Göran Rådegran

Hemodynamic Control - Influence of Cardiovascular and Pulmonary disease, Environmental conditions, Exercise and Treatments including Transplantation

Research group and Project presentation

Background

Hemodynamic adjustments and alterations of vascular tone is a prerequisite to increase cardiac output and blood flow, to meet the elevated metabolic demands that is imposed by exercise, various environmental conditions and states of diseases. Many diseases are also characterized by an impaired hemodynamics as well as structural alterations of the vasculature. Furthermore, in the pulmonary circulation, pulmonary hypertension may develop, related to 1.) pulmonary arterial hypertension (PAH), 2.) left heart disease, 3.) lung disease and/or hypoxia, 4.) chronic thromboembolism, or be due to 5.) unclear and/or multifactorial mechanisms. PAH, specifically, is characterized by, an imbalance between vasoconstrictors and vasodilators, as well as vascular modifications including medial hypertrophy, intimal proliferation, fibrotic changes, adventitial thickening, peri-vascular inflammatory infiltrates, complexiform and thrombotic lesions. Whereas the development of treatments for coronary artery disease, systemic hypertension and heart failure, has developed markedly, the outcome in patients with PAH still remains poor, exhibiting untreated a median survival at diagnosis of only 1-2,8 years depending on its cause. Furthermore, with respect to severe heart failure, organ availability for transplantation remains low. To improve clinical outcome, further research is a necessity, to enable earlier disease detection, as well as for initiation of proper and individualized treatment at a correct timing.

Aim

The present projects aim to adress; the mechanisms that impair hemodynamics; and the factors that control and alter vascular tone in lungs, cardiac- and skeletal muscle, during rest and exercise, in normoxia and hypoxia, in health and disease; as well as identify biomarkers of cardiopulmonary disease; in order to develop new and individualized treatments and diagnostic procedures for patients with cardiovascular & pulmonary circulatory diseases.

Methods

Interdisciplinary research is performed in a translational manner from animals, to healthy humans and patients with cardiovascular and pulmonary disorders, such as; pulmonary and systemic hypertension and heart failure. Blood sampling, myocardial biopsies and hemodynamic monitoring are performed and evaluated in our clinical investigations of selected patients with severe heart failure and pulmonary hypertension, prior to and after transplantation or treatment with medical therapy and/or mechanical assist devices, the latter utilising the Swan Ganz technique, echocardiography and/or magnetic resonance imaging. Pulmonary scintigraphy is used to address pulmonary circulation and ventilation.

To facilitate cardiovascular research collaborations in the Öresund region, “The Öresund Cardiovascular Research Collaboration” has been initiated. Studies may be performed utilising our hypoxic pulmonary vasoconstriction porcine model at the Panum institute (Copenhagen, Denmark) or BMC (Faculty of Medicine, Lund University), healthy human exercise model at CMRC (Rigshospitalet, Copenhagen, Denmark) and patient exercise model at our hemodynamic laboratory (SUS, Lund, Sweden). With the aim to facilitate transplantation research, Lund Heart Transplantation Research Network has been initiated 2011. Further collaborative projects may be initiated with Hospital Antoine Beclere and Marie Lannelongue hospital in Paris, France, eg. two expert centres on PAH, chronic thrombo-embolic pulmonary hypertension (CTEPH) and lung transplantations, to enable animal studies with regards to a  chronic thrombo-embolic porcine- and monocrotaline PAH rat model.

Ongoing Projects

1. Mechanisms controlling vascular tone in health and disease

- Modulators of Hypoxic Pulmonary Vasoconstriction and Pulmonary Hypertension - Implications for new treatments

- Regulation of skeletal muscle hyperaemia in normoxia and hypoxia in health and disease

2. Hemodynamic consequences of heart failure and pulmonary hypertension

- Pulmonary hypertension - Mechanisms, new treatments and diagnostic procedures

- Hemodynamic consequences of heart failure and pulmonary hypertension - Influence of medical treatment, including mechanical assist devices and transplantation

- Novel measurements of cardiac output and blood flow in patients with heart failure and pulmonary hypertension as well as healthy individuals

3. Metabolic and clinical determinants of heart- and pulmonary vascular function.

- “Lund Cardio Pulmonary Registry” - Blood samples from our hemodynamic laboratory of patients with pulmonary hypertension and severe heart failure, prior to and after treatment with medical therapy, heart- and/or lung transplantation, and/or mechanical assist devices, are stored in Region Skånes Biobank, with the aim to; identify new biomarkers (eg. proteins, microRNA’s etc…) for disease detection, differential diagnosis, prognosis, and evaluation as well as monitoring of treatments; and potentially for identification of genetic markers of risk populations for pulmonary hypertension and heart failure of various causes.

Disertation. Göran Rådegran. Human skeletal muscle hyperaemia: its magnitude and regulation during exercise, Copenhagen Muscle Research Centre, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark, Thesis defense Oct. 18, 2002

Project leader: Göran Rådegran

MD, dr med, M Sc Eng Physics, Docent/Associate professor

Project coordinator: Göran Rådegran, initiator of ÖCRC, Lund Cardio Pulmonary Registry and Lund Heart Transplantation Research Network

Present Collaborators: Gustav Smith, Henrik Engblom, Ellen Ostenfeld, Johan Holm, Marcus Carlsson, Johan Nilsson, Jenny Öhman, David Erlinge, Björn Kornhall, Björn Ekmehag, Öyvind Reitan, Ylva Hellsten, Rob Boushel and Bengt Saltin, amongst others.

Research students: David Kylhammar, Annaeva Wiklund, Petter Hedelin, Jakob Lundgren