Identifying cellular mechanisms of zinc-induced relaxation in isolated cardiomyocytes.

We tested several molecular and cellular mechanisms of cardiomyocyte contraction-relaxation function that could account for the reduced systolic and enhanced diastolic function observed with exposure to extracellular Zn(2+). Contraction-relaxation function was monitored in isolated rat and mouse cardiomyocytes maintained at 37°C, stimulated at 2 or 6 Hz, and exposed to 32 µM Zn(2+) or vehicle. Intracellular Zn(2+) detected using FluoZin-3 rose to a concentration of ∼13 nM in 3-5 min. Peak sarcomere shortening was significantly reduced and diastolic sarcomere length was elongated after Zn(2+) exposure. Peak intracellular Ca(2+) detected by Fura-2FF was reduced after Zn(2+) exposure. However, the rate of cytosolic Ca(2+) decline reflecting sarcoplasmic reticulum (SR) Ca(2+)-ATPase (SERCA2a) activity and the rate of Na(+)/Ca(2+) exchanger activity evaluated by rapid Na(+)-induced Ca(2+) efflux were unchanged by Zn(2+) exposure. SR Ca(2+) load evaluated by rapid caffeine exposure was reduced by ∼50%, and L-type calcium channel inward current measured by whole cell patch clamp was reduced by ∼70% in cardiomyocytes exposed to Zn(2+). Furthermore, ryanodine receptor (RyR) S2808 and phospholamban (PLB) S16/T17 were markedly dephosphorylated after perfusing hearts with 50 µM Zn(2+). Maximum tension development and thin-filament Ca(2+) sensitivity in chemically skinned cardiac muscle strips were not affected by Zn(2+) exposure. These findings suggest that Zn(2+) suppresses cardiomyocyte systolic function and enhances relaxation function by lowering systolic and diastolic intracellular Ca(2+) concentrations due to a combination of competitive inhibition of Ca(2+) influx through the L-type calcium channel, reduction of SR Ca(2+) load resulting from phospholamban dephosphorylation, and lowered SR Ca(2+) leak via RyR dephosphorylation. The use of the low-Ca(2+)-affinity Fura-2FF likely prevented the detection of changes in diastolic Ca(2+) and SERCA2a function. Other strategies to detect diastolic Ca(2+) in the presence of Zn(2+) are essential for future work.

Cognitive Biases in the Era of COVID-19 : A Case of Clostridium sporogenes Bacteremia in a Patient with Small Bowel Obstruction.

Clostridium sporogenes bacteremia in immunocompetent patients is rare with very few reported cases in the literature. We present a case of Clostridium sporogenes bacteremia in an 81-year-old immunocompetent man with small bowel obstruction and hypoxemia during the COVID-19 pandemic. Routine monitoring of prognostic inflammatory markers for COVID-19 created a unique challenge in the management of our patient who developed sepsis with respiratory symptoms. Upon review, bacteremia from Clostridium sporogenes was associated with high mortality rates and could produce similar elevations in the inflammatory markers observed in COVID-19 pneumonia. Further, we reviewed the cognitive biases encountered when monitoring these inflammatory markers during the management of our patient with Clostridium sporogenes bacteremia, who was initially thought to have COVID-19 disease. While our patient ultimately tested negative for COVID-19, early administration of empiric antimicrobial therapy without source control failed to prevent clinical decompensation.