scholarly journals Differences in cardioprotective efficacy of adrenergic receptor antagonists and Ca2+ channel antagonists in an animal model of dilated cardiomyopathy. Effects on gross morphology, global cardiac function, and twitch force.

1993 ◽  
Vol 73 (6) ◽  
pp. 1077-1089 ◽  
Author(s):  
M G Glass ◽  
F Fuleihan ◽  
R Liao ◽  
A M Lincoff ◽  
R Chapados ◽  
...  
Keyword(s):  
Animal Model ◽  
Cardiac Function ◽  
Dilated Cardiomyopathy ◽  
Adrenergic Receptor ◽  
Receptor Antagonists ◽  
Twitch Force ◽  
Global Cardiac Function

scholarly journals Doberman pinschers present autoimmunity associated with functional autoantibodies: a model to study the autoimmune background of human dilated cardiomyopathy

2019 ◽  
Author(s):  
Gerhard Wess ◽  
Gerd Wallukat ◽  
Anna Fritscher ◽  
Niels-Peter Becker ◽  
Katrin Wenzel ◽  
...  
Keyword(s):  
Animal Model ◽  
Animal Models ◽  
Dilated Cardiomyopathy ◽  
Adrenergic Receptor ◽  
Treatment Strategies ◽  
Healthy Controls ◽  
Receptor Binding Site ◽  
Doberman Pinschers ◽  
Overall Mortality

AbstractBackgroundAutoimmunity associated with autoantibodies directed against the β1-adrenergic receptor (β1-AAB) is increasingly accepted as driving human dilated cardiomyopathy (DCM). Unfortunately, animal models of DCM are lacking, preventing our knowledge about β1-AAB autoimmunity in DCM from being extended and hindering the development of related treatment strategies.ObjectivesTo introduce an animal model, we studied Doberman pinschers, which develop cardiomyopathy (DoCM), with similarities to human DCM, with regard to their β1-AAB autoimmunity.MethodsEighty-seven DP with DoCM and 31 (at enrolment) healthy controls were analyzed for β1-AAB; the receptor binding site and sensitivity to inhibition were determined. In controls who developed cardiomyopathy during the follow-up, β1-AAB were analyzed during the DoCM progress.ResultsFifty-nine (67.8%) DoCM dogs and 19 (61.3%) controls were β1-AAB positive. Excluding the 9 controls who developed DoCM in the follow-up, β1-AAB positivity tended to be more pronounced in DoCM.From the controls who developed DoCM, 8 were β1-AAB positive (p=0.044 vs. dogs remaining healthy); their β1-AAB level increased with the cardiomyopathy progress. Overall mortality and mortality exclusively due to cardiac reasons during the study period, were higher (p=0.002; p=0037) in β1-AAB positive dogs. The dogs’ β1-AAB targeted a specific epitope centralized on the second extracellular receptor and were sensitive to inhibition by drugs already successful tested for the corresponding human autoantibody.ConclusionsDoberman pinschers presented β1-AAB associated autoimmunity similar to that driving the pathogenesis of human DCM. Consequently, DP could remove the lack of animal models available for studying β1-AAB autoimmunity in DCM.

scholarly journals Up-regulating autophagy by targeting the mTOR-4EBP1 pathway: a possible mechanism for improving cardiac function in mice with experimental dilated cardiomyopathy

2020 ◽  
Author(s):  
Bo Jin ◽  
Haiming Shi ◽  
Zhu Jun ◽  
Bangwei Wu ◽  
Quzhen Geshang
Keyword(s):  
Animal Model ◽  
Cardiovascular Diseases ◽  
Cardiac Function ◽  
Dilated Cardiomyopathy ◽  
Cardiac Remodeling ◽  
Therapeutic Strategy ◽  
Volume Fraction ◽  
Pathological Process ◽  
Cardiac Myosin ◽  
Pathological Mechanism

