Lost in translation: Interpreting cardiac muscle mechanics data in clinical practice
| Autor: | Ranganath Mamidi, Joshua B Holmes, Jiayang Li, Julian E. Stelzer, Chang Yoon Doh |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Inotrope Sarcomeres Cardiotonic Agents Biophysics Biochemistry Sarcomere Article Contractility Translational Research Biomedical 03 medical and health sciences Myosin medicine Myocyte Animals Humans Molecular Biology Heart Failure 030102 biochemistry & molecular biology business.industry Myocardium Cardiac muscle medicine.disease Myocardial Contraction 030104 developmental biology medicine.anatomical_structure Heart failure business Neuroscience Intracellular |
| Zdroj: | Archives of biochemistry and biophysics. 662 |
| ISSN: | 1096-0384 |
| Popis: | Current inotropic therapies improve systolic function in heart failure patients but they also elicit undesirable side effects such as arrhythmias and increased intracellular Ca(2+) transients. In order to maintain myocyte Ca(2+) homeostasis, the increased cytosolic Ca(2+) needs to be actively transported back to sarcoplasmic reticulum leading to depleted ATP reserves. Thus, an emerging approach is to design sarcomere-based treatments to correct impaired contractility via a direct and allosteric modulation of myosin’s intrinsic force-generating behavior –a concept that potentially avoids the “off-target” effects. To achieve this goal, various biophysical approaches are utilized to investigate the mechanistic impact of sarcomeric modulators but information derived from diverse approaches is not fully integrated into therapeutic applications. This is in part due to the lack of information that provides a coherent connecting link between biophysical data to in vivo function. Hence, our ability to clearly discern the drug-mediated impact on whole-heart function is diminished. Reducing this translational barrier can significantly accelerate clinical progress related to sarcomere-based therapies by optimizing drug-dosing and treatment duration protocols based on information obtained from biophysical studies. Therefore, we attempt to link biophysical mechanical measurements obtained in isolated cardiac muscle and in vivo contractile function. |
| Databáze: | OpenAIRE |
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