Rodent Model of Cardiopulmonary Bypass Demonstrates Systemic Inflammation and Neuromarker Changes.

Introduction: The physiologic derangements imposed by cardiopulmonary bypass (CPB) can result in complications such as postoperative delirium. We aim to validate a rodent survival model of CPB demonstrating a systemic inflammatory response and hypothesize that this contributes to post-CPB delirium.

Methods: Adult Sprague-Dawley rats were randomized to three groups: 1) Sham peripheral surgical cannulation, 2) CPB followed by acute phase harvest, or 3) CPB followed by 24-h survival.

Adenosine 2A Receptor Agonism Improves Survival in Extracorporeal Cardiopulmonary Resuscitation.

Introduction: Despite resuscitation advances including extracorporeal cardiopulmonary resuscitation (ECPR), freedom from neurologic and myocardial insult after cardiac arrest remains unlikely. We hypothesized that adenosine 2A receptor (A2AR) agonism, which attenuates reperfusion injury, would improve outcomes in a porcine model of ECPR.

Methods: Adult swine underwent 20 min of circulatory arrest followed by defibrillation and 6 h of ECPR.

Transient receptor potential vanilloid 4 channel inhibition attenuates lung ischemia-reperfusion injury in a porcine lung transplant model.

Objective: Transient receptor potential vanilloid 4 (TRPV4) is a nonselective cation channel important in many physiological and pathophysiological processes, including pulmonary disease. Using a murine model, we previously demonstrated that TRPV4 mediates lung ischemia-reperfusion injury, the major cause of primary graft dysfunction after transplant. The current study tests the hypothesis that treatment with a TRPV4 inhibitor will attenuate lung ischemia-reperfusion injury in a clinically relevant porcine lung transplant model.

The endothelium: gatekeeper to lung ischemia-reperfusion injury.

The success of lung transplantation is limited by the high rate of primary graft dysfunction due to ischemia-reperfusion injury (IRI). Lung IRI is characterized by a robust inflammatory response, lung dysfunction, endothelial barrier disruption, oxidative stress, vascular permeability, edema, and neutrophil infiltration. These events are dependent on the health of the endothelium, which is a primary target of IRI that results in pulmonary endothelial barrier dysfunction.

Purinergic P2Y2 receptor-induced activation of endothelial TRPV4 channels mediates lung ischemia-reperfusion injury.

Lung ischemia-reperfusion injury (IRI), characterized by inflammation, vascular permeability, and lung edema, is the major cause of primary graft dysfunction after lung transplantation. Here, we investigated the cellular mechanisms underlying lung IR-induced activation of endothelial TRPV4 channels, which play a central role in lung edema and dysfunction after IR. In a left lung hilar-ligation model of IRI in mice, we found that lung IRI increased the efflux of ATP through pannexin 1 (Panx1) channels at the endothelial cell (EC) membrane.