Abstract Background: Autophagy plays a crucial role in the pathological process of cardiovascular diseases. However, little is known about the pathological mechanism underlying autophagy regulation in dilated cardiomyopathy (DCM). Methods: We explored whether up-regulating autophagy could improve cardiac function in mice with experimental DCM through the mTOR-4EBP1 pathway. Animal model of DCM was established in BALB/c mice by immunization with porcine cardiac myosin. Both up- or down-regulation of autophagy were studied by administration of rapamycin or 3-MA in parallel. Morphology, Western blotting, and echocardiography were applied to confirm the pathological mechanisms. Results: Autophagy was activated and autophagosomes were significantly increased in the rapamycin group. The collagen volume fraction (CVF) was decreased in the rapamycin group compared with the DCM group (9.21 ± 0.82 % vs 14.38 ± 1.24 %, P<0.01). The expression of p-mTOR and p-4EBP1 were significantly decreased in rapamycin-induced autophagy activation, while the levels were increased by down-regulating autophagy with 3-MA. In the rapamycin group, the LVEF and FS were significantly increased compared with the DCM group (54.12 ± 6.48 % vs 45.29 ± 6.68 %, P <0.01; 26.89 ± 4.04 % vs 22.17 ± 2.82 %, P <0.05). As the inhibitor of autophagy, 3-MA aggravated the progress of maladaptive cardiac remodeling and declined cardiac function in DCM mice. Conclusions: The study indicated a possible mechanism for improving cardiac function in mice with experimental DCM by up-regulating autophagy via the mTOR-4EBP1 pathway, which could be a promising therapeutic strategy for DCM.

scholarly journals Up-regulating autophagy by targeting the mTOR-4EBP1 pathway: a possible mechanism for improving cardiac function in mice with experimental dilated cardiomyopathy

2019 ◽  
Author(s):  
Bo Jin ◽  
Haiming Shi ◽  
Zhu Jun ◽  
Bangwei Wu ◽  
Quzhen Geshang
Keyword(s):  
Animal Model ◽  
Cardiovascular Diseases ◽  
Cardiac Function ◽  
Dilated Cardiomyopathy ◽  
Cardiac Remodeling ◽  
Therapeutic Strategy ◽  
Volume Fraction ◽  
Pathological Process ◽  
Cardiac Myosin ◽  
Pathological Mechanism

Abstract Background: Autophagy plays a crucial role in the pathological process of cardiovascular diseases. However, little is known about the pathological mechanism underlying autophagy regulation in dilated cardiomyopathy (DCM).Methods: We explored whether up-regulating autophagy could improve cardiac function in mice with experimental DCM through the mTOR-4EBP1 pathway. Animal model of DCM was established in BALB/c mice by immunization with porcine cardiac myosin. Both up- or down-regulation of autophagy were studied by administration of rapamycin or 3-MA in parallel. Morphology, Western blotting, and echocardiography were applied to confirm the pathological mechanisms.Results: Autophagy was activated and autophagosomes were significantly increased in the rapamycin group. The collagen volume fraction (CVF) was decreased in the rapamycin group compared with the DCM group (9.21 ± 0.82 % vs 14.38 ± 1.24 %, P<0.01). The expression of p-mTOR and p-4EBP1 were significantly decreased in rapamycin-induced autophagy activation, while the levels were increased by down-regulating autophagy with 3-MA. In the rapamycin group, the LVEF and FS were significantly increased compared with the DCM group (54.12 ± 6.48 % vs 45.29 ± 6.68 %, P<0.01; 26.89 ± 4.04 % vs 22.17 ± 2.82 %, P<0.05). As the inhibitor of autophagy, 3-MA aggravated the progress of maladaptive cardiac remodeling and declined cardiac function in DCM mice.Conclusions: The study indicated a possible mechanism for improving cardiac function in mice with experimental DCM by up-regulating autophagy via the mTOR-4EBP1 pathway, which could be a promising therapeutic strategy for DCM.

scholarly journals Up-regulating autophagy by targeting the mTOR-4EBP1 pathway: a possible mechanism for improving cardiac function in mice with experimental dilated cardiomyopathy

2020 ◽  
Author(s):  
Bo Jin ◽  
Haiming Shi ◽  
Zhu Jun ◽  
Bangwei Wu ◽  
Quzhen Geshang
Keyword(s):  
Animal Model ◽  
Cardiovascular Diseases ◽  
Cardiac Function ◽  
Dilated Cardiomyopathy ◽  
Cardiac Remodeling ◽  
Therapeutic Strategy ◽  
Volume Fraction ◽  
Pathological Process ◽  
Cardiac Myosin ◽  
Pathological Mechanism

