Effect of Clenbuterol on Cardiac and Skeletal Muscle Function During Left Ventricular Assist Device Support

George, Isaac; Xydas, Steve; Mancini, Donna; LaManca, John J.; DiTullio, Marco R.; Marboe, Charles C.; Shane, Elizabeth; Schulman, Allison R.; Colley, Patrick; Petrilli, Christopher M.; Naka, Yoshifumi; Öz, Mehmet C.; Maybaum, Simon

doi:10.1016/j.healun.2006.06.017

Cited by 49 publications

(34 citation statements)

References 20 publications

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“…Additionally, clenbuterol, used in conjunction with LV assistant devices, promotes reverse remodelling (Soppa et al, 2005;. Moreover, adjuvant treatment of HF patients with clenbuterol along with bisoprolol, a selective β1-adrenoceptor antagonist, improved myocardial recovery, thus supporting the idea that selective stimulation of β2-adrenoceptors might be protective for the failing myocardium (George et al, 2006).…”

Section: Discussionmentioning

confidence: 93%

Effects of chronic treatment with the new ultra‐long‐acting β₂‐adrenoceptor agonist indacaterol alone or in combination with the β₁‐adrenoceptor blocker metoprolol on cardiac remodelling

Rinaldi

Donniacuo

Sodano

et al. 2015

British J Pharmacology

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BACKGROUND AND PURPOSEThe ability of a chronic treatment with indacaterol, a new ultra-long-acting β2-adrenoceptor agonist, to reverse cardiac remodelling and its effects in combination with metoprolol, a selective β1-adrenoceptor antagonist, were investigated on myocardial infarction in a rat model of heart failure (HF). EXPERIMENTAL APPROACHWe investigated the effects of indacaterol and metoprolol, administered alone or in combination, on myocardial histology, β-adrenoceptor-mediated pathways, markers of remodelling and haemodynamic parameters in a rat model of HF. Five groups of rats were assessed: sham-operated rats; HF rats; HF + indacaterol 0.3 mg·kg ; HF + metoprolol + indacaterol. All pharmacological treatments continued for 15 weeks. KEY RESULTSTreatment with either indacaterol or metoprolol significantly reduced the infarct size in HF rats. However, the combination of indacaterol and metoprolol reduced the infarct size even further, reduced both BP and heart rate, reversed the decrease in ejection fraction, normalized left ventricular systolic and diastolic internal diameters, normalized the decreased β1 adrenoceptor mRNA expression as well as cardiac cAMP levels and reduced cardiac GPCR kinase 2 expression, compared with the untreated HF group. CONCLUSION AND IMPLICATIONSThe results of our study demonstrated an additive interaction between indacaterol and metoprolol in normalizing and reversing cardiac remodelling in our experimental model of HF. The translation of these findings to clinical practice might be of interest, as this combination of drugs could be safer and more effective in patients suffering from HF and COPD. AbbreviationsANP, atrial natriuretic peptide; BNP, brain natriuretic peptide; EF, ejection fraction (%); GRK2, GPCR kinase 2; HF, heart failure; LV, left ventricular; LVIDd, LV diastolic internal diameter; LVIDs, LV systolic internal diameter

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Section: Discussionmentioning

confidence: 93%

Effects of chronic treatment with the new ultra‐long‐acting β₂‐adrenoceptor agonist indacaterol alone or in combination with the β₁‐adrenoceptor blocker metoprolol on cardiac remodelling

Rinaldi

Donniacuo

Sodano

et al. 2015

British J Pharmacology

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“…Clenbuterol is also known for enhancing regeneration of peripheral nerves in rodents (13,44), for inducing redistribution of white blood cells in the circulation (33), and decreasing body fat (46). Chronic clenbuterol administration is known to produce skeletal (16) and cardiac hypertrophy and to affect excitationcontraction coupling and cellular metabolism (34), gene expression, and myocardial function (27,36,37) in normal hearts. Clenbuterol treatment during mechanical unloading of normal hearts improves ␤-AR responsiveness and gene expression [sarco(endo)plasmic reticulum Ca 2ϩ -ATPase 2a and ␤-myosin heavy chain] and reduces myocardial apoptosis (35).…”

mentioning

confidence: 99%

Effects of clenbuterol on contractility and Ca²⁺ homeostasis of isolated rat ventricular myocytes

