Biomedical subjects

Willem Flameng

Publications and source records attributed to Willem Flameng.

42 records · Page 3Linked to original sources

PubMed2002

Design of a new pulsatile bioreactor for tissue engineered aortic heart valve formation.

Evidence has been gathered that biomechanical factors have a significant impact on cell differentiation and behavior in in vitro cell cultures. The aim of this bioreactor is to create a physiological environment in which tissue engineered (TE) aortic valves seeded with human cells can be cultivated during a period of several days. The bioreactor consists of 2 major parts: the left ventricle (LV) and the afterload consisting of a compliance, representing the elastic function of the large arteries, and in series a resistance, mimicking the arterioles and capillaries. The TE aortic valve is placed between the LV and the compliance. With controllable resistance, compliance, stroke volume and frequency, and hydrodynamic conditions can be changed over a wide physiological range. This study resulted in a prototype of a compact pulsatile flow system for the creation of TE aortic valves. In addition a biocompatibility study of the used materials is performed.

Aortic Valve↗

PubMed2002

Valved jugular vein segments for right ventricular outflow tract reconstruction in young sheep.

OBJECTIVE: This study was undertaken to investigate the degeneration and calcification of valved bovine jugular vein segments for right ventricular outflow tract reconstruction in juvenile sheep. METHODS: Seven valved bovine jugular vein conduits (Contegra model 220; VenPro Corporation, Irvine, Calif) and 3 control conduits (MH100; Medtronic, Inc, Minneapolis, Minn) were implanted in the pulmonary artery in young sheep. After 20 weeks the conduits were explanted and qualitatively analyzed by epicardial echocardiography, gross examination, x-ray analysis, light microscopy, and transmission electron microscopy. Calcification was determined quantitatively by flame atomic absorption spectrometry. RESULTS: Two Contegra conduits could not be analyzed because of endocarditis. All other Contegra conduits functioned well, with preserved structure and minimal calcification. The control MH100 conduits exhibited extensive fibrous sheathing, with calcification of the aortic wall portion and the commissural part of the Hancock valve. CONCLUSIONS: The Contegra conduit's performance was clearly superior to that of the control MH100 conduit when implanted in the pulmonary artery position in juvenile sheep for 5 months.

Animals↗

PubMed2002

Channels involved in transient currents unmasked by removal of extracellular calcium in cardiac cells.

In cardiac cells that lack macroscopic transient outward K(+) currents (I(to)), the removal of extracellular Ca(2+) can unmask "I(to)-like" currents. With the use of pig ventricular myocytes and the whole cell patch-clamp technique, we examined the possibility that cation efflux via L-type Ca(2+) channels underlies these currents. Removal of extracellular Ca(2+) and extracellular Mg(2+) induced time-independent currents at all potentials and time-dependent currents at potentials greater than -50 mV. Either K(+) or Cs(+) could carry the time-dependent currents, with reversal potential of +8 mV with internal K(+) and +34 mV with Cs(+). Activation and inactivation were voltage dependent [Boltzmann distributions with potential of half-maximal value (V(1/2)) = -24 mV and slope = -9 mV for activation; V(1/2) = -58 mV and slope = 13 mV for inactivation]. The time-dependent currents were resistant to 4-aminopyridine and to DIDS but blocked by nifedipine at high concentrations (IC(50) = 2 microM) as well as by verapamil and diltiazem. They could be increased by BAY K-8644 or by isoproterenol. We conclude that the I(to)-like currents are due to monovalent cation flow through L-type Ca(2+) channels, which in pig myocytes show low sensitivity to nifedipine.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

PubMed2002

Tissue engineering of an auto-xenograft pulmonary heart valve.

To improve the durability of stentless valves without losing their excellent hemodynamic function, a new-generation auto-xenograft was developed and evaluated. A piece of vein was harvested from 3 juvenile sheep 6 weeks before implantation of the valve. Endothelial cells from the vein material were cultivated and used to reendothelialize a decellularized porcine pulmonary valve. The tissue-engineered valve was implanted into the right ventricular outflow tract of the juvenile sheep. It was explanted after 100 days and assessed macroscopically as well as by x-ray, light microscopy (hematoxylin and eosin staining and von Kossa staining), and scanning electron microscopy. Calcium content of the cusps was determined quantitatively by atomic absorption spectrometry. The sheep implanted with the valve recovered quickly without any problems during the observation period. X-ray examination of the 3 explanted valves showed no cusp calcification, which was confirmed by histological study. Atomic absorption spectrometry showed low tissue calcium content. A clinical safety and feasibility trial with an allograft valve prepared the same way showed excellent short-term results in 6 patients.

