Ryanodine receptors mediate high intracellular Ca2+ and some myocyte damage following eccentric contractions in rat fast twitch skeletal muscle

Eccentric contractions (ECC) facilitate cytosolic calcium ion (Ca2+) release from the sarcoplasmic reticulum (SR) and Ca2+ influx from extracellular space. Ca2+ is a vital signaling messenger that regulates multiple cellular processes via its spatial and temporal concentration ([Ca2+]i) dynamics. We hypothesized that: 1) a specific pattern of spatial/temporal intramyocyte Ca2+ dynamics portends muscle damage following ECC, and 2) these dynamics would be regulated by the ryanodine receptor (RyR). [Ca2+]i in the tibialis anterior muscles of anesthetized adult Wistar rats was measured by ratiometric (i.e. ratio, R, 340/380 nm excitation) in vivo bioimaging with Fura-2 pre-ECC and at 5 and 24 hours post-ECC (5 x 40 contractions). Rats received RyR inhibitor dantrolene (DAN; 10 mg/kg i.p.) immediately post-ECC (+DAN). Muscle damage was evaluated by histological analysis on hematoxylin-eosin stained muscle sections. Compared to control (CONT, no ECC), [Ca2+]i distribution was heterogeneous with increased % total area of high [Ca2+]i sites (operationally defined as R > 1.39 i.e., > 1 SD of mean control) 5 hours post-ECC (CONT, 14.0 ± 8.0; ECC5h: 52.0 ± 7.4%, p < 0.01). DAN substantially reduced the high [Ca2+]i area 5 hours post-ECC (ECC5h+DAN: 6.4 ± 3.1%, p < 0.01) and myocyte damage (ECC24h, 63.2 ± 1.0%; ECC24h+DAN, 29.1 ± 2.2%, p < 0.01). Temporal and spatially-amplified [Ca2+]i fluctuations occurred regardless of DAN (ECC vs ECC+DAN, p > 0.05). These results suggest that the RyR-mediated local high [Ca2+]i itself is related to the magnitude of muscle damage while the [Ca2+]i fluctuation is an RyR-independent phenomenon.

MicroRNAs as Biomarkers of Systemic Changes in Response to Endurance Exercise—A Comprehensive Review

Endurance sports have an unarguably beneficial influence on cardiovascular health and general fitness. Regular physical activity is considered one of the most powerful tools in the prevention of cardiovascular disease. MicroRNAs are small particles that regulate the post-transcription gene expression. Previous studies have shown that miRNAs might be promising biomarkers of the systemic changes in response to exercise, before they can be detected by standard imaging or laboratory methods. In this review, we focused on four important physiological processes involved in adaptive changes to various endurance exercises (namely, cardiac hypertrophy, cardiac myocyte damage, fibrosis, and inflammation). Moreover, we discussed miRNAs’ correlation with cardiopulmonary fitness parameter (VO2max). After a detailed literature search, we found that miR-1, miR-133, miR-21, and miR-155 are crucial in adaptive response to exercise.

Myocarditis

Myocarditis can be acute, subacute, or chronic and may affect either focal or diffuse areas of the myocardium. It has many infectious and non-infectious aetiologies, but viral infections are the main cause in most regions, with notable exceptions such as Chagas myocarditis in South America. The condition often results in congestive heart failure and is a common cause of chronic dilated cardiomyopathy, also called inflammatory cardiomyopathy. It can present with (a)typical chest pain, palpitations, ventricular arrhythmias, syncope, or even fulminant heart failure. Patients with lymphocytic myocarditis are usually young (average age in the forties) and often report an antecedent viral illness. The disease can be diagnosed by demonstration of lymphocyte infiltration and adjacent myocyte damage on endomyocardial biopsy, and molecularly by the detection of viral genomic material and tissue markers of immune activation in biopsy specimens.

Measurement of troponin in cardiomyopathies

Troponins are thin myofilament proteins that regulate the contraction of cardiac and skeletal muscle. The cardio-specific troponin I (TnI) and T (TnT) proteins are sensitive and specific biomarkers of myocardial injury which over the past twenty years have revolutionised the diagnosis and management of myocardial infarction. With the advent of high sensitivity assays the role for cardiac troponins is possibly expanding. Elevated levels are associated with adverse cardiovascular events and mortality in heart failure and the general population. Studies in cardiomyopathies are generally small with &lt;200 patients, but serum troponin levels can be chronically raised and detect subclinical myocyte damage. This review examines all major published studies of cardiac troponin measurement in cardiomyopathies. There is considerable variability among studies regarding assays used and definitions of abnormal results but elevated troponin levels are almost invariably related to poor prognosis and their negative predictive value is important.

Beyond the Limits: Clinical Utility of Novel Cardiac Biomarkers

Preoperative assessment of cardiovascular risk is essential when it comes to extensive noncardiac surgery procedures. Therefore, accurate and timely diagnosis of myocyte damage is vital. In modern medical practice it is believed that the so-called “multimarker” approach is the most appropriate and most accurate, but new research points out that there are novel biomarkers which could be used independently. Studies that evaluate miRNA, H-FABP, and MR-PAMP give encouraging results. When it comes to miRNA clinical studies show high statistical significance, especially in the case of acute myocardial infarction (P=0.001). Statistical significance ofP=0.007was found in acute coronary syndrome, when H-FABP was measured. Biochemical marker MR-PAMP showed statistical significance ofP<0.0001in most clinical studies.