Cardiac myosin binding protein-C is a potential diagnostic biomarker for myocardial infarction.

Cardiac myosin binding protein-C (cMyBP-C) is a thick filament assembly protein that stabilizes sarcomeric structure and regulates cardiac function; however, the profile of cMyBP-C degradation after myocardial infarction (MI) is unknown. We hypothesized that cMyBP-C is sensitive to proteolysis and is specifically increased in the bloodstream post-MI in rats and humans. Under these circumstances, elevated levels of degraded cMyBP-C could be used as a diagnostic tool to confirm MI. To test this hypothesis, we first established that cMyBP-C dephosphorylation is directly associated with increased degradation of this myofilament protein, leading to its release in vitro. Using neonatal rat ventricular cardiomyocytes in vitro, we were able to correlate the induction of hypoxic stress with increased cMyBP-C dephosphorylation, degradation, and the specific release of N'-fragments. Next, to define the proteolytic pattern of cMyBP-C post-MI, the left anterior descending coronary artery was ligated in adult male rats. Degradation of cMyBP-C was confirmed by a reduction in total cMyBP-C and the presence of degradation products in the infarct tissue. Phosphorylation levels of cMyBP-C were greatly reduced in ischemic areas of the MI heart compared to non-ischemic regions and sham control hearts. Post-MI plasma samples from these rats, as well as humans, were assayed for cMyBP-C and its fragments by sandwich ELISA and immunoprecipitation analyses. Results showed significantly elevated levels of cMyBP-C in the plasma of all post-MI samples. Overall, this study suggests that cMyBP-C is an easily releasable myofilament protein that is dephosphorylated, degraded and released into the circulation post-MI. The presence of elevated levels of cMyBP-C in the blood provides a promising novel biomarker able to accurately rule in MI, thus aiding in the further assessment of ischemic heart disease.

Novel approach to admittance to volume conversion for ventricular volume measurement.

The conductance catheter is a widely used tool to determine ventricular volumes in animal models. A tetra-polar catheter is inserted into the ventricle to measure instantaneous conductance, which is a combination of ventricular blood and surrounding myocardium. Various techniques have been used to separate the blood conductance signal from the combined measured signal [1], [2]. The blood conductance is then converted to volume using a linear relationship proposed by Baan [1] or an improved non linear relationship proposed by Wei [3]. We propose a novel approach that uses the combined blood-muscle signal to calculate volume, thereby eliminating the need to subtract out the muscle. In vivo experiments were performed in mice to validate this new approach and the results were compared with volumes obtained using ultrasound imaging.