Adult↗

PubMed2002

Myocardial blood flow, metabolism, and inotropic reserve in dogs with dysfunctional noninfarcted collateral-dependent myocardium.

UNLABELLED: There is intense controversy as to the mechanisms underlying chronic but reversible left ventricular (LV) ischemic dysfunction. The aim of this study was to investigate the physiology underlying this condition in a canine model of noninfarcted collateral-dependent myocardium. METHODS: Six mongrel dogs were instrumented with ameroid constrictors on the left circumflex and right coronary arteries and a partial occluder on the left anterior descending coronary artery. The animals were followed up for 6 mo. Every 6 wk, measurements of regional wall thickening (M-mode echo), myocardial blood flow ((13)N-ammonia PET), oxygen consumption ((11)C-acetate PET), and glucose uptake ((18)F-FDG PET) were obtained. After 6 mo, myocardial blood flow reserve (during adenosine infusion) and regional contractile reserve (during infusion of a low dose of dobutamine) were also investigated. RESULTS: Following ameroid implantation, regional thickening decreased in the posterior wall (to 34% +/- 13% of baseline; P < 0.001) but not in the septum. Resting myocardial blood flow (56 +/- 10 vs. 58 +/- 15 mL.[min.100 g](-1)), myocardial oxygen consumption (21 +/- 3 vs. 22 +/- 3 J.[beat.100 g](-1)), and insulin-stimulated glucose uptake (39 +/- 8 vs. 42 +/- 11 micromol.[min.100 g](-1)) were similar among dysfunctional and normal segments. Myocardial blood flow reserve was blunted in dysfunctional versus normal segments (3.7 +/- 0.5 vs. 5.2 +/- 1.5; P = 0.06). With dobutamine, wall thickening (to 69% +/- 8% and 77% +/- 11%, respectively) and oxygen consumption (to 36 +/- 5 and 39 +/- 5 J.[beat.100 g](-1), respectively) improved to the same extent in both segments. As a consequence, mechanical efficiency decreased in septal but remained unchanged in posterior segments during infusion of dobutamine. Biopsy specimens from both walls were free from any morphological alterations. CONCLUSION: Our data indicate that ameroid occlusion in dogs induces sustained reduction in regional contraction, which occurs despite normal levels of transmural blood flow and recruitable inotropic reserve. Since myocardial perfusion reserve was blunted, such perfusion-contraction mismatch could reflect repetitive stunning.

Animals↗

PubMed2000

A nonsurgical porcine model of left ventricular dysfunction. Validation of myocardial viability using dobutamine stress echocardiography and positron emission tomography.

BACKGROUND: Although several short-term animal models of stunning and hibernation have been studied extensively, it has been difficult to produce a consistent animal model of chronic hibernation. The aim of the present study was to develop a nonsurgical porcine stent model of coronary stenosis in order to investigate the relationship between chronic dysfunctional myocardium and viability using 2D-echo, dobutamine stress echo (DSE) and positron emission tomography (PET). METHODS AND RESULTS: Focal progressive coronary stenosis was induced by implantation of an oversized stent in the left anterior descending (LAD) and/or circumflex (LCX) coronary artery in a total of 115 pigs, according to various experimental protocols: copper stent in the LAD (group I, n = 5); noncoated stainless steel stent in the LAD combined with balloon overstretch (group II, n = 7); poly(organo)phosphazene-coated stent in the LAD (group III, n = 77); and poly(organo)phosphazene-coated stent in both the LAD and the LCX (group IV, n = 26). Occurrence of left ventricular dysfunction was evaluated weekly by 2D-echo. At the time of left ventricular dysfunction the presence of viable myocardium within the dysfunctional region was investigated with DSE and PET, and confirmed by histology. The degree of coronary artery stenosis was measured by quantitative coronary angiography and morphometry. Severe coronary artery stenosis in the presence of dysfunctional, but viable, myocardium was induced in groups III and IV (47% and 11% of the animals, respectively). CONCLUSIONS: The authors developed a nonsurgical porcine stent model of progressive coronary stenosis using an oversized polymer-coated stent resulting in chronically decreased myocardial function, with residual inotropic reserve and viable myocardium. This condition may arise from repetitive periods of ischemia, or from sustained hypoperfusion, or a combination of these processes eventually leading to myocardial hibernation.

Journal Article↗