Intraoperative Oxygen Treatment, Oxidative Stress, and Organ Injury Following Cardiac Surgery: A Randomized Clinical Trial.

Importance: Liberal oxygen (hyperoxia) is commonly administered to patients during surgery, and oxygenation is known to impact mechanisms of perioperative organ injury.

Objective: To evaluate the effect of intraoperative hyperoxia compared to maintaining normoxia on oxidative stress, kidney injury, and other organ dysfunctions after cardiac surgery.

Design, Setting, And Participants: This was a participant- and assessor-blinded, randomized clinical trial conducted from April 2016 to October 2020 with 1 year of follow-up at a single tertiary care medical center.

Technical Considerations in Laparoscopic-Assisted Endoscopic Retrograde Cholangiography.

The use of endoscopic retrograde cholangiography (ERCP) for diagnostic and therapeutic interventions on the pancreaticobiliary system has steadily increased, but the standard approach through the oropharynx is prohibited after Roux-en-Y (RYGB) gastric bypass surgery. Laparoscopic access to the gastric remnant allows for the completion of ERCP using the standard side-viewing duodenoscope to facilitate the completion of standard and advanced endoscopic maneuvers. Here, we describe our experience with the technical aspects of safe and effective performance of laparoscopic-assisted ERCP.

Hyperoxia Increases Kidney Injury During Renal Ischemia and Reperfusion in Mice.

Background: Renal ischemia and reperfusion (IR) contribute to perioperative acute kidney injury, and oxygen is a key regulator of this process. We hypothesized that oxygen administration during surgery and renal IR would impact postoperative kidney function and injury in mice.

Methods: Mice were anesthetized, intubated, and mechanically ventilated with a fraction of inspired oxygen (F io2 ) 0.

Targeting Soluble Guanylyl Cyclase during Ischemia and Reperfusion.

Ischemia and reperfusion (IR) damage organs and contribute to many disease states. Few effective treatments exist that attenuate IR injury. The augmentation of nitric oxide (NO) signaling remains a promising therapeutic target for IR injury.

SOLUBLE GUANYLYL CYCLASE ACTIVATION RESCUES HYPEROXIA-INDUCED DYSFUNCTION OF VASCULAR RELAXATION.

Introduction: Perioperative alterations in perfusion lead to ischemia and reperfusion injury, and supplemental oxygen is administered during surgery to limit hypoxic injury but can lead to hyperoxia. We hypothesized that hyperoxia impairs endothelium-dependent and endothelium-independent vasodilation but not the vasodilatory response to heme-independent soluble guanylyl cyclase activation. Methods: We measured the effect of oxygen on vascular reactivity in mouse aortas.

Impact of Inhaled Oxygen on Reactive Oxygen Species Production and Oxidative Damage during Spontaneous Ventilation in a Murine Model of Acute Renal Ischemia and Reperfusion.

Introduction: Acute kidney injury (AKI) affects 10% of patients following major surgery and is independently associated with extra-renal organ injury, development of chronic kidney disease, and death. Perioperative renal ischemia and reperfusion (IR) contributes to AKI by, in part, increasing production of reactive oxygen species (ROS) and leading to oxidative damage. Variations in inhaled oxygen may mediate some aspects of IR injury by affecting tissue oxygenation, ROS production, and oxidative damage.

Toll-like receptor 3-mediated inflammation by p38 is enhanced by endothelial nitric oxide synthase knockdown.

Background: Vascular dysfunction is commonly seen during severe viral infections. Endothelial nitric oxide synthase (eNOS), has been postulated to play an important role in regulating vascular homeostasis as well as propagation of the inflammatory reaction. We hypothesized that the loss of eNOS would negatively impact toll-like receptor 3 (TLR3) signaling and worsen vascular function to viral challenge.

Endothelial nitric oxide synthase modulates Toll-like receptor 4-mediated IL-6 production and permeability via nitric oxide-independent signaling.

Endothelial dysfunction, characterized by changes in eNOS, is a common finding in chronic inflammatory vascular diseases. These states are associated with increased infectious complications. We hypothesized that alterations in eNOS would enhance the response to LPS-mediated TLR4 inflammation.

Upper Extremity Pulse Pressure Predicts Amputation-Free Survival after Lower Extremity Bypass.

Increased pulse pressure reflects pathologic arterial stiffening and predicts cardiovascular events and mortality. The effect of pulse pressure on outcomes in lower extremity bypass patients remains unknown. We thus investigated whether preoperative pulse pressure could predict amputation-free survival in patients undergoing lower extremity bypass for atherosclerotic occlusive disease.

Ultrasound Modulates the Splenic Neuroimmune Axis in Attenuating AKI.

We showed previously that prior exposure to a modified ultrasound regimen prevents kidney ischemia-reperfusion injury (IRI) likely via the splenic cholinergic anti-inflammatory pathway (CAP) and α7 nicotinic acetylcholine receptors (α7nAChR). However, it is unclear how ultrasound stimulates the splenic CAP. Further investigating the role of the spleen in ischemic injury, we found that prior splenectomy (-7d) or chemical sympathectomy of the spleen with 6-hydroxydopamine (6OHDA; -14d) exacerbated injury after subthreshold (24-minute ischemia) IRI.