Willem Flameng | Katholieke Universiteit Leuven (original) (raw)
Papers by Willem Flameng
Journal of Thoracic and Cardiovascular Surgery, 1996
This experimental study was designed to assess the influence of failure of the right side of the ... more This experimental study was designed to assess the influence of failure of the right side of the heart or pulmonary hypertension, or both, on the performance of a novel miniaturized left ventricular assist device. In small-sized dogs (n = 50) ischemic global left ventricular failure was induced and support was provided by the HIA-VAD displacement pump (stroke volume 10 or 25 ml) installed as a left ventricular assist device. In three groups of animals (n = 10 each) pulmonary hypertension was created before induction of global left ventricular failure. During left ventricular assist device support temporary ischemic failure of the right side of the heart was induced in four groups of animals (n = 10 each). In the group subjected to left ventricular failure, support with the left ventricular assist device, and right ventricular failure during left ventricular assist, left atrial pressure and cardiac index were significantly lower than in the group subjected to left ventricular failure and left ventricular assist alone (2 +/- 6 versus 11 +/- 6 mm Hg and 1.6 +/- 0.4 versus 1.0 +/- 0.4 L/(min/m2), respectively, p < 0.05). In the group subjected to pulmonary hypertension, left ventricular failure, and left ventricular support, left atrial pressure dropped to values near zero but cardiac index remained unaltered as compared with results with the same regimen without pulmonary hypertension. However, when right ventricular failure was added (that is, pulmonary hypertension, left ventricular failure, left ventricular support, and right ventricular failure during support with the left ventricular assist device) left atrial pressure dropped to negative values (p < 0.05) and cardiac index progressively deteriorated. When, in an additional group of dogs, biventricular support was installed in the latter regimen, circulation was initially well supported but oxygenation deteriorated in 60% of cases. We conclude that (1) adequate right ventricular function was indispensable during support with the left ventricular assist device, (2) the combination of pulmonary hypertension and right ventricular failure led to the "low left ventricular assist device output syndrome," and (3) biventricular mechanical support in the presence of pulmonary hypertension may be complicated by the alveolar leakage syndrome.
Objectives: Free fatty acid (FFA) oxidation is depressed in the postischaemic stunned myocardium ... more Objectives: Free fatty acid (FFA) oxidation is depressed in the postischaemic stunned myocardium and recovers in pitmllel with the normalization 01 contracti Ie performance. Assuming a causal role for this metabolic disturbance in the ptitbogencsis of' stunning, wc questioned whether exogenous administration of' high dose triglycerides during repertirsion of postischaemic myocardium. could impm~e its functional recovery. Methods: Thirteen dogs were
Cardiovascular diabetology, 2012
The number of patients with diabetes or the metabolic syndrome reaches epidemic proportions. On t... more The number of patients with diabetes or the metabolic syndrome reaches epidemic proportions. On top of their diabetic cardiomyopathy, these patients experience frequent and severe cardiac ischemia-reperfusion (IR) insults, which further aggravate their degree of heart failure. Food restriction and angiotensin-converting enzyme inhibition (ACE-I) are standard therapies in these patients but the effects on cardiac IR injury have never been investigated. In this study, we tested the hypothesis that 1° food restriction and 2° ACE-I reduce infarct size and preserve cardiac contractility after IR injury in mouse models of diabetes and the metabolic syndrome. C57Bl6/J wild type (WT) mice, leptin deficient ob/ob (model for type II diabetes) and double knock-out (LDLR-/-;ob/ob, further called DKO) mice with combined leptin and LDL-receptor deficiency (model for metabolic syndrome) were used. The effects of 12 weeks food restriction or ACE-I on infarct size and load-independent left ventricul...
Repair of complex valve pathological processes often requires the use of leaflet tissue or perica... more Repair of complex valve pathological processes often requires the use of leaflet tissue or pericardium. The use of bovine photo-oxidized pericardium may be an alternative, a tissue less prone to calcification. The aim of this study is to evaluate the use of photo-oxidized bovine pericardial tissue in the reconstruction of atrioventricular valves in humans. Between July 2001 and September 2006,
Background—Hypercholesterolemia induces functional and structural changes of the microvasculature... more Background—Hypercholesterolemia induces functional and structural changes of the microvasculature and reduces coronary flow reserve in humans and experimental animals. The effect of hypercholesterolemia on left ventricular (LV) function in the absence of coronary stenosis is, however, unknown. Our objective was therefore to assess the effect of hypercholesterolemia and cholesterol withdrawal on LV function in the presence of advanced coronary plaques
The Japanese Journal of Thoracic and Cardiovascular Surgery, 2002
Ischemic preconditioning (PC) has been proposed as an endogenous form of protection against-ische... more Ischemic preconditioning (PC) has been proposed as an endogenous form of protection against-ischemia reperfusion injury. We have shown that PC does not prevent post-ischemic dysfunction in the aging heart. This phenomenon could be due to the reduction of cardiac norepinephrine release and it has also been previously demonstrated that age-related decrease of norepinephrine release from cardiac adrenergic nerves may be restored by caloric restriction.