Abstract Background: Autophagy plays a crucial role in the pathological process of cardiovascular diseases. However, little is known about the pathological mechanism underlying autophagy regulation in dilated cardiomyopathy (DCM).Methods: We explored whether up-regulating autophagy could improve cardiac function in mice with experimental DCM through the mTOR-4EBP1 pathway. Animal model of DCM was established in BALB/c mice by immunization with porcine cardiac myosin. Both up- or down-regulation of autophagy were studied by administration of rapamycin or 3-MA in parallel. Morphology, Western blotting, and echocardiography were applied to confirm the pathological mechanisms.Results: Autophagy was activated and autophagosomes were significantly increased in the rapamycin group. The collagen volume fraction (CVF) was decreased in the rapamycin group compared with the DCM group (9.21 ± 0.82 % vs 14.38 ± 1.24 %, P<0.01). The expression of p-mTOR and p-4EBP1 were significantly decreased in rapamycin-induced autophagy activation, while the levels were increased by down-regulating autophagy with 3-MA. In the rapamycin group, the LVEF and FS were significantly increased compared with the DCM group (54.12 ± 6.48 % vs 45.29 ± 6.68 %, P<0.01; 26.89 ± 4.04 % vs 22.17 ± 2.82 %, P<0.05). As the inhibitor of autophagy, 3-MA aggravated the progress of maladaptive cardiac remodeling and declined cardiac function in DCM mice.Conclusions: The study indicated a possible mechanism for improving cardiac function in mice with experimental DCM by up-regulating autophagy via the mTOR-4EBP1 pathway, which could be a promising therapeutic strategy for DCM.

Ligand and Structure Based Models for the Identification of Beta 2 Adrenergic Receptor Antagonists

2015 ◽  
Vol 11 (3) ◽  
pp. 222-236 ◽  
Author(s):  
Jayadev Joshi ◽  
Manali Dimri ◽  
Subhajit Ghosh ◽  
Nitisha Shrivastava ◽  
Rina Chakraborti ◽  
...  
Keyword(s):  
Adrenergic Receptor ◽  
Receptor Antagonists ◽  
Beta 2

Heart rate as a marker of relapse during withdrawal of heart failure therapy in patients with recovered dilated cardiomyopathy: an analysis from TRED-HF

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
B Halliday ◽  
A Vazir ◽  
R Owen ◽  
J Gregson ◽  
R Wassall ◽  
...  
Keyword(s):  
Heart Rate ◽  
Cardiac Function ◽  
Dilated Cardiomyopathy ◽  
Funding Source ◽  
End Point ◽  
Therapy Withdrawal ◽  
The Mean ◽  
Withdrawal Of Therapy ◽  
Continue Therapy

Abstract Introduction In TRED-HF, 40% of patients with recovered dilated cardiomyopathy (DCM) relapsed in the short-term during phased withdrawal of drug therapy. Non-invasive markers of relapse may be used to monitor patients who wish a trial of therapy withdrawal and provide insights into the pathophysiological drivers of relapse. Purpose To investigate the relationship between changes in heart rate (HR) and relapse amongst patients with recovered DCM undergoing therapy withdrawal in TRED-HF. Methods Patients with recovered DCM were randomised to phased withdrawal of therapy or to continue therapy for 6 months. After 6 months of continued therapy, those in the control arm underwent withdrawal of therapy in a single arm crossover phase. HR was measured at each study visit. Mean HR and 95% confidence intervals (CI) were calculated at baseline, 45 days after baseline, 45 days prior to the end of the study or relapse and at the end of the study or relapse. Patients were stratified by treatment arm and the occurrence of the primary relapse end-point. Heart rate at follow-up was compared amongst patients who had therapy withdrawn and relapsed versus those who had therapy withdrawn and did not. ANCOVA was used to adjust for differences in HR at baseline between the two groups. Results Of 51 patients randomised, 26 were assigned to continue therapy and 25 to withdraw therapy. In the randomised and cross-over phases, 20 patients met the primary relapse end-point; one patient withdrew from the study and one patient completed follow-up in the control arm but did not enter the cross-over phase. Mean HR (standard deviation) at baseline and follow-up for (i) patients in the control arm was 69.9 (9.8) & 65.9 (9.1) respectively; (ii) for those who had therapy withdrawn and did not relapse was 64.6 (10.7) & 74.7 (10.4) respectively; and (iii) for those who had therapy withdrawn and relapsed was 68.3 (11.3) & 86.1 (11.8) respectively [all beats per minute]. The mean change in HR between the penultimate visit and the final visit for those who had therapy withdrawn and did not relapse was −2.4 (9.7) compared to 3.1 (15.5) for those who relapsed. After adjusting for differences in HR at baseline, the mean difference in HR measured at follow-up between patients who underwent therapy withdrawal and did, and did not relapse was 10.4bpm (95% CI 4.0–16.8; p=0.002) (Figure 1 & Table 1). Conclusion(s) A larger increase in HR may be a simple and effective marker of relapse for patients with recovered DCM who have insisted on a trial of therapy withdrawal. Whether HR control is crucial to the maintenance of remission amongst patients with improved cardiac function, or is simply a marker of deteriorating cardiac function, warrants further investigation. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): British Heart Foundation

Sign in / Sign up

Export Citation Format

Share Document