Ca2þ signaling in striated muscle cells is critically dependent upon thin filament proteins tropomyosin (Tm) and troponin (Tn) to regulate mechanical output. Using in vitro measurements of contractility, we demonstrate that even in the absence of actin and Tm, human cardiac Tn (cTn) enhances heavy meromyosin MgATPase activity by up to 2.5-fold in solution. In addition, cTn without Tm significantly increases, or superactivates sliding speed of filamentous actin (F-actin) in skeletal motility assays by at least 12%, depending upon [cTn]. cTn alone enhances skeletal heavy meromyosin's MgATPase in a concentration-dependent manner and with submicromolar affinity. cTn-mediated increases in myosin ATPase may be the cause of superactivation of maximum Ca 2þ -activated regulated thin filament sliding speed in motility assays relative to unregulated skeletal F-actin. To specifically relate this classical superactivation to cardiac muscle, we demonstrate the same response using motility assays where only cardiac proteins were used, where regulated cardiac thin filament sliding speeds with cardiac myosin are >50% faster than unregulated cardiac F-actin. We additionally demonstrate that the COOHterminal mobile domain of cTnI is not required for this interaction or functional enhancement of myosin activity. Our results provide strong evidence that the interaction between cTn and myosin is responsible for enhancement of cross-bridge kinetics when myosin binds in the vicinity of Tn on thin filaments. These data imply a novel and functionally significant molecular interaction that may provide new insights into Ca 2þ activation in cardiac muscle cells.

A commentary on this article appears in this issue on page 1321.

Introduction: The importance of obstructive sleep apnea in patients undergoing surgery with general anesthesia is well-defined, but the surgical and anesthetic implications of other sleep disorders are less clear. We sought to evaluate response to surgery with general anesthesia in patients with central disorders of hypersomnolence or restless legs syndrome.Methods: We surveyed patients on their most recent surgical procedure with general anesthesia, querying about procedure, recovery, and any changes in sleep disorder symptomatology following the procedure.Results: Forty-five patients with restless legs syndrome and 57 patients with central disorders of hypersomnolence (15 narcolepsy type 2, 1 narcolepsy type 1, 30 idiopathic hypersomnia, 1 Kleine-Levin syndrome, and 10 subjective sleepiness) completed the survey, with response rates of 45.5 and 53.8%, respectively. While patients in both groups were equally likely to report surgical complications and difficulty awakening from anesthesia, hypersomnolent patients were more likely to report worsened sleepiness (40% of the hypersomnolent group vs. 11% of the RLS group, p = 0.001) and worsening of their sleep disorder symptoms (40% of the hypersomnolent group vs. 9% of the RLS group, p = 0.0001).Conclusion: Patients with sleep disorders other than sleep apnea frequently report surgical or anesthetic complications. Patients with hypersomnolence disorders commonly perceive that their sleep disorder worsened following a procedure; whether this might be related to long term effects of general anesthesia in a particularly vulnerable clinical population requires further study.

We report on the use of systemic heparinization following thrombolysis with intravenous tissue plasminogen activator (t-PA) for acute ischemic large vessel stroke, in the setting of COVID-19-induced hypercoagulability, with partial recanalization of the internal carotid artery. Off-label systemic heparinization was used within 12 hours of t-PA administration, after extensive multidisciplinary collaboration and family discussion, given evidence of severe hypercoagulability. We conclude that thrombolysis should be considered for all eligible patients with suspected or confirmed COVID-19 and acute ischemic stroke, and systemic anticoagulation, although with inherent risks, may be a useful adjunct treatment modality in selected patients who have received intravenous thrombolysis.