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Eindhoven, Netherlands

de Hart J.,HemoLab Cardiovascular Engineering | Weger A.,Leiden University | van Tuijl S.,HemoLab Cardiovascular Engineering | Stijnen J.M.A.,HemoLab Cardiovascular Engineering | And 4 more authors.
International Journal of Artificial Organs

Purpose: Cardiac research and development of therapies and devices is being done with in silico models, using computer simulations, in vitro models, for example using pulse duplicators or in vivo models using animal models. These platforms, however, still show essential gaps in the study of comprehensive cardiac mechanics, hemodynamics, and device interaction. The PhysioHeart platform was developed to overcome these gaps by the ability to study cardiac hemodynamic functioning and device interaction ex vivo under in vivo conditions. Methods: Slaughterhouse pig hearts (420 ± 30 g) were used for their morphological and physiological similarities to human hearts. Hearts were arrested, isolated and transported similar to transplantation protocols. After preparation, the hearts were connected to a special circulatory system that has been engineered using physical and medical principles. Through coronary reperfusion and controlled cardiac loading, physiological cardiac performance was achieved while hemodynamic parameters were continuously monitored. Results: Normal cardiac hemodynamic performance was achieved both qualitatively, in terms of pulse waveforms, and quantitatively, in terms of average cardiac output (4 l/min) and pressures (110/75 mmHg). Cardiac performance was controlled and kept at normal levels for up to 4 hours, with only minor deterioration of hemodynamic performance. Conclusions: With the PhysioHeart platform we were able to reproduce normal physiological cardiac conditions ex vivo. The platform enables us to study, under different but controlled physiological conditions, form, function, and device interaction through monitoring of performance parameters and intra-cardiac visualization. Although the platform has been used for pig hearts, application of the underlying physical and engineering principles to physiologically comparable hearts from different origin is rather straightforward. Source

Tuzun E.,Texas A&M University | Tuzun E.,TU Eindhoven | Pennings K.,TU Eindhoven | van Tuijl S.,TU Eindhoven | And 5 more authors.
European Journal of Cardio-thoracic Surgery

Objectives: Aortic valve regurgitation, fusion and thrombosis are commonly reported clinical complications after continuous flow ventricular assist device implantations; however, the complex interaction between reduced pulsatile flow physiology and aortic valve functions has not been studied experimentally. To address this, a continuous flow left ventricular assist device was implanted in four swine ex vivo beating hearts and then operated at baseline (device off, no flow) and at device speeds ranging between 8500 and 11 500 rpm under healthy and experimentally created failing heart conditions. Methods: At baseline and after each speed increase, aortic, left ventricular, left atrial and pulse pressure signals were monitored to assess the haemodynamic status of the ex vivo heart, aortic valve opening time and the transvalvular pressure changes. Aortic root and device flows were recorded with flow probes. Left ventricular pressure-volume loops were measured with a conductance catheter. Changes in aortic leaflet motion and end-diastolic aortic root diameter were recorded with epicardial echocardiography. Results: A two-chamber healthy and failing ex vivo beating heart model was successfully created. At increasing device flows, aortic valve open time steadily decreased from 36 ± 7% of the baseline cardiac cycle to 0% at 11 500 rpm in the healthy heart and from 18 ± 16 to 0% in failing heart mode (P < 0.05). Aortic transvalvular pressure increased from 25 ± 5 mmHg (baseline) to 67 ± 7 mmHg (11 500 rpm) in the healthy heart and from 10 ± 9 mmHg (baseline) to 73 ± 8 mmHg (11 500 rpm) in failing heart mode (P < 0.05). Aortic root diameters were significantly increased at speeds exceeding 10 500 rpm in the healthy heart mode (P < 0.05 vs baseline) and approached statistical significance in failing hearts. Conclusions: Increasing assist device flows resulted in pressure overload above the aortic leaflets, impaired leaflet functions, caused aortic root dilatation and altered leaflet coaptation at the central portion of the aortic valve in both modes. We conclude that the deleterious effect of the reduced pulsatile flow on the aortic valve functions and haemodynamics is immediate and such an insult may explain the structural changes of the aortic valve causing leaflet fusion and/or regurgitation in the chronic phase. © The Author 2013. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved. Source

Schampaert S.,TU Eindhoven | van 't Veer M.,TU Eindhoven | Rutten M.C.M.,TU Eindhoven | van Tuijl S.,HemoLab Cardiovascular Engineering | And 3 more authors.
Artificial Organs

The isolated beating pig heart model is an accessible platform to investigate the coronary circulation in its truly morphological and physiological state, whereas its use is beneficial from a time, cost, and ethical perspective. However, whether the coronary autoregulation is still intact is not known. Here, we study the autoregulation of coronary blood flow in the working isolated pig heart in response to brief occlusions of the coronary artery, to step-wise changes in left ventricular loading conditions and contractile states, and to pharmacologic vasodilating stimuli. Six slaughterhouse pig hearts (473±40g) were isolated, prepared, and connected to an external circulatory system. Through coronary reperfusion and controlled cardiac loading, physiological cardiac performance was achieved. After release of a coronary occlusion, coronary blood flow rose rapidly to an equal (maximum) level as the flow during control beats, independent of the duration of occlusion. Moreover, a linear relation was found between coronary blood flow and coronary driving pressure for a wide variation of preload, afterload, and contractility. In addition, intracoronary administration of papaverine did not yield a transient increase in blood flow indicating the presence of maximum coronary hyperemia. Together, this indicates that the coronary circulation in the isolated beating pig heart is in a permanent state of maximum hyperemia. This makes the model excellently suitable for testing and validating cardiovascular devices (i.e., heart valves, stent grafts, and ventricular assist devices) under well-controlled circumstances, whereas it decreases the necessity of sacrificing large mammalians for performing classical animal experiments. © 2013 Wiley Periodicals, Inc. and International Center for Artificial Organs and Transplantation. Source

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