Antithrombotic drug removal from whole blood using Haemoadsorption with a porous polymer bead sorbent

Aim To evaluate the ability of the DrugSorb™-AntiThrombotic Removal (ATR) haemoadsorption device utilizing porous polymer bead sorbent technology to remove three commonly used antithrombotic drugs from whole blood. Methods and results We evaluated the removal of apixaban, rivaroxaban, and ticagrelor by the DrugSorb-ATR haemoadsorption device in a benchtop clinical scale model using bovine whole blood. Blood spiked at clinically relevant concentrations of an antithrombotic agent was continuously circulated through a 300-mL DrugSorb-ATR haemoadsorption device at a flow rate of 300 mL/min. Drug concentration was monitored over 6 h to evaluate drug removal. Results were compared with a control circuit without the haemoadsorption device. Removal rates at 30, 60, 120, and 360 minutes were: apixaban: 81.5%, 96.3%, 99.3% >99.8%; rivaroxaban: 80.7%, 95.1%, 98.9%, >99.5%; ticagrelor: 62.5%; 75%, 86.6%, >95% (all P <0.0001 vs. control). Blood pH and haematological parameters were not significantly affected by the DrugSorb-ATR haemoadsorption device when compared with the control circuit. Conclusion DrugSorb-ATR efficiently removes apixaban, rivaroxaban, and ticagrelor in a clinical-scale benchtop recirculation circuit with the bulk of removal occurring in the first 60 minutes. The clinical implications of these findings are currently investigated in patients undergoing on-pump cardiothoracic surgery in two US pivotal trials (ClinicalTrials.gov Identifiers: NCT04976530 and NCT05093504)

The urgent need for integrated science to fight COVID-19 pandemic and beyond

The COVID-19 pandemic has become the leading societal concern. The pandemic has shown that the public health concern is not only a medical problem, but also afects society as a whole; so, it has also become the leading scientifc concern. We discuss in this treatise the importance of bringing the world’s scientists together to fnd efective solu‑ tions for controlling the pandemic. By applying novel research frameworks, interdisciplinary collaboration promises to manage the pandemic’s consequences and prevent recurrences of similar pandemics

Vascular changes after cardiopulmonary bypass and ischemic cardiac arrest: roles of nitric oxide synthase and cyclooxygenase

Cardiac surgery involving ischemic arrest and extracorporeal circulation is often associated with alterations in vascular reactivity and permeability due to changes in the expression and activity of isoforms of nitric oxide synthase and cyclooxygenase. These inflammatory changes may manifest as systemic hypotension, coronary spasm or contraction, myocardial failure, and dysfunction of the lungs, gut, brain and other organs. In addition, endothelial dysfunction may increase the occurrence of late cardiac events such as graft thrombosis and myocardial infarction. These vascular changes may lead to increased mortality and morbidity and markedly lengthen the time of hospitalization and cost of cardiac surgery. Developing a better understanding of the vascular changes operating through nitric oxide synthase and cyclooxygenase may improve the care and help decrease the cost of cardiovascular operations

Impact of aging on the angiogenic potential of the myocardium: Implications for angiogenic therapies with emphasis on sirtuin agonists

The mechanisms for decreased tolerance to ischemia in the aging hearts have not been fully explored but they appear to be multifactorial. The elderly patients most often meet classification of "no-option" patients who suffer from symptoms of chronic recurrent myocardial ischemia without good options for intervention. As such these patients are in greatest need of alternative therapies for revascularization such as angiogenesis. Not only does aging and their co-morbid conditions such as hypercholesterolemia and diabetes impair the endogenous angiogenesis response but there may be decreased responsiveness to exogenous angiogenic therapies. Enhancing the effectiveness of angiogenic therapy in this ever increasing subgroup of cardiovascular patients is as yet unmet. One such promising avenue involves sirtuins. Herein, we review the effect of aging on the processes of angiogenesis and explore the implications for successful clinical treatment of myocardial ischemia with angiogenesis therapy, with particular focus on modification of sirtuins and their targets by resveratrol along with some recent patents

Healthcare resource utilization in patients receiving idarucizumab for reversal of dabigatran anticoagulation due to major bleeding, urgent surgery, or procedural interventions: interim results from the RE-VERSE AD (TM) study

Thrombosis and Hemostasi

Autologous cardiomyotissue implantation promotes myocardial regeneration, decreases infarct size, and improves left ventricular function

Background-: Cell therapy for myocardial infarction (MI) may be limited by poor cell survival and lack of transdifferentiation. We report a novel technique of implanting whole autologous myocardial tissue from preserved myocardial regions into infarcted regions. Methods and results-: Fourteen rats were used to optimize cardiomyotissue size with peritoneal wall implantation (300 μm identified as optimal size). Thirty-nine pigs were used to investigate cardiomyotissue implantation in MI induced by left anterior descending balloon occlusion (10 animals died; male-to-female transplantation for tracking with in situ hybridization for Y chromosome, n≤4 [2 donors and 2 MI animals]; acute MI implantation cohort at 1 hour, n≤13; and healed MI implantation at 2 weeks, n≤12). Assessment included echocardiography, magnetic resonance imaging, hemodynamics, triphenyltetrazolium chloride staining, and histological and molecular analyses. Tracking studies demonstrated viable implants with donor cells interspersed in the adjacent myocardium with gap junctions and desmosomes. In the acute MI cohort, treated animals compared with controls had improved perfusion by magnetic resonance imaging (1.2±0.01 versus 0.86±0.05; P<0.01), decreased MI size (magnetic resonance imaging: left ventricle, 2.2±0.5% versus 5.4±1.5%, P≤0.04; triphenyltetrazolium chloride: anterior wall, 10.3±4.6% versus 28.9±5.8%, P<0.03), and improved contractility (dP/dt, 1235±215 versus 817±817; P<0.05). In the healed MI cohort, treated animals had less decline in ejection fraction between 2 and 4 week assessment (-3±4% versus -13±-4%; P<0.05), less decline in ±dP/dt, and smaller MI (triphenyltetrazolium chloride, 21±11% versus 3±8%; P≤0.006) than control animals. Infarcts in the treated animals contained more mdr-1 cells and fewer c-kit cells with a trend for decreased expression of matrix metalloproteinase-2 and increased expression of tissue inhibitor of metalloproteinase-2. Conclusion-: Autologous cardiomyotissue implanted in an MI area remains viable, exhibits electromechanical coupling, decreases infarct size, and improves left ventricular function. Copyright © 2011 American Heart Association

Idarucizumab for Dabigatran Reversal

Thrombosis and Hemostasi