Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P21817 (RyR1)
 1,154 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In chronic congestive heart failure (CHF), attenuated heart rate response to exercise, a manifestation of chronotropic incompetence (CI), contributes to limiting exercise capacity. The present study was thus conducted to evaluate the respective role of chronic attenuation of cardiac vagal tone associated with depressed baroreflex sensitivity or affected cardiac sympathetic responsiveness in CHF patients with CI. Spontaneous cardiac baroreflex sensitivity (BRS) assessed by sequence method and spectral- and time-domain analysis of heart rate variability (HRV) were analysed in 21 chronic CHF patients. All patients performed a symptom-limited exercise test with measurement of gas exchange. Chronic incompetence which was defined as failure to achieve > or =80% of the heart rate reserve (%HRR) given by (HRpeak - HRrest)/(predictive maximal heart rate - HRrest) was observed in 14 (66%) patients. There was no significant difference in age, heart rate, peak oxygen uptake or left ventricular ejection fraction between the patients with and without CI. Although there was no significant difference in BRS, low frequency power of HRV in normalized units (LFnu) and SDNN were significantly lower in CI patients. Percentage of HRR correlated significantly with LFnu on 15 min (r=0.64, P<0.005) and, with LFnu on 24 h (r=0.52, P<0.01), SDNN (r=0.48, P=0.03) and SDANN (r=0.48, P=0.03), but not BRS (r=0.04, P=NS). Autonomic nervous system derangement is a complex process in CHF. The role of basal depressed cardiac sympathetic tone seems to contribute more closely than depressed baroreflex sensitivity to the impaired heart rate response to exercise frequently observed in CHF patients.
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PMID:Chronotropic incompetence response to exercise in congestive heart failure, relationship with the cardiac autonomic status. 1138 May 33

Congestive heart failure (CHF) is a leading cause of death. Although changes to other components contribute, it is generally agreed that much of the contractile deficit is due to reduced Ca(2+) homeostasis that includes alterations in Ca(2+) current and action potential characteristics, together with reduced Ca(2+) transient amplitude. CHF is also associated with progressive skeletal muscle dysfunction. In both cardiac and skeletal muscles, the global increase in myoplasmic Ca(2+) during depolarization, or Ca(2+) transient, appears to consist of the summation of large numbers of local, unitary Ca(2+) release events (ie, Ca(2+) sparks) resulting from the activity of a cluster of ryanodine receptors (RyRs) (ie, RyR1 or RyR2 in skeletal and cardiac muscles, respectively). RyR2 channels from failing hearts have been shown to be hyperphosphorylated by protein kinase A, leading to dissociation of FK506-binding protein 12.6 and altered RyR2 channel function. After reviewing the alterations occurring in cardiomyocytes, the present report summarizes the intrinsic alterations of Ca(2+) homeostasis in rat extensor digitorum longus skeletal muscle. They include a weaker and prolonged Ca(2+) transient that could be attributed to both a lower synchronization of the individual Ca(2+) sparks and a lower synchronization of these events triggered upon depolarization. As in cardiac muscle, these alterations in sarcoplasmic reticulum function are associated with protein kinase A-induced hyperphosphorylation of RyR1 and a concomitant reduction in FK506-binding protein 12. These specific alterations in RyR1-dependent Ca(2+) release could play a significant role in the specific force decrements in skeletal muscle as well as in the remodelling that occurs secondary to CHF.
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PMID:The role of ryanodine receptors and consequences of their alterations during cardiac insufficiency. 1964 87