Reperfusion Injury

This study is open to adults with ST elevation myocardial infarction (heart attack) undergoing primary percutaneous coronary intervention (PCI). The purpose of this study is to determine whether a medicine called Xolatryp is safe and effective in improving cardiac outcomes. One dose of Xolatryp will be tested in this study. Participants are put into two groups randomly, which means by chance. One group receives a single 6-hour continuous intravenous infusion of Xolatryp and one group receives placebo. Participants are in the study for about 30 days. Placebo infusion looks like Xolatryp but do not contain any medicine. Participants are followed up via telephone and there is one visit to the study site on day 30. Heart health is assessed based on the analysis of blood samples, which are collected at the study site, via electrocardiogram (ECG), echocardiogram and cardiac magnetic resonance (CMR) imaging. At the end of the study, the results are compared between the two groups. During the study, the doctors also regularly check the general health of the participants.

Approximately 15,200 children receive cardiopulmonary resuscitation (CPR) for in-hospital cardiac arrest (IHCA) each year in the United States. Of these, about 60% are less than one year of age. Most IHCA (85-90%) occurs in intensive care units (ICU) or other monitored settings. Risk of IHCA is higher among children with cardiac disease compared to children with other diagnoses. A report based on the Pediatric Cardiac Critical Care Consortium (PC4) registry found 3.1% of children hospitalized in pediatric cardiac ICUs had a cardiac arrest; rates varied from 1% to 5.5 % across sites. Survival to hospital discharge after CA in children included in the PC4 registry was 53%, and lower for medical cardiac patients (37.7%) than for surgical cardiac patients (62.5%). Among survivors of pediatric IHCA, neurologic morbidities are common including cognitive, motor, and adaptive functional deficits. Despite high mortality and morbidity, treatment for children after IHCA is mainly supportive. Preventing fever and hypotension, maintaining normoxia, and treating seizures are emphasized. Ischemia-reperfusion injury to the brain is a primary cause of neurologic morbidity after IHCA. Ischemia-reperfusion leads to increased production of cytotoxic mitochondrial reactive oxygen species (ROS). Recently, specific wavelengths of near infrared light (NIR) (750 nm and 950 nm) have been discovered to partially inhibit cytochrome c oxidase activity (COX), reversibly reducing mitochondrial respiration and generation of ROS. Light Utilization COX Inhibitory Device (LUCID) is a novel medical device intended to safely deliver therapeutic NIR to the infant brain to prevent reperfusion injury. This protocol describes the "LUCID Therapy for Infant Cardiac Arrest" (LUTICA) clinical trial. LUTICA will investigate the safety, feasibility, acceptability, and probable benefit of the LUCID device in infants with acquired or congenital cardiac disease who experience unplanned IHCA. The hypothesis of the LUTICA trial is that application of the LUCID light box and cap immediately following IHCA in infants with acquired or congenital heart disease will be safe, feasible, and acceptable in the ICU setting, and demonstrate probable benefit toward favorable neurological outcomes.

COOLHEAD-2b is a multicentre, phase 2, prospective, randomised, controlled, open-label, blinded-endpoint trial evaluating the safety and efficacy of non-invasive convective head cooling as an adjunct to endovascular thrombectomy (EVT) in patients with acute anterior circulation ischaemic stroke. Head cooling is initiated as early as possible, including during inter-hospital transfer, and continued until one hour after reperfusion. The primary efficacy endpoint is final infarct volume at 24 hours.

Acute myocardial infarction with ST segment elevation is often accompanied by a totally occluded coronary artery. Which has deleterious effects on heart muscle. Primary percutaneous coronary intervention is the most effective mode of treatment for ST-elevation myocardial infarction (STEMI) patients. Despite the restoration of the blood flow, 30-60% of patients develop microvascular obstruction, which lowers the effects of the coronary blood flow restoration. The most advanced coronary microvascular obstruction presents as a no-reflow phenomenon, which is an abrupt deceleration or absence of coronary flow following stent implantation. Several pharmacological treatments have been proposed, as well as deferred stenting, but none of them really helped. Thus, new ways of alleviating coronary obstruction are warranted. One of the new ways of mitigating the reperfusion injury is intracoronary hypothermia, which showed to be safe on a handful of patients in small series. In the animal studies, intracoronary hypothermia demonstrated a protective effect in terms of reducing infarct area. But clinical studies failed to reproduce the protective effects of intracoronary hypothermia. Thus, our study, using a modified hypothermia protocol, will test the hypothermia hypothesis.

Liver transplantation remains the only cure for patients with end-stage liver disease. Despite continuous advances in medical care, ischemia-reperfusion injury (IRI) (tissue damage that occurs when blood supply is restored to an area that has been deprived of oxygen) remains a major contributor to complications with the newly transplanted liver. IRI can lead to a condition known as post-reperfusion syndrome that involves profound narrowing of blood vessels, significantly low blood pressure, and an increased requirement of medication to control blood pressure. In some cases, post-reperfusion syndrome can progress to a condition known as post-reperfusion vasoplegia which is a condition where severely low blood pressure persists even after blood flow is restored to the liver. This is often accompanied by complications such as improperly functioning kidneys, blood clotting disorders, and complications with the transplanted liver that can significantly affect patient outcomes. Recent studies have shown than inhaled nitric oxide (a gas that can relax blood vessels) can reduce the severity of IRI in the liver. This study is being conducted to determine whether the administration of inhaled nitric oxide during surgery reduces the severity of post-reperfusion syndrome and the incidence of post-reperfusion vasoplegia in adult patients undergoing liver transplantation. This is a before-and-after study design that will involve both the retrospective collection of data between the time period of January 1, 2020 - May 31, 2025 and prospective interventions involving adult liver transplant recipients.

The purpose of this project is to test the feasibility and safety of inhaled hydrogen gas (H2) administration as a rescue therapy during cardiac arrest requiring extracorporeal cardiopulmonary resuscitation (ECPR, i.e. mechanical circulatory support). Under exemption from informed consent, patients undergoing refractory cardiac arrest in the cardiac ICU at a participating center will be randomized to standard therapy with or without the administration of 2% hydrogen in gases administered via the ventilator and ECMO membrane for 72 hours.