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FRIMEDBIO-Fri prosj.st. med.,helse,biol

Cardiac stroke volume and its contribution to the circulation: Interaction of mechanical and nervous factors affecting the heart

Awarded: NOK 2.9 mill.

When breathing, the heart is affected by nervous and mechanical factors. In my project I have investigated the interaction between nervous and mechanical contribution on the cardiac stroke volume. I have developed and published a new method to measure the cardiac stroke volume from both the right and left side of the heart simultaneously. With this method I have investigated how changes in the filling of the heart affect the cardiac stroke volume and which interaction there is between the right and left s ides of the heart. The paper in which this method is described was awarded the Carl Ludwig prize for best paper by young scientist in Acta Physiologica in 2012. In a recent study I have measured cardiac stroke volume from right and left side of the heart in healthy subjects with non-invasive methods during non-invasive intermittent positive pressure ventilation and compared with spontaneous breathing. In addition we have investigated the cardiac stroke volume and its variations during a simulated hemorrh age in healthy subjects. Cardiac stroke volume variations are clinically in use to monitor hypovolemia. In a third study we have combined simulated hemorrhage and intermittent positive pressure ventilation. All studies are under analysis or submitted, and are presented at international conferences. I spent at the University of Bristol, UK, in professor Marianne Thoresen?s group. This year of my postdoc training I learnt several new techniques and participated in the world?s first clinical study of the no ble gas xenon for treatment of birth asphyxia. That study showed that is feasible to treat asphyxiated neonates with xenon and further randomized clinical trials have been initiated. Standard care of asphyxiated neonates is hypothermia treatment to core t emperature of 33.5°C for 72 hours. We aim to improve treatment for this group, and find predicting markers of good and poor outcome. We have found that a marker on brain circulation is no longer valid for predicting poor neurological outcome during hypoth ermia treatment.

Cardiac output is one of the most important factors determining the circulatory state in both healthy subjects and patients. Cardiac output is determined by heart rate and stroke volume. Heart rate changes in healthy humans and patients are well character ised, while more knowledge is needed about stroke volume changes in humans. This project will investigate the contribution of cardiac stroke volume to the circulation in healthy humans. Stroke volume may be altered by at least four mechanisms: 1) a chang e in venous return, 2) a change in contractility, 3) adjustment of filling time due to a change in heart rate, and 4) a change in the afterload effect. These four mechanisms interact, the first two generally tending to counteract the latter two, and their combined effects determine whether stroke volume changes contribute to or counteract changes in cardiac output. The main objective of the project is to investigate how mechanical (1 and 4) and neural (2 and 3) factors interact and affect cardiac stroke volume in healthy humans. We hypothesise that in general, neural regulation counteracts potentially unfavourable mechanical factors, and that the complex interactions between respiration and circulation are optimised in healthy subjects. This project will study A) the interaction between the right and left sides of the heart, and B) the interaction between the afterload effect and the arterial baroreflex. Integrated human cardiovascular physiology provides insight into the circulation which is of intrins ic value and can be translated into advances in pathology and patient care. The results will benefit patients suffering from cardiovascular disease and those with compromised circulation. Malfunctioning of control mechanisms in the human circulation may l ead to diseases. Knowledge of the cardiovascular control mechanisms in healthy humans is applicable to most patient groups, and advances in our understanding of such mechanisms will improve clinical practice.

Publications from Cristin

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FRIMEDBIO-Fri prosj.st. med.,helse,biol

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