Prof. B. Preckel MA MD PhD

Helium induces profound protection against ischemia-reperfusion in animals and humans. However, only sparse data are available regarding a possible molecular mechanism of this protection. 
Caveolins, structural scaffolding proteins, allow for organization of signalling molecules in caveolae, membrane invaginations enriched in lipids. Caveolin-3 (Cav-3) is a heart specific isoform that is modulated by volatile anesthetics and is required for cardiac protection. As Caveolins are closely related to the cytoskeleton we aim to investigate the role of these proteins, there binding partners and the cytoskeleton in Helium induced organ protection. (Project led by Dr. N.C. Hauck-Weber)

1. B. Organ protection by helium in human tissue

The capacity to induce preconditioning with helium could be useful for patients subjected to inevitable organ ischemia; e.g. during vascular surgery, organ transplantation, cardiac surgery. Helium organ protection is investigated in clinical settings as well as in studies several studies in volunteers, to translate the findings from the laboratory to the clinical setting.
HUVEC (Human Umbilical Vein Endothelial Cells) are frequently used as an in vitro model for investigations on endothelial cell damage. Vascular endothelial cells form the inner lining of all blood vessels. Programmed cell death of these cells, called apoptosis, plays a major role in the development and progression of common cardiovascular diseases like atherosclerosis and is also involved in tissue damage after myocardial ischemia. We investigate whether preconditioning with helium reduces apoptosis in HUVEC by measuring expression of adhesion molecules and different apoptotic markers in both adherent cells and in microparticles in collaboration with the laboratory of experimental clinical chemistry (LEKC) of the AMC.
Gas embolism, defined as the entry of gas into vascular structures, can occur in many clinical environments as an iatrogenic complication and in diving medicine. In most cases gas embolism is in fact an air embolism, although the medical use of other gases (such as carbon dioxide) can also result in this condition. Air bubbles may reach any organ, but their effect on the cerebral and cardiac circulation is particularly deleterious because these organs are highly vulnerable for hypoxia. Hyperbaric oxygen therapy has been advocated as a therapy for gas embolism, whereby the patient breathes 100% oxygen at a pressure above that of the atmosphere at sea level. Helium might be an alternative to treat or even prevent development of gas embolism. In close cooperation with the Diving Medical Center, Royal Netherlands Navy, we investigate the effects of helium in animal models of cerebral air embolism.

1. C. Remote Ischaemic Pre-Conditioning

Remote ischaemic preconditioning (RIPC) by repeated short periods of limb ischaemia using a tourniquet protects against ischaemia/reperfusion damage after surgery. The serum taken from volunteers and also animals therefore might contain several potentially protective factors, which are investigated in an in vitro model of HUVEC and other cells. Here we also are interested in a possible role for Caveolin. (Co-operation with the University of Kiel, Priv.-Doz. Dr. Martin Albrecht, Professor Dr. Berthold Bein, Project led by Dr. N.C. Hauck-Weber). In clinical studies, we investigate the outcome and molecular basis for Remote Conditioning in humans

Patient safety and improvement of quality of perioperative care, including anesthetic care for the diabetic patient, connects to the AMC Amsterdam Public Health Research Institute research objectives. Within this area, simulation research, decision support and safety of sedation practices, as well as postoperative detection of possible complications and remote wireless monitoring are parts of the activities to improve patient care on the OR but also on the ward.

2. Optimizing perioperative metabolism as a cardiovascular risk factor
The incidence of diabetes mellitus in the general population is increasing into epidemic proportions and this is reflected in the surgical population. Patients with diabetes mellitus are at risk of postoperative complications; however the evidence for treatment of perioperative diabetes is surprisingly scarce. In this clinical research line we aim to identify risk factors for postoperative complications in patients with diabetes, improve detection of hyperglycaemia with novel monitoring techniques and study perioperative treatment in randomized clinical trials. Another focus is perioperative hyperglycaemia without a pre-existing diagnosis of diabetes mellitus and the diagnosis and impact of diabetes mellitus on perioperative cerebral and cardiac autonomic failure. Investigating the effects of novel anti-diabetics in the perioperative period – like effects of GLP1 inhibitors – will help to understand whether insulin injections (with high risk for subsequent detrimental hypoglycemia) can be minimized in the perioperative period. 
Another important aspect of our research is the protection of the diseased animal by conditioning, e.g. in experimental models of diabetes and hypertension we have investigated the effectiveness of helium induced cardioprotection.