Perfusion, 2002
Today, rotary pumps are routinely used for extracorporeal circulation in different clinical setti... more Today, rotary pumps are routinely used for extracorporeal circulation in different clinical settings and applications. A review of these applications and specific limitations in extracorporeal perfusion was performed and served as a basis for the development of the DeltaStream. The DeltaStreams is a miniaturized rotary blood pump of a new and unique design with an integrated drive unit. Despite its small design, the pump maintains a sufficient hydraulic capacity, which makes the DeltaStream very flexible for intra- and perioperative applications. It also opens the field for short-term ventricular assist devices (VAD) applications or use as a component in extracorporeal life support systems (ECLS). The DeltaStream and, specifically, its impeller design have been optimized with respect to haemolysis and nonthrombogenicity. Also, the pump facilitates an effective pulse generation in VAD applications and simulates heart action in a more physiological way than other rotary pumps or rolle...
The Journal of thoracic and cardiovascular surgery, 2015
Despite improved anticalcification technology, bioprosthetic heart valves still cannot be used in... more Despite improved anticalcification technology, bioprosthetic heart valves still cannot be used in younger patients because of progressive structural valve degeneration. A novel advanced tissue preservation technology was developed that uses stable functional group capping and preservation by glycerolization. Valves incorporating this novel technology can be stored in a dry condition and do not require rinsing before use. The aim of the study was to assess the effects of this new technology in terms of valve function and durability in a chronic sheep model of orthotopic implantation. Forty-five juvenile sheep were randomized and either a Perimount mitral valve (6900P, control group) or the same valve design incorporating the novel tissue preservation technology (test group) was implanted in the mitral position. All valves were 25 mm. A transthoracic echocardiography was performed at 1 week and at 8 months postoperatively. The animals were then killed, an autopsy was performed, and th...
The Journal of heart valve disease, 2010
Triple valve surgery remains a challenge, although with an improved survival rate compared to his... more Triple valve surgery remains a challenge, although with an improved survival rate compared to historical data. Aws assessment was made as to whether the type of valve surgery, underlying valve lesion and pathology were independent predictors of outcome. The patient characteristics were also described according to the type of surgery performed. A total of 166 consecutive patients underwent triple valve surgery and were followed up between October 1972 and June 2006. The clinical and operative variables were obtained retrospectively by physicians. The median follow up was 6.11 years (interquartile range 2.13-10.43). The overall 30-day mortality was 10%, five-year survival 70%, and 10-year survival 60%. In patients with three mechanical valves, survival at five years was 90%, and 85% at 10 years, compared to 40% at five years and 30% at 10 years in patients with three bioprostheses. Among all patients with a mechanical valve in the aortic and mitral positions, those with a tricuspid bi...
Verhandelingen - Koninklijke Academie voor Geneeskunde van België, 2008
Preconditioning is the most powerful endogenous mechanism, to protect the heart against ischemic ... more Preconditioning is the most powerful endogenous mechanism, to protect the heart against ischemic damage. Conflicting data are published whether preconditioning can be induced in case of diabetes and the metabolic syndrome, which are clinically very relevant conditions. If preconditioning could be induced consistently and chronically in this population, an important reduction of surgical morbidity and mortality could be reached. In this project we induced hypoxic preconditioning in mice and used cardiac pressure-conductance catheterisation and infarct size as outcome parameters. In the first part, we found that hypoxic preconditioning was capable to reduce infarct size with 40% and preserve the load-independent parameters with 33% after coronary occlusion. A DKO (double knock-out: ob/ob; LDLR-/-) model for the metabolic syndrome developed a larger infarct size and had a reduced contractility. No preconditioning could be induced in this model. To detect the determing factor of the res...
Physiological research / Academia Scientiarum Bohemoslovaca, 2008
Reactive oxygen species (ROS) have been implicated in the mechanism of postischemic contractile d... more Reactive oxygen species (ROS) have been implicated in the mechanism of postischemic contractile dysfunction, known as myocardial stunning. In this study, we examined protective effects of antioxidant enzymes, superoxide dismutase (SOD) and catalase, against ischemia/reperfusion-induced cardiac dysfunction and inhibition of Na+,K+-ATPase activity. Isolated Langendorff-perfused rabbit hearts were subjected to 15 min of global normothermic ischemia followed by 10 min reperfusion. The hearts treated with SOD plus catalase did not show significant recovery of left ventricular (LV) end-diastolic pressure compared with untreated ischemic reperfused hearts. Treatment with antioxidants had no protective effects on developed LV pressure or its maximal positive and negative first derivatives (+/-LVdP/dt). Myocardial stunning was accompanied by significant loss in sarcolemmal Na+,K+-ATPase activity and thiol group content. Inhibition of enzyme activity and oxidation of SH groups were not preven...
