
The Effect of Caffeine on Ischemic Preconditioning
CaffeineIschemic Preconditioning1 moreIschaemic preconditioning (IP) describes the phenomenon that brief periods of ischaemia render the (myocardial) muscle more resistant to a subsequent more prolonged period of ischaemia and reperfusion. Animal studies have provided evidence that adenosine receptor stimulation is an important mediator of IP. As caffeine is an effective adenosine receptor antagonist already at concentrations reached after regular coffee consumption, we aimed to assess whether caffeine impairs IP in humans in vivo. We used a novel and well-validated model to study IP in humans: 99m-Tc-annexin A5 scintigraphy in forearm skeletal muscle. 24 healthy volunteers were randomly assigned to either caffeine (4 mg/kg/iv in 10 minutes) or saline before a protocol for IP.

Adapting Tools to Implement Stroke Risk Management to Veterans
Ischemic StrokeTransient Ischemic AttackThe purpose of this study is to develop and evaluate the local adaptation of existing stroke prevention tools into practice. A stroke prevention program is a collection of materials including written materials like pamphlets and brochures, videotapes and training guides for stroke survivors and evidence based guidelines for the doctors that provide care for them. Other tools that may be used in a stroke prevention program include devices that help patients monitor medical symptoms at home like home blood pressure machines or blood sugar monitors and messaging devices that allow reporting symptoms from home to a health care provider. We hypothesized Veterans with stroke who receive the Veteran Stroke Prevention Program would engage in better medication compliance and stroke specific quality of life compared to those who did not receive the program.

PeRiOperaTivE CardioproTection With Ivabradine in Non-cardiac Surgery
Myocardial InjuryMyocardial IschemiaPerioperative myocardial injury (PMI) after non-cardiac surgery (NCS), i.e. the elevation of postoperative troponin, occurs in nearly 20% of patients older than 45 years undergoing NCS and is independently and strongly associated with post-operative mortality (30-day mortality up to 10%). With over 300 million surgical interventions every year worldwide, PMI has a high clinical relevance on the health of the population. Heart rate (HR) is an independent and modifiable risk factor for PMI and death after non-cardiac surgery. Numerous studies showed that beta-blockers decrease myocardial ischemia after surgery in a heart-rate dependent manner, but this beneficial effect is surpassed by an increased incidence of perioperative hypotension and death. Currently, no single intervention is available to decrease the risk of perioperative cardiac complications. Ivabradine (IVA) is a negative chronotropic agent without significant effects on contractility or vascular tone and has been shown to improve outcomes in the setting of chronic and acute heart diseases. Rationale for pilot feasibility trial: the planned definitive large trial is a multicenter trial to investigate the efficacy of ivabradine to decrease perioperative myocardial injury. The intervention planned is complex and demands important resources. The investigators designed this pilot study to inform on the feasibility of the definitive large trial. This pilot study will also provide additional information that could help investigators improve the definitive large trial regarding recruitment, refinements to the study protocol and improving the participant's experience.

Effect of Permanent Right Internal Mammary Artery Occlusion on Extracardiac Coronary Collateral...
CirculationCollateral3 moreCoronary artery disease and the benefit of bypasses: Despite considerable advances in medicine, cardiovascular diseases remain the number one cause of death globally, primarily consequence of myocardial infarction (MI). Coronary collaterals exert a protective effect by providing an alternative source of blood flow to a myocardial territory potentially affected by an acute coronary occlusion. Coronary collaterals represent pre-existing inter-arterial anastomoses and as such are the natural counter-part of surgically created bypasses. Sufficient coronary collaterals have been shown to confer a significant benefit in terms of overall mortality and cardiovascular events. In this regard, the concept of augmenting coronary collateral function as an alternative treatment strategy to alter the course of CAD, as well as to control symptoms, is attractive. Durable promotion of coronary collateral circulation: Before the advent of coronary artery bypass grafting, permanent augmentation of coronary collateral supply by a single structural modification has already been attempted. Bilateral ligation of the internal mammary arteries (IMA) was performed in CAD patients to alleviate angina pectoris and electrocardiographic (ECG) signs of ischemia. The prevalent in vivo function of natural internal mammary arteries (IMA)-to-coronary artery bypasses and their anti-ischemic effect has been recently demonstrated by the investigators' research group. Levels of collateral function and myocardial ischemia were determined in a prospective, open-label clinical trial of permanent IMA device occlusion. In this study, coronary collateral function, has been shown to be augmented in the presence vs the absence of distal permanent ipsilateral IMA occlusion. These findings have been corroborated by the observed reduction in ischemia in the intracoronary ECG. After this first step, the concept of permanent right IMA occlusion will be now investigated with a randomized, sham-controlled clinical trial.

