Ion Channel Regulation by Estrogen
Seminar Room 1, Newton Institute
Due to the mutual interaction between cardiac contraction and variations in pre- and after-load, experimental validation studies of mathematical modeling of the heart and the coronary circulation seem to be restricted to in-vivo animal- or patient-studies and hereby are hampered by ethical regulations as well as by the complexity of the in-tact in-vivo system. We aim to partly overcome these limitations by developing phantom and ex-vivo experimental platforms that mimic the cardiovascular system as close as possible and provide good accessibility to imaging- and sensor-based measurement equipment.
The phantom circulation-loop features a control mechanism based on a heart model defined by a Hill-type muscle contraction and is capable of adapting its contractile behavior as a function of time, ventricular volume and ejection rate. The heart rate is controlled by a baroreflex model that describes the heart rate as a function of systemic blood pressure and time. By real-time monitoring of systemic blood-pressure in an extended windkessel-type mock-loop and control of heart rate and stroke volume a pressure-volume loop that physiologically responds to external variations can be realized. A specially designed module for coronary flow dependent on systemic and ventricular pressure completes the system.
In the ex-vivo platform, slaughterhouse pig hearts (420 Ī 30 g) were isolated, arrested and transported according to human transplantation protocols. After preparation the isolated hearts were connected to a special circulatory system, that has been engineered to enable physiological cardiac performance using physical and medical principles while coronary flow was reinstated. The platform allows to either choosing a Langendorff mode, a 2- or 4 chamber working heart mode or a heart-lung mode. Hemodynamic function in terms of cardiac output, aortic pressures, ventricle pressures, dP/dt, heart rate, and coronary flow can be monitored and controlled and allows not only to achieve physiological cardiac electromechanical and hemodynamic responses but also to vary cardiac/hemodynamic performance for at least 3 hours, while surgical and interventional procedures can be carried out.