Recombinant Klotho Protein Ameliorates Myocardial Ischemia/Reperfusion Injury by Attenuating Sterile Inflammation.

Currently, no effective therapy and potential target have been elucidated for preventing myocardial ischemia and reperfusion injury (I/R). We hypothesized that the administration of recombinant klotho (rKL) protein could attenuate the sterile inflammation in peri-infarct regions by inhibiting the extracellular release of high mobility group box-1 (HMGB1). This hypothesis was examined using a rat coronary artery ligation model. Rats were divided into sham, sham+ rKL, I/R, and I/R+ rKL groups (n = 5/group). Administration of rKL protein reduced infarct volume and attenuated extracellular release of HMGB1 from peri-infarct tissue after myocardial I/R injury. The administration of rKL protein inhibited the expression of pro-inflammatory cytokines in the peri-infarct regions and significantly attenuated apoptosis and production of intracellular reactive oxygen species by myocardial I/R injury. Klotho treatment significantly reduced the increase in the levels of circulating HMGB1 in blood at 4 h after myocardial ischemia. rKL regulated the levels of inflammation-related proteins. This is the first study to suggest that exogenous administration of rKL exerts myocardial protection effects after I/R injury and provides new mechanistic insights into rKL that can provide the theoretical basis for clinical application of new adjunctive modality for critical care of acute myocardial infarction.

Benefits of High-Flow Nasal Cannula Therapy for Acute Pulmonary Edema in Patients with Heart Failure in the Emergency Department: A Prospective Multi-Center Randomized Controlled Trial.

Heart failure patients with pulmonary edema presenting to the emergency department (ED) require an effective approach to deliver sufficient oxygen and reduce the rate of intubation and mechanical ventilation in the ED; conventional oxygen therapy has proven ineffective in delivering enough oxygen to the tissues. We aimed to identify whether high-flow nasal cannula (HFNC) therapy over time improved the respiratory rate (RR), lactate clearance, and certain arterial blood gas (ABG) parameters, in comparison with conventional oxygen therapy, in patients with cardiogenic pulmonary edema. This prospective, multi-institutional, and interventional study (clinical trial, reference KCT0004578) conducted between 2016 and 2019 included adult patients diagnosed with heart failure within the previous year and pulmonary edema confirmed at admission. Patients were randomly assigned to the conventional or HFNC group and treated with the goal of maintaining oxygen saturation (SpO2) ≥ 93. We obtained RR, SpO2, lactate levels, and ABG parameters at baseline and 30 and 60 min after randomization. All parameters showed greater improvement with HFNC therapy than with conventional therapy. Significant changes in ABG parameters were achieved within 30 min. HFNC therapy could therefore be considered as initial oxygen therapy. Physicians may consider advanced ventilation if there is no significant improvement in ABG parameters within 30 min of HFNC therapy.