Early Feasibility Study of the SENSE Device
Hemorrhagic StrokeIschemic StrokeA single site, study of the SENSE device in up to 20 study subjects, (five healthy controls and five each with ICH, AIS with LVO and AIS without LVO) in whom SENSE can be applied within 24 hours of stroke symptom onset.

Role of Sympathetic Activation in Ischemia Reperfusion Injury
Central Sympathetic Nervous System DiseasesThis study is designed to assess the effect of forearm ischemia-reperfusion injury on sympathetic nerve activity. To determine whether reduced sympathetic responsiveness is a contributor to the protective effects of remote ischemic preconditioning. In addition it will assess whether pharmacologic inhibition of the sympathetic nervous system can ameliorate ischemia reperfusion injury induced endothelial dysfunction.

Post Occlusive Reactive Hyperemia on Gingiva Assessed by Laser Speckle Contrast Imaging
IschemiaApply the LASCA for follow-up the postocclusive microcirculation after strangulation of the gingiva in order to characterize the kinetics of the blood flow changes in human subjects.

Exercise-induced Changes in Cardiac Function & Morphology
Myocardial IschemiaExercise3 moreUntil now it has been assumed that regular endurance training has a positive influence on cardiac function and that the positive effect increases with increasing intensity. However, little is known about the effects of intense endurance stress on the heart. According to current knowledge repeated exposure to strenuous endurance activity may lead to minor but possibly irreversible damage to the heart with resultant scarring of the heart's muscle. Within this study we attempt to find out by different analytical methods - in particular magnetic resonance imaging (MRI) and ultrasound of the heart - to what extent the heart muscle is affected by an intense endurance exercise, i.e. the "Jungfrau-Marathon", and which changes can possibly be found. Due to repeated measurements we will obtain further information on the short-term course of possible changes. Hypotheses: A single bout of prolonged strenuous exercise (PSE) leads to transient alteration in cardiac function accompanied by the appearance of biomarkers for myocardial damage.

Cutaneous Remote Ischemic Preconditioning in Plastic Surgery
Ischemic PreconditioningBackground: In plastic and reconstructive surgery, free flaps are routinely used for treatment of soft tissue defects. Treatment strategies aim at reducing or preventing flap necrosis by conditioning tissue tolerance against ischemia. Although previous studies indicate that remote ischemic preconditioning (RIPC) is a systemic phenomenon, only a few studies have focused on the elucidation of its mechanisms of action. Therefore, the aim of this study is to evaluate the microcirculatory effects of remote ischemic preconditioning on a potential free flap location in a human in-vivo setting for the first time. Conclusion: Remote ischemic preconditioning improves cutaneous tissue oxygen saturation, arterial capillary blood flow and postcapillary venous flow in a remote free flap donor location. To what extent remote preconditioning might ameliorate the reperfusion injury of free flap transplantation, further clinical trials have to evaluate both in the means of microcirculatory assessment and partial or total flap loss as end points of these studies.

Clinical and Genomic Responses to Open Heart Surgery
Ischemia-reperfusion (IR) InjuryThis study will be the first large scale randomized study of remote ischemic preconditioning (RIPC) ever performed and will define the role of this novel therapy as a clinical tool. This study will also be the first to define preoperative gene expression profiles associated with poor postoperative outcomes in a control (SHAM) population of children undergoing cardiac surgery. Finally, the role of RIPC in modifying these gene expression profiles will be examined. Therefore, mechanistic insight into the proven ability of RIPC to improve markers of tissue injury, and the expected improvement in clinically relevant endpoints, will be examined.