
Pediatric Remote Ischemic Pre-conditioning Prior to Complex Cardiac Surgery
Congenital Heart DiseaseIschemia-reperfusion InjuryIn 2012, infants having surgery for congenital heart disease have a high survival. The investigators are now focused on improving how sick these infants become after surgery (short term outcomes) and their later neurodevelopment (long term outcomes). During heart surgery, cardiopulmonary bypass (CPB; the heart-lung machine) takes over heart function while the surgeon repairs the heart disease. During this surgery there are periods of time when the amount of blood going to the heart and brain is lower than usual, called "ischemia". Once the surgery is finished the blood going to the heart and brain is increased to normal again, called "reperfusion". This ischemia-reperfusion can cause injury to the heart, brain, and other organs, affecting the short and long term outcomes in these infants. Adult studies have shown that a short time of ischemia to the legs for 5-10 minutes [the legs are not damaged by a short time of ischemia, unlike the heart or brain], before severe ischemia to another distant vulnerable vital organ [like the heart or brain], can protect this other vital organ from ischemia-reperfusion injury. This is called "remote ischemic preconditioning" (RIPC). Our objective is to test whether RIPC before heart surgery can improve the recovery of the heart and brain after heart surgery in newborn babies with congenital heart disease. The investigators will test whether RIPC will result in lower peak lactate and troponin levels on the day after heart surgery. Lactate levels are a marker for how much the different tissues of the body suffer from ischemia-reperfusion injury. Troponin is released from damaged heart during ischemia-reperfusion. In our trial infants will be randomized to RIPC or control. This means each baby has an equal chance of being in one group or the other. The intervention group will have RIPC before surgery; the "control group" will not. The investigators hope this trial will lead to a larger study to test if RIPC results in fewer days on a breathing machine after surgery, lower mortality, and higher scores on neurodevelopmental tests at 2 years of age.

Induction of HO-1; a Therapeutic Approach to Reduce Ischaemia Reperfusion Injury (IRI) Following...
Graft FailureIschemia-reperfusion InjuryThis is a blinded, placebo-controlled, randomised controlled trial looking at the effects of Heme arginate (HA) on cadaveric renal transplantation. The investigators know that HA can upregulate HO-1, which has been shown to have a protective effect on animal transplants. The investigators will be giving HA/placebo to participants prior to transplant and repeat again on day 2 post-transplant and compare outcomes.

The Supplementary Role of Non-invasive Imaging to Routine Clinical Practice in Suspected Non-ST-elevation...
Chest PainMyocardial Infarction3 moreApproximately half of patients with acute chest pain, a very common reason for emergency department visits worldwide, have a cardiac cause. Two-thirds of patients with a cardiac cause are eventually diagnosed with a so-called non-ST-elevation myocardial infarction. The diagnosis of non-ST-elevation myocardial infarction is based on a combination of symptoms, electrocardiographic changes, and increased serum cardiac specific biomarkers (high-sensitive troponin T). Although being very sensitive of myocardial injury, increased high-sensitive troponin T levels are not specific for myocardial infarction. Invasive coronary angiography is still the reference standard for coronary imaging in suspected non-ST-elevation myocardial infarction. This study investigates whether non-invasive imaging early in the diagnostic process (computed tomography angiography (CTA) or cardiovascular magnetic resonance imaging (CMR)) can prevent unnecessary invasive coronary angiography. For this, patients will be randomly assigned to either one of three strategies: 1) routine clinical care and computed tomography angiography early in the diagnostic process, 2) routine clinical care and cardiovascular magnetic resonance imaging early in the diagnostic process, or 3) routine clinical care without non-invasive imaging early in the diagnostic process.

Stress Echo Ultrasound Contrast in an Urban Safety Net Hospital to Refine Ischemia Evaluation
Chest PainSymptomatic Ischemic EquivalentThe current study is designed to have broad generalizability and inform a potential shift toward greater utilization of stress echocardiography with UCA. This will be accomplished by comparing UCA stress echocardiography with myocardial SPECT among hospitalized patients presenting with atraumatic chest pain. This study seeks to demonstrate: clinical comparability of the 2 modalities (based on non-diagnostic test rates), improved care efficiency (based on length of stay), lower costs, improved provider satisfaction, and a presumed improved safety profile through the elimination of radiation exposure. Primary Hypothesis: A strategy of routine UCA (Optison™) enhanced stress echocardiography will result in a clinically non-diagnostic test rate comparable to myocardial SPECT among patients hospitalized (inpatient or hospital observation status) with atraumatic chest pain.

