The research group within cardioprotection and myocardial metabolism uses small and large animal models to study the molecular basis and modulation of metabolism in cardioprotection against ischemia/reperfusion injury.
In-vivo as well as in-vitro models, including the Langendorff model in mice, rats and rabbits are established in our small animal laboratory, while in-vivo porcine models are used in our large animal research facility.
A human atrial strip model is established to translate findings into preclinical models.
Evaluation of cardiac function using non-invasive imaging, including echocardiography and NMR, and invasive techniques including conductance and high fidelity pressure catheters, is established in all in-vivo models. Evaluation of myocardial metabolism takes advantage of isotopical tracer techniques and is evaluated in blood samples, myocardial biopsies and interstitial fluid obtained by microdialysis.
Our in-vivo and in-vitro models have been established in animals with and without pre-existing disease, i.e. diabetes, and in animals of different ages. In our molecular laboratory a variety of methods including Western Blot, PCR and mass spectroscopy have been established to support studies of the metabolic mechanisms underlying cardiovascular disease and cardioprotection.
This metabolic molecular approach is used at cytosolic and mitochondrial levels. Using tracer technique we investigate the importance of myocardial glucose uptake, glycolytic flux and glucose oxidation in cardioprotection. Furthermore, accessory glycolytic pathways involved in post-translational modifications by glycosylation of proteins, O-linked N-acetylglucosamine, are investigated. Involvement of myocardial amino acid metabolism in myocardial protection is investigated using exogenous glutamate and glutamine supplementation and drugs influencing endogenous glutamate metabolism. The metabolic links and pathways for communication of bioenergetics states between the cytosolic and mitochondrial compartments are investigated with focus on the malate-aspartate shuttle.
Cardioprotection by activation of innate cellular protective mechanisms, can be induced before, during or after an ischemic insult. Cardioprotection induced by short intermittent episodes of ischemia, ischemic pre-, per- and post-conditioning, may be induced locally in the heart or at remote sites. Because an acute myocardial infarction is unpredictable, we have focused our translational research on remote per-conditioning. This approach is feasible and beneficial in the treatment of patients undergoing primary angioplasty for a ST-elevation acute myocardial infarction.
Other areas of interest for research include right ventricular failure and pulmonary hypertension, effects of oral anti-diabetic drugs on myocardial metabolism, effect of cardiac resynchronisation therapy on myocardial metabolism and the effect of metabolic alterations on cardiac arrythmogenicitity.
The laboratory research facilities are provided in a collaboration between the Department of Clinical Medicine, Aarhus University and the Department of Cardiology, Aarhus University Hospital.
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