Evaluation of Real-Life Investigational Use of Enoximone in Asthma, the Third Step in Drug Repurposing: A Preliminary Report.

Background: The population of uncontrolled asthma patients represents a large therapeutic burden. The PDE3-inhibitor enoximone is a strong and quick bronchodilator and is known to successfully treat life-threatening bronchial asthma (status asthmaticus). Translational mice models showed anti-inflammatory effects when PDE3 was targeted.

PDE3-inhibitor enoximone prevented mechanical ventilation in patients with SARS-CoV-2 pneumonia.

Background: Standard care in severe SARS-CoV-2 pneumonia complicated by severe dyspnea and respiratory failure, consists of symptom reduction, ultimately supported by mechanical ventilation. Patients with severe SARS-CoV-2, a prominent feature of COVID-19, show several similar symptoms to Critical Asthma Syndrome (CAS) patients, such as pulmonary edema, mucus plugging of distal airways, decreased tissue oxygenation, (emergent) exhaustion due to severe dyspnea and respiratory failure. Prior application of elective phosphodiesterase (PDE)3-inhibitors milrinone and enoximone in patients with CAS yielded rapid symptomatic relief and reverted the need for mechanical ventilation, due to their bronchodilator and anti-inflammatory properties.

(Oral) enoximone in asthma.

https://bit.ly/33D9Dgd.

PDE3 Inhibition Reduces Epithelial Mast Cell Numbers in Allergic Airway Inflammation and Attenuates Degranulation of Basophils and Mast Cells.

Epithelial mast cells are generally present in the airways of patients with allergic asthma that are inadequately controlled. Airway mast cells (MCs) are critically involved in allergic airway inflammation and contribute directly to the main symptoms of allergic patients. Phosphodiesterase 3 (PDE3) tailors signaling of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), which are critical intracellular second messenger molecules in various signaling pathways.

A pathophysiological role of PDE3 in allergic airway inflammation.

Phosphodiesterase 3 (PDE3) and PDE4 regulate levels of cyclic AMP, which are critical in various cell types involved in allergic airway inflammation. Although PDE4 inhibition attenuates allergic airway inflammation, reported side effects preclude its application as an antiasthma drug in humans. Case reports showed that enoximone, which is a smooth muscle relaxant that inhibits PDE3, is beneficial and lifesaving in status asthmaticus and is well tolerated.

Cardiac output measured by uncalibrated arterial pressure waveform analysis by recently released software version 3.02 versus thermodilution in septic shock.

To evaluate the 3.02 software version of the FloTrac/Vigileo™ system for estimation of cardiac output by uncalibrated arterial pressure waveform analysis, in septic shock. Nineteen consecutive patients in septic shock were studied.

The impact of open versus closed format ICU admission practices on the outcome of high risk surgical patients: a cohort analysis.

Background: In the year 2000, the organizational structure of the ICU in the Zaandam Medical Centre (ZMC) changed from an open to a closed format ICU. The objective of this study was to evaluate the effect of this organizational change on outcome in high risk surgical patients.

Methods: The medical records of all consecutive high risk surgical patients admitted to the ICU from 1996 to 1998 (open format) and from 2003 to 2005 (closed format), were reviewed.

Cardiac output derived from arterial pressure waveform analysis without calibration vs. thermodilution in septic shock: evolving accuracy of software versions.

Background And Objective: We studied the evolution of software in the accuracy of the FloTrac/Vigileo system to measure cardiac output less invasively from arterial pressure waveform analysis without calibration, in comparison with pulmonary artery catheter-derived thermodilution measurements, in patients with septic shock and presumed alterations in vascular tone.

Methods: Nine patients who received a pulmonary artery catheter and were on mechanical ventilation and in sinus rhythm were monitored by the FloTrac/Vigileo. Paired cardiac output measurements by both techniques were analysed for 86 measurements in four patients using the 1.