This study was undertaken to determine the impact of sarcomere length (SL) on the level of cooperative activation of the cardiac myofilament at physiological [Mg2+]. Active force development was measured in skinned rat cardiac trabeculae as a function of free [Ca2+] at five SLs (1.85–2.25 μm; 1 mM free [Mg2+]; 15°C). Only muscle preparations with minimal force rundown during the entire protocol were included in the analysis (average 7.2 ± 1.7%). Median SL was measured by on-line computer video micrometry and controlled within 0.01 μm. Care was taken to ensure a sufficient number of data points in the steep portion of the [Ca2+]-force relationship at every SL to allow for accurate fit of the data to a modified Hill equation. Multiple linear regression analysis of the fit parameters revealed that both maximum, Ca2+-saturated force and Ca2+sensitivity were a significant function of SL ( P < 0.001), whereas the level of cooperativity did not depend on SL ( P = 0.2). Further analysis of the [Ca2+]-force relationships revealed a marked asymmetry that, also, was not affected by SL ( P = 0.2–0.6). Finally, we found that the level of cooperativity in isolated skinned myocardium was comparable to that reported for intact, nonskinned myocardium. Our results suggest that an increase in SL induces an increase in the Ca2+ responsiveness of the cardiac sarcomere without affecting the level of cooperativity.

Background Identification of risk factors of severe Covid‐19 is critical for improving therapies and understanding SARS‐CoV‐2 pathogenesis. Methods We analyzed 184 patients hospitalized for Covid‐19 in Livingston, New Jersey for clinical characteristics associated with severe disease. Results The majority of Covid‐19 patients had diabetes mellitus (DM) (62.0%), Pre‐DM (23.9%) with elevated FBG, or a BMI > 30 with normal HbA1C (4.3%). SARS‐CoV‐2 infection was associated with new and persistent hyperglycemia in 29 patients, including several with normal HbA1C levels. Forty‐four patients required intubation, which occurred significantly more often in patients with DM as compared to non‐diabetics. Conclusions Severe Covid‐19 occurs in the presence of impaired glucose metabolism in patients, including those with DM, PreDM and obesity. Covid‐19 is asociated with elevated FBG and several patients presented with new onset DM or in DKA. The association of dysregulated glucose metabolism and severe Covid‐19 suggests that SARS‐CoV‐2 pathogenesis involves a novel interplay with glucose metabolism. Exploration of pathways by which SARS‐CoV‐2 interacts glucose metabolism is critical for understanding disease pathogenesis and developing therapies. This article is protected by copyright. All rights reserved.

Background: Identification of risk factors of severe Covid-19 is critical for improving therapies and understanding SARS-CoV-2 pathogenesis. Methods: We analyzed 184 patients hospitalized for Covid-19 in Livingston, New Jersey for clinical characteristics associated with severe disease. Results: The majority of Covid-19 patients had diabetes mellitus (DM) (62.0%), Pre-DM (23.9%) with elevated FBG, or a BMI > 30 with normal HbA1C (4.3%). SARS-CoV-2 infection was associated with new and persistent hyperglycemia in 29 patients, including several with normal HbA1C levels. Forty-four patients required intubation, which occurred significantly more often in patients with DM as compared to non-diabetics. Conclusions: Severe Covid-19 occurs in the presence of impaired glucose metabolism in patients with SARS-CoV-2 infection. The association of dysregulated glucose metabolism and severe Covid-19 suggests a previously unrecognized manifestation of primary SARS-CoV-2 infection. Exploration of pathways by which SARS-CoV-2 impacts glucose metabolism is critical for understanding disease pathogenesis and developing therapies.

ObjectivesThe purpose of this work was to describe the entity and mechanism of adenosine-insensitive focal atrial tachycardia (AT).