Switch to Ticagrelor in Critical Limb Ischemia Anti-platelet Study
Critical Limb IschemiaCritical Limb Ischemia (CLI) is defined as limb pain that occurs at rest, or impending limb loss that is caused by severe compromise of blood flow to the affected extremity. CLI is a major cause of death and disability (secondary to myocardial infarction, stroke and amputation). The mortality in patients with CLI approaches 13-25% and 50% at one and five years respectively. High on-treatment platelet reactivity (HPR) in patients treated with aspirin and clopidogrel is associated with increased risk of recurrent cardiovascular events after percutaneous coronary interventions and coronary syndromes. Preliminary studies suggest that the prevalence of HPR in patients with critical limb ischemia treated with aspirin and clopidogrel is as high a 78.5%. In patients with coronary artery disease ticagrelor overcomes non-responsiveness to clopidogrel. However, the antiplatelet effect of ticagrelor in patients with critical limb ischemia is unknown.

Pilot Study of Atorvastatin for Orthopedic Surgery Patients
Hip FractureMyocardial Ischemia1 moreUp to 35% of hip fracture patients have been shown to experience heart injury after surgery, and as many as 10% have a heart attack or die in the three months after surgery. Hip and knee arthroplasty patients are also at risk of cardiovascular complications. Patients who have these complications have higher levels of inflammation postoperatively. Statins (such as atorvastatin/Lipitor) lower cholesterol and also lessen inflammation. Both of these effects are important in preventing heart attacks. Statins have been shown to reduce the risk of heart attacks in non-surgical patients, and to protect from heart attacks in patients having heart surgery. Whether statins can prevent heart attacks in orthopedic patients is not known. In this pilot study the investigators will treat 30 orthopedic surgery patients (hip fracture, hip or knee arthroplasty) with either atorvastatin or placebo (a capsule with no study drug). Patients will start the study drug prior to surgery and take it for 45 days after surgery. Neither the doctors nor the patients will know whether they are taking atorvastatin or placebo. The investigators will look for evidence of inflammation and heart injury after surgery. The investigators hypothesize that atorvastatin will lessen the degree of postoperative inflammation found in these patients. In this study, the investigators will use a very sensitive test of heart injury that can detect problems even when patients have no symptoms. The investigators hypothesize that this test will demonstrate silent heart injury in over 50% of the hip fracture patients and over 30% of arthroplasty patients in our study. The results of this trial will help us to develop a larger study in 1000 hip fracture and joint replacement patients to determine whether atorvastatin protects orthopedic surgery patients from heart injury and other complications of surgery.

Gene Therapy for the Treatment of Chronic Stable Angina
Myocardial IschemiaThe purpose of this study is to evaluate the safety and tolerability of catheter based injections of VM202 into the heart.

Assessment of Oxygen Changes in the Heart With Cardio-vascular Magnetic Resonance Imaging
Vascular DiseasesMyocardial IschemiaThe ability of a new SSFP-based BOLD MRI sequence to assess myocardial oxygenation changes in response to coronary flow changes induced by adenosine and increased CO2-partial pressure will be examined in healthy volunteers and patients with suspected coronary artery disease. Also the susceptibility of a new SSFP-based BOLD sensitive MRI sequence to changes in arterial oxygenation will be examined. This will help understand the physiologic basis of oxygen sensitive imaging of the heart.

Reparixin in Prevention of Delayed Graft Function After Kidney Transplantation
Ischemia-Reperfusion InjuryKidney DiseasesThe chemokine CXCL8 plays a key role in the recruitment and activation of polymorphonuclear neutrophils in post-ischemia reperfusion injury after solid organ transplantation. Reparixin is a novel, specific inhibitor of CXCL8. This study is configured to explore the safety and efficacy of reparixin in preventing the delayed graft function (DGF) after kidney transplantation.

Repertaxin in Prevention of Primary Graft Dysfunction After Lung Transplantation
Ischemia-Reperfusion InjuryLung TransplantationThe chemokine CXCL8 plays a key role in the recruitment and activation of polymorphonuclear neutrophils in post-ischemia reperfusion injury after solid organ transplantation. Repertaxin is a novel, specific inhibitor of CXCL8. This study is configured to explore the safety and efficacy of repertaxin in preventing the primary graft dysfunction (PGD) after lung transplantation.