3. Perioperative patient safety

A Patient-Safety Board of Anesthesiology has been instituted to implement tools for improving safety issues during the perioperative process, e.g. effects of Emergency Cards and Cognitive Aids in the OR as well as on the ward, the possibility of nation wide constant drug labeling in anesthesia departments, adequacy of analgesia during surgery, and quality and use of standard operating procedures. 
Fluid management and goal directed therapy in patients subjected to major non-cardiac surgery as well as microcirculation during transthoracic oesophageal cardia resections is studied using sophisticated non-invasive hemodynamic monitoring. In cardiac surgery, accuracy of advanced non-invasive hemodynamic monitoring is determined.

4. Cerebral Perfusion
The main aim of this research line is to unravel the effect of oxygen on brain blood flow regulation. The results have important implications for amongst others the understanding and treatment of acute mountain sickness. For the treatment of patients with compromised cerebral autoregulation (CA) and oxygenation of the brain our studies evaluate (d) the importance of arterial hypertension and/or oxygen administration. Employing Near Infra-Red Spectroscopy (NIRS) to monitor cerebral tissue oxygenation, the role of oxygen in CA during changes in blood pressure or different levels of arterial blood oxygenation will be determined. Using new self-developed analysing techniques, we are able to quantify the ability of the cerebral vasculature to counter-regulate sudden changes in blood pressure, which occur frequently in the perioperative setting. Vasoactive medication, intravenous and volatile anesthetics influence autonomic nervous system activity and thereby result in considerable changes in blood pressure and alteration of the systemic cardiovascular regulation. Sympathetic nerves richly innervate cerebral vessels, but there is controversy about the role of sympathetic nerves in regulation of cerebral blood flow (CBF). Leaving all other regulatory mechanisms of CA unaffected we will create a cerebral sympathetic activity “knock out” model by blocking the superior stellate ganglion (SGB) unilaterally to quantify sympathetic contribution to the regulation of cerebral blood flow (CBF). If the regulation of the cerebral blood flow deteriorates during sympathetic blockade, the brain could be extra vulnerable to a decrease in blood pressure during the use of anesthetics. In addition, we will investigate the influence of changes in cerebral perfusion pressure and cerebral blood flow on CA in patients undergoing cardiac surgery with extracorporeal bypass, with and without pre-existing diseases (such as diabetes, stroke etc.).

5. Decision Support
Clinical guidelines are a commonly used means to translate scientific evidence to good clinical care. They serve many purposes, but are generally agreed on to get the right (state of art) treatment for the right patient, reduce uncontrolled variation and improve clinical care. However, in practice, the implementation of guidelines may be limited by poor adherence. The aim of this project is to investigate which factors that influence non-adherence to guidelines can be addressed by using decision support as an integrated system within the Patient Data Management System.  This system constantly monitors the data in the patient record and provides assistance in recognizing or even predicting potential complications and impending non-adherence and provide decision assistance with as little disruption of clinical care as possible. We proved that these systems can improve guideline adherence and can improve quality of care for a specific guideline and now aim to expand the system and optimize it to be more robust and applicable to other guidelines and situations. Moreover, we will look in to unintended consequences of decision support and reasons for residual non-adherence.

6. Sedation - safety and effectivity
In cooperation of the Departments of Anesthesiology and the Departments of Gastroenterology & Hepatology of the Academic Medical Center, Amsterdam and the University Medical Center Utrecht, this research line focuses on the differences in patient safety and satisfaction, effectivity and experiences by the gastroenterologists when sedation is given by a sedation anesthesia nurse (SAN), experienced in airway management, or a gastroenterologist, who is doing the gastroenterological procedure at the same time. A nationwide safety project evaluated the possible complications in more than 12000 sedated patients.

7. Big data and Patient Monitoring using Novel techniques
The future of science lies in the collaboration between research groups and departments. The Department of Anesthesiology at the AMC is one non-US divisions to join the Multicentre Perioperative Outcomes Group (MPOG) project (Dr. P. Lirk, Drs. F. Kooij), and we have uploaded our first data the „Anesthesia Quality Institute (AQI)“ of the American Society of Anesthesiology (ASA). We are actively contributing towards MPOG research projects, and have submitted our first Research Proposal to the MPOG Research Committee.
In addition, we are exploring the potential clinical benefits of wireless monitoring of surgical (high-risk) patients using a new RFID technology (Sensium^®), and have recently been awarded an Innovative Patient Care project grant to investigate how this monitoring might influence the “failure to detect” of the surgical patient, and thereby improve patient outcome.