These data indicate that although both autonomic systems play a role in AF, cholinergic stimulation is likely the main factor for spontaneous AF initiation in this animal model. Adrenergic tone modulates the initiation and maintenance of cholinergically mediated AF.

BackgroundTissue Doppler index E/è is used clinically and in multidisciplinary research for estimation of left ventricular filling pressure (LVFP) and diastolic dysfunction (DD)/heart failure with preserved ejection fraction (HFpEF). Its diagnostic accuracy is not well studied.Methods and ResultsFrom the PubMed, Scopus, Embase, and Cochrane databases, we identified 24 studies reporting E/è and invasive LVFP in preserved EF (≥50%). In random‐effects models, E/è had poor to mediocre linear correlation with LVFP. Summary sensitivity and specificity (with 95% CIs) for the American Society of Echocardiography–recommended E/è cutoffs (lateral, mean, and septal, respectively) to identify elevated LVFP was estimated by using hierarchical summary receiver operating characteristic analysis. Summary sensitivity was 30% (9–48%), 37% (13–61%), and 24% (6–46%), and summary specificity was 92% (82–100%), 91% (80–99%), and 98% (92–100%). Positive likelihood ratio (LR+) was <5 for lateral and mean E/è. LR+ was slightly >10 for septal E/è obtained from 4 studies (cumulative sample size <220). For excluding elevated LVFP, summary sensitivity for E/è (lateral, mean, and septal, respectively) was 64% (38–86%), 36% (3–74%), and 50% (14–81%), while summary specificity was 73% (54–89%), 83% (49–100%), and 89% (66–100%). Because of data set limitations, meaningful inference for identifying HFpEF by using E/è could not be drawn. With the use of quality assessment tool for diagnostic accuracy studies (Quality Assessment of Diagnostic Accuracy Studies questionnaire), we found substantial risks of bias and/or applicability.ConclusionsThere is insufficient evidence to support that E/è can reliably estimate LVFP in preserved EF. The diagnostic accuracy of E/è to identify/exclude elevated LVFP and DD/HFpEF is limited and requires further validation in a well‐designed prospective clinical trial.

Strong defibrillation shocks induce DeltaV(m) in the intramural layers of LV. During action potential plateau, intramural DeltaV(m) are typically asymmetrical (DeltaV-(m)>DeltaV+(m)) and become globally negative during very strong shocks.

Shocks applied during diastole cause direct and rapid (within 1 ms) activation of ventricular bulk over a wide range of shock strengths, supporting the excitatory hypothesis of defibrillation. Very strong shocks can cause multiphasic Vm responses and delayed activation.

Acute respiratory distress syndrome (ARDS) due to sepsis has a high mortality rate with limited treatment options. High density lipoprotein (HDL) exerts innate protective effects in systemic inflammation. However, its role in ARDS has not been well studied. Peptides such as L-4F mimic the secondary structural features and functions of apolipoprotein (apo)A-I, the major protein component of HDL. We set out to measure changes in HDL in sepsis-mediated ARDS patients, and to study the potential of L-4F to prevent sepsis-mediated ARDS in a rodent model of lipopolysaccharide (LPS)-mediated acute lung injury, and a combination of primary human leukocytes and human ARDS serum. We also analyzed serum from non-lung disease intubated patients (controls) and sepsis-mediated ARDS patients. Compared to controls, ARDS demonstrates increased serum endotoxin and IL-6 levels, and decreased HDL, apoA-I and activity of anti-oxidant HDL-associated paraoxanase-1. L-4F inhibits the activation of isolated human leukocytes and neutrophils by ARDS serum and LPS in vitro. Further, L-4F decreased endotoxin activity and preserved anti-oxidant properties of HDL both in vitro and in vivo. In a rat model of severe endotoxemia, L-4F significantly decreased mortality and reduces lung and liver injury, even when administered 1 hour post LPS. Our study suggests the protective role of the apoA-I mimetic peptide L-4F in ARDS and gram-negative endotoxemia and warrant further clinical evaluation. The main protective mechanisms of L-4F are due to direct inhibition of endotoxin activity and preservation of HDL anti-oxidant activity.