Parsimonious Effect of Pentoxifylline on Angiogenesis: A Novel Pentoxifylline-Biased Adenosine G Protein-Coupled Receptor Signaling Platform.

Angiogenesis is the physiological process of developing new blood vessels to facilitate the delivery of oxygen and nutrients to meet the functional demands of growing tissues. It also plays a vital role in the development of neoplastic disorders. Pentoxifylline (PTX) is a vasoactive synthetic methyl xanthine derivative used for decades to manage chronic occlusive vascular disorders. Recently, it has been proposed that PTX might have an inhibitory effect on the angiogenesis process. Here, we reviewed the modulatory effects of PTX on angiogenesis and its potential benefits in the clinical setting. Twenty-two studies met the inclusion and exclusion criteria. While sixteen studies demonstrated that pentoxifylline had an antiangiogenic effect, four suggested it had a proangiogenic effect, and two other studies showed it did not affect angiogenesis. All studies were either in vivo animal studies or in vitro animal and human cell models. Our findings suggest that pentoxifylline may affect the angiogenic process in experimental models. However, there is insufficient evidence to establish its role as an anti-angiogenesis agent in the clinical setting. These gaps in our knowledge regarding how pentoxifylline is implicated in host-biased metabolically taxing angiogenic switch may be via its adenosine A2BAR G protein-coupled receptor (GPCR) mechanism. GPCR receptors reinforce the importance of research to understand the mechanistic action of these drugs on the body as promising metabolic candidates. The specific mechanisms and details of the effects of pentoxifylline on host metabolism and energy homeostasis remain to be elucidated.

Hemadsorption for removal of ticagrelor and direct oral anticoagulants in cardiac surgery.

INTRODUCTION: Cardiac patients on antiplatelets or oral anticoagulation undergoing emergent cardiac surgery without appropriate washout periods are at increased risk for developing perioperative bleeding. CytoSorb is a commercially available hemadsorption adsorber that can simultaneously remove a wide range of substances including ticagrelor, and direct oral anticoagulants (DOACs). AREAS COVERED: Although CytoSorb has been used to remove various protein-bound substances, this review will specifically evaluate and review current evidence for applying CytoSorb in removing ticagrelor and DOACs using four in vitro studies, three case reports, one retrospective study and two cost analysis studies. Based on limited evidence, CytoSorb may be effective in reducing perioperative bleeding by reducing chest tube output, blood product transfusions, and re-thoracotomy rates. CytoSorb can also reduce length of intensive care unit (ICU) and hospital stay. Although, CytoSorb has an initial upfront cost, it was proven to be cost-effective due to potential health resource savings on both short- and long-term projections. EXPERT COMMENTARY: CytoSorb provides a novel strategy to remove ticagrelor and DOACs in patients requiring emergency cardiac surgery. Although promising results, more solid evidence is required to establish its clinical effectiveness in reducing perioperative bleeding, bleeding-related complications, mortality, and finally, its overall safety.