Severe dilated cardiomyopathy was associated with a longer period of sarcomeric auto-oscillations and prolonged shortening time compared to nonfailing myofibrils.
Observational
Does troponin exchange normalize sarcomere dynamics in myofibrils from patients with severe dilated cardiomyopathy?
Depressed sarcomere dynamics in dilated cardiomyopathy myofibrils are caused by impaired thick-thin filament sliding, which can be normalized by troponin exchange.
Background: Left ventricular wall motion is depressed in patients with dilated cardiomyopathy (DCM). However, whether or not the depressed left ventricular wall motion is caused by impairment of sarcomere dynamics remains to be fully clarified. Methods and Results: We analyzed the mechanical properties of single sarcomere dynamics during sarcomeric auto-oscillations (calcium spontaneous oscillatory contractions Ca-SPOC) that occurred at partial activation under the isometric condition in myofibrils from donor hearts and from patients with severe DCM (New York Heart Association classification III-IV). Ca-SPOC reproducibly occurred in the presence of 1 μmol/L free Ca 2+ in both nonfailing and DCM myofibrils, and sarcomeres exhibited a saw-tooth waveform along single myofibrils composed of quick lengthening and slow shortening. The period of Ca-SPOC was longer in DCM myofibrils than in nonfailing myofibrils, in association with prolonged shortening time. Lengthening time was similar in both groups. Then, we performed Tn (troponin) exchange in myofibrils with a DCM-causing homozygous mutation (K36Q) in cTnI (cardiac TnI). On exchange with the Tn complex from healthy porcine ventricles, period, shortening time, and shortening velocity in cTnI-K36Q myofibrils became similar to those in Tn-reconstituted nonfailing myofibrils. Protein kinase A abbreviated period in both Tn-reconstituted nonfailing and cTnI-K36Q myofibrils, demonstrating acceleration of cross-bridge kinetics. Conclusions: Sarcomere dynamics was found to be depressed under loaded conditions in DCM myofibrils because of impairment of thick-thin filament sliding. Thus, microscopic analysis of Ca-SPOC in human cardiac myofibrils is beneficial to systematically unveil the kinetic properties of single sarcomeres in various types of heart disease.
Kagemoto et al. (Sun,) conducted a observational in Dilated Cardiomyopathy. Severe dilated cardiomyopathy vs. Nonfailing donor hearts was evaluated on Mechanical properties of single sarcomere dynamics during sarcomeric auto-oscillations (Ca-SPOC). Severe dilated cardiomyopathy was associated with a longer period of sarcomeric auto-oscillations and prolonged shortening time compared to nonfailing myofibrils.