Echocardiographic Findings and Correlation with Laboratory Values in Multisystem Inflammatory Syndrome in Children (MIS-C) Associated with COVID-19.

Cardiac involvement is a common and serious problem in multisystem inflammatory syndrome in children (MIS-C). Echocardiographic evaluation of systolic and diastolic function by traditional, tissue Doppler and three-dimensional (3D) echocardiography was performed in consecutive 50 MIS-C patients during hospitalization and age-matched 40 healthy controls. On the day of worst left ventricular (LV) systolic function (echo-1), all left and right ventricular systolic function parameters were significantly lower (p < 0.001), E/A ratio was significantly lower, and averaged E/e' ratio was significantly higher (median 1.5 vs. 1.8, p < 0.05; 8.9 vs. 6.3, p < 0.001 respectively) in patients compared to control. Patients were divided into 2 groups according to 3D LV ejection fraction (LVEF) on the echo-1: Group 1; LVEF < 55%, 26 patients, and group 2; LVEF ≥ 55%, 24 patients. E/e' ratio was significantly higher in group 1 than group 2 and control at discharge (median 7.4 vs. 6.9, p = 0.005; 7.4 vs. 6.3, p < 0.001 respectively). Coronary ectasia was detected in 2 patients (z score: 2.53, 2.6 in the right coronary artery), and resolved at discharge. Compared with group 2, group 1 had significantly higher troponin-I (median 658 vs. 65 ng/L; p < 0.001), NT-pro BNP (median 14,233 vs. 1824 ng/L; p = 0.001), procalcitonin (median 10.9 vs. 2.1 µg/L; p = 0.009), ferritin (median 1234 vs. 308 µg/L; p = 0.003). The most common findings were ventricular systolic dysfunction recovering during hospitalization, and persisting LV diastolic dysfunction in the reduced LVEF group at discharge. Coronary artery involvement was rare in the acute phase of the disease. Also, in MIS-C patients, the correlation between LV systolic dysfunction and markers of inflammation and cardiac biomarkers should be considered.

Sweroside Effectively Protects Against Ischemia/Reperfusion Injury by Regulating Excitation-contraction Coupling / 中国实验方剂学杂志

ObjectiveTo explore the effect of sweroside on the protection of cardiac systolic/diastolic function during ischemia/reperfusion （I/R） injury. MethodTwenty-four healthy male SD rats were randomly divided into control group， model group， 10 μmol·L-1 sweroside group and 1 μmol·L-1 digoxin group. The I/R injury was modeled by Langendorff and ligation of the left anterior descending coronary artery. The infarct size in each group was measured by 2，3，5-triphenyltetrazolium chloride （TTC） staining and hemodynamic parameters such as left ventricular diastolic pressure （LVDP）， left ventricular end-diastolic pressure （LVEDP）， left ventricular end-systolic pressure （LVESP）， maximum rate of rising of left ventricular pressure （+dp/dtmax） and maximum rate of decreasing of left ventricular pressure （-dp/dtmax） of rat isolated heart were detected by Powerlab. In addition， neonatal rat cardiomyocytes （NRCMs） were isolated and randomly divided into control group， model group， 1 μmol·L-1 sweroside group and 10 μmol·L-1 sweroside group. Hypoxia/reoxygenation （H/R） injury model was established. Cardiac systolic function and calcium transients were examined by multi-functional cell imaging analyzer and laser confocal microscope. Furthermore， real-time polymerase chain reaction（Real-time PCR） was used to verify the mRNA expression of excitation-contraction coupling genes such as L-type calcium channel （Cacnb2）， cytochrome c oxidase subunit 6A2 （Cox6a2）， troponin （Tnnc1， Tnni3， Tnnt2）， actin （Actc1）， and myosin （Myh6， Myl2， Myl4） according to the results of previous transcriptome sequencing and literature investigation. Differentially expressed genes were subjected to cluster analysis. ResultCompared with the conditions in the control group， increased cardiac infarction size （P<0.01） and LVEDP （P<0.01） and decreased LVDP （P<0.01） and LVESP （P<0.05） were observed in the model group， with +dp/dtmax of increasing trend while -dp/dtmax decreasing. Moreover， the cell viability， heart rate and contraction amplitude of NRCMs was reduced （P<0.01）， while the contraction duration， time to peak and relaxation time was elevated （P<0.01） in the model group. Interestingly， sweroside could reverse these indicators （P<0.05）. In addition， the expression of Cacnb2， Cox6a2， Tnnc1， Tnni3， Tnnt2， Actc1， and Myh6， Myl2， and Myl4 was down-regulated in the model group （P<0.05， P<0.01）， but sweroside could up-regulate the expression of the above genes （P<0.05）. ConclusionSweroside effectively regulated Ca2+ level in NRCMs， enhanced cardiac systolic function， and protected against H/R injury by regulating excitation-contraction coupling.

Luteolin Enhances Sarcoplasmic Reticulum Ca2+-ATPase Activity through p38 MAPK Signaling thus Improving Rat Cardiac Function after Ischemia/Reperfusion.

BACKGROUND/AIMS: A major challenge for current therapeutic strategies against ischemia/reperfusion (I/R) is the lack of effective drugs. Considering luteolin enhances the activity of sarcoplasmic reticulum Ca2+-ATPase (SERCA2a) to improve the systolic/diastolic function of rat hearts and cardiomyocytes during the I/R process, we studied the regulatory function of the p38 MAPK pathway in this protective mechanism. METHODS: Isolated cardiomyocytes and perfused hearts were separately divided into five groups and used to investigate I/R. The phosphorylation of p38 and phospholamban (p-PLB), the levels and activity of SERCA2a and the levels of proteins related to apoptosis were measured. Apoptotic cells were assessed using the TUNEL assay. Single-cell shortening, Ca2+ transients, and the decay of the mitochondrial membrane potential (Δψm) were detected. RESULTS: The p38 MAPK pathway was activated during the I/R process, and inhibiting it with SB203580 promoted p-PLB, which enhanced the activity of SERCA2a and relieved the calcium overload to promote the recovery of the Δψm and reduce cardiomyocyte apoptosis in I/R. Luteolin also suppressed the activation of the p38 MAPK pathway and showed cardioprotective effects during I/R injury. CONCLUSIONS: We conclude that luteolin enhances SERCA2a activity to improve systolic/diastolic function during I/R in rat hearts and cardiomyocytes by attenuating the inhibitive effects of the p38 pathway on p-PLB.