Siedlecka

Arora²,

Kolettis³

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

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“…Our choice of Cl was motivated by work published by others, which show left ventricle hypertrophy and possibly a revival of the myocardium in patients on left ventricular assist devices in response to clenbuterol administration. 16,22,42,49 Utilization of physiological found candidates would certainly be more desirable, and hence IGF-1 was targeted for further studies. In follow up studies in our laboratory, we have added thyroid hormone as another candidate.…”

Section: Discussionmentioning

confidence: 99%

Modulating the Functional Performance of Bioengineered Heart Muscle Using Growth Factor Stimulation

2008

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Congestive heart failure (CHF) is a major medical challenge in developed countries. The field of cardiac tissue engineering may provide alternative treatment methods of CHF to current surgical and pharmacological therapies. We previously described a model for the formation of Bioengineered Heart Muscle (BEHM), using fibrin gel as a support matrix for primary cardiac cells during 3D construct formation. In the current study, we describe modulating the contractile properties of BEHMs utilizing clenbuterol, insulin like growth factor-1 (IGF-1), and thyroid hormone (T3), as additive factors to primary cardiac cells. We found significant changes in force production with the addition of clenbuterol (control: 95.0 +/- 32.9 microN, clenbuterol: 201.0 +/- 15.8 microN) and IGF-1 (control: 202.9 +/- 18 microN, IGF-1: 272.6 +/- 19.5 microN) was seen. Selecting IGF-1-treated BEHMs for further analysis, we found an increase in force production during extended culturing at 7, 14 days. Also, at 25 ng/mL, myosin heavy chain alpha and SERCA2 expression increased by 1.3 +/- 0.188 and 1.1 +/- 0.04 fold, respectively. Our findings provide preliminary data that can be used to produce BEHMs with higher force of contraction. Exposing BEHMs to these factors would condition the engineered muscle for possible implantation onto injured hearts without cell shock.

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Effect of Clenbuterol on Cardiac and Skeletal Muscle Function During Left Ventricular Assist Device Support

Cited by 49 publications

References 20 publications

Effects of chronic treatment with the new ultra‐long‐acting β₂‐adrenoceptor agonist indacaterol alone or in combination with the β₁‐adrenoceptor blocker metoprolol on cardiac remodelling

Effects of chronic treatment with the new ultra‐long‐acting β₂‐adrenoceptor agonist indacaterol alone or in combination with the β₁‐adrenoceptor blocker metoprolol on cardiac remodelling

Effects of clenbuterol on contractility and Ca²⁺ homeostasis of isolated rat ventricular myocytes

Modulating the Functional Performance of Bioengineered Heart Muscle Using Growth Factor Stimulation

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Effect of Clenbuterol on Cardiac and Skeletal Muscle Function During Left Ventricular Assist Device Support

Cited by 49 publications

References 20 publications

Effects of chronic treatment with the new ultra‐long‐acting β2‐adrenoceptor agonist indacaterol alone or in combination with the β1‐adrenoceptor blocker metoprolol on cardiac remodelling

Effects of chronic treatment with the new ultra‐long‐acting β2‐adrenoceptor agonist indacaterol alone or in combination with the β1‐adrenoceptor blocker metoprolol on cardiac remodelling

Effects of clenbuterol on contractility and Ca2+ homeostasis of isolated rat ventricular myocytes

Modulating the Functional Performance of Bioengineered Heart Muscle Using Growth Factor Stimulation

Contact Info

Product

Resources

About

Effects of chronic treatment with the new ultra‐long‐acting β₂‐adrenoceptor agonist indacaterol alone or in combination with the β₁‐adrenoceptor blocker metoprolol on cardiac remodelling

Effects of chronic treatment with the new ultra‐long‐acting β₂‐adrenoceptor agonist indacaterol alone or in combination with the β₁‐adrenoceptor blocker metoprolol on cardiac remodelling

Effects of clenbuterol on contractility and Ca²⁺ homeostasis of isolated rat ventricular myocytes