Projects / Programmes
Effects of new methods in cardiac surgery
Code |
Science |
Field |
Subfield |
7.00.00 |
Interdisciplinary research |
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Code |
Science |
Field |
B007 |
Biomedical sciences |
Medicine (human and vertebrates) |
Code |
Science |
Field |
3.02 |
Medical and Health Sciences |
Clinical medicine |
cardiopulmonary bypass, minimal invasive surgery, immune response, adsorption, emboli, cerebral blood flow, neurological complications
Researchers (31)
Organisations (2)
Abstract
Background: Although cardiopulmonary bypass (CPB) is indispensable for most open heart surgery, its use is associated to unwanted systemic inflammatory response. This complex chain of events has many similarities with sepsis and may contribute to the development of postoperative complications, all the way to multiple organ failure and death. It was shown that CPB can also trigger an anti-inflammatory response. The balance of inflammatory and anti-inflammatory mediators determines inflammatory response and clinical outcome. Considerable efforts have been focused on therapeutic interventions to reduce the inflammatory reaction related to CPB, including pharmacological strategies, i.e.use of corticosteroids, and improvment in surgical techics or mechanical devices. Such therapies may have positive effects on outcome of patients after open heart surgery. Serum paroksonaza 1 (PON1) is a lipo-laktonaza being associated with HDL, which has anti-inflammatory role. Exosomes are nanovesicles released from cells and are mediators of proximal as well as distant cell-to-cell signaling. The question is, what is clinical importance of non-selective artificial imunoadsorbtion during CPB, focusing specially on PON1 and exosomes.
Brain injury after aortic valve replacement (AVR) includes stroke, coma, encephalopathy, delirium and cognitive decline. Intraoperative cerebral embolization appears to be an important mechanism of such injury, as gaseous or solid cerebral emboli can cause ischemia, inflammation and edema, consequently causing cerebral microinfarctions.
AVR by way of a full sternotomy (FS) is the standard approach in the treatment of aortic valve disease. Another approach is when surgeon performes AVR through partial sternotomy, this is minimally invasive surgery (MIS). Compared with conventional surgery (FS), MIS has been shown to reduce postoperative mortality, morbidity, and pain while providing faster recovery, a shorter hospital stay, and better cosmetic results. However, due to technically more demanding procedure, MIS may lead to prolonged CPB time and incomplete aorta de-airing with an increased risk for cerebral gas embolization. Therefore, the choice of MIS might bear an augmented risk for brain injury. Cerebral microembolic signals (MES) may be detected in real time with transcranial Doppler ultrasound (TCD).
Research objectives: Our aim is to improve cardiosurgical techniques, to minimaze proinflamatory response after CPB and decrease the decline of cognitive functions. The purpose of research, conducted at the Clinical Department of Cardiovascular Surgery at the University Medical Centre Ljubljana, is to analyze the effect of selective in vitro imunoadsobtion on development of inflammatory immune to answer and of protective mechanisms of CPB in cardiac surgery.The second aim is comparison of two surgical techniques for AVR. We will specially focus on intraoperative MES, level of S100B protein (marker of brain injury), postoperative cerebrovascular reactivity and cognitive function.
Significance for science
We believe that results of our study will remarkable contribute to understandings of the inflammatory response induced in complex cardiac surgery with the use of cardio-pulmonary bypass (CBP). Immuno-adsorbtion during CPB will be an effective method for reducing the concentration of pro inflammatory and anti-inflammatory mediators between cardiac surgery, but will not have a negative impact on other protection mechanisms, i.e. the activity of PON1. We expect immuno-adsorption during complex cardiac surgery with CPB will become an everyday routine in the future. Because corticosteroids, probably producing prolonged immune paralysis, we will need to change the daily routine and to withdraw corticosteroids from liquid for preparing CPB (priming solution).
We expect the high incidence of detected micro emboli in the cerebral vasculature during open heart surgery, but there will probably be no statistically significant difference between minimally invasive surgery compared to full sternotomy. We expect that the frequency of brain micro embolisms will be associated with biochemical signs of brain injury (i.e. increased S100B), impaired cerebral vascular reactivity and cognitive dysfunction. In this case it will be necessary to consider the development of additional procedures to prevent brain micro-embolization; such possibilities are open heart surgery in locally modified gas mixture or additional mechanical protection of brain circulation.
Significance for the country
An estimated 17.3 million people died from cardiovascular disease (CVDs) in 2008. By 2030 more than 23 million people will die annually from CVDs ; this estimation was done by World Health Organization (WHO) (http://www.who.int/cardiovascular_diseases). All 194 members of WHO have accepted Global action plan for the prevention and control of Noncommunicable diseases and mental health 2013-2020 (including cardiovascular diseases, cancer, chronic respiratory diseases and diabetes). When prevention does not help anymore, we have to treat CVDs, surgical treatment is the most complex especially when CPB must be used. With reducing cytokine storm during CPB, we expect more stable patients, with less secondary infections leading to shorter intensive care stay, shorter hospital stay and lower mortality. These all will result in lower economic burden of health system per person treated. There is not just mortality which matters, morbidity and quality of life of patients with after surgery is also very important. Exploring the causes for neurological dysfunction and cognitive impairment after cardiac surgery, we could improve our techniques, which could results in better neurological outcome and also to more healthy population after surgery. In the development of new techniques to protect the brain during CPB we could cooperate with interested companies.
Most important scientific results
Final report
Most important socioeconomically and culturally relevant results
Interim report,
final report