promoted cardiac abnormalities consistent with reduced left ventricular mass, internal diameter, posterior wall thickness and stroke volume, despite unchanged overall function. Notably, different signaling pathways were affected in the heart, including reduced expression of mitochondrial proteins, and elevated AKT, GSK3β, mTOR, MEK1/2 and ERK1/2 phosphorylation. Combined, our data demonstrate detrimental effects on skeletal and cardiac muscle in association with chronic administration of MKIs, although different mechanisms would seem to contribute to the cachectic phenotype in the two tissues.

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