Tissue degeneration and calcification are the two chief obstacles to the successful application o... more Tissue degeneration and calcification are the two chief obstacles to the successful application of bioprosthetic heart valves. To enable the study of the durability of bioprosthetic heart valves and the efficacy of anti-calcification treatment, it has become necessary to develop animal models. The aim of this study is to validate a new model for implantation in the pulmonary position. Three juvenile sheep underwent implantation of Carpentier-Edwards pericardial valves in the pulmonary position (experimental group). These three valves were compared with three Carpentier-Edwards pericardial valves in the aortic position in patients which had been explanted due to primary tissue failure (clinical group). The valves were analyzed. The findings of macroscopic, X-ray and light microscopic examination were very similar between the two groups. Scattered irregular calcification was seen near the commissures and at the base of the cusps in both groups. Quantitative calcium content analysis showed that calcification of the cusps had progressed to almost the same degree in both groups (experimental group, 3.7+/-0.2 micro g/mg dry tissue; clinical group, 4.3+/-0.3; p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;0.05). In the experimental group, calcification in the commissural area of the cusp was pronounced (6.5+/-1.0). In the clinical group, calcification had also progressed in the commissural area of the cusp (6.0+/-1.5), and extended to the base area of the cusp (6.6+/-1.2). This model is promising for preclinical evaluation of bioprosthetic heart valves. The degree of calcification is not significantly different between our experimental results after three months of implantation in sheep and clinical results after 10 years of implantation in elderly patients. However, the pattern of calcification is somewhat different between the two groups.
The Japanese journal of thoracic and cardiovascular surgery : official publication of the Japanese Association for Thoracic Surgery = Nihon Kyōbu Geka Gakkai zasshi, 2003
Stent mounting of any bioprosthesis, induces a loss of mobility and reduces the effective valve o... more Stent mounting of any bioprosthesis, induces a loss of mobility and reduces the effective valve orifice. By contrast, for stentless procedures, the higher surgical technicality remains a major obstacle for many surgeons. In an attempt to facilitate the insertion of the stentless porcine aortic valve (Toronto SPV), we tried to alter the design by lowering the invasive profile at the depth of the sinuses on both coronary sites. This could theoretically facilitate the implant of the modified stentless valve with an easygoing single layer suture at the challenging subcoronary level and make it more attractive for every surgeon. Modifications of the standard model were done by lowering the profile at the depth of the sinuses on both coronary sites, whether by plication or excision of the protruding porcine aortic wall at the nadir of each coronary sinus. Nine juvenile sheep underwent implantation of stentless porcine aortic valves in pulmonary position: 3 standard Toronto SPV, 3 plicated...
The rat subcutaneous model reproduces clinically observed mineralization of bioprosthetic tissues... more The rat subcutaneous model reproduces clinically observed mineralization of bioprosthetic tissues. However, the effectiveness of antimineralization treatment can be overestimated in subcutaneous implants, since specimens using this model are not subjected to mechanical and dynamic stress or blood-surface contact. The purpose of this study was to evaluate the influence of blood contact on the calcification of bioprosthetic valves. Glutaraldehyde-pretreated porcine aortic valves were prepared. Aortic wall and cusp discs were implanted subcutaneously in six rats for 8 weeks and were implanted within the jugular vein wall in six sheep for 3 and 6 months (blood contact model). Tissue discs were analyzed by gross inspection, radiography and light microscopy. Calcium content was determined by atomic absorption spectrometry. X-ray and light microscopic examination showed calcification in the cusps to be higher than that in the aortic wall in the rat subcutaneous model. On the other hand, in the blood contact model, the cusps were slightly calcified and calcification in the aortic wall was more pronounced. Calcium analysis in rats revealed more calcium in the cusp than in the aortic wall (71.5+/-9.7 g/mg dry tissue vs. 53.7+/-2.6, p=0.09). Tests for calcium content of the jugular vein samples in sheep showed significantly more calcium in the aortic wall than in the cusp (3 months, 7.9+/-1.5 vs. 0.3+/-0.1, p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.0001; 6 months, 77.2+/-6.1 vs. 27.2+/-10.2, p=0.0002). In addition, aortic wall and cusp calcification significantly increased with time. These data suggest that the results from the rat subcutaneous model were completely opposite to those for the blood contact model. This study confirms the need to include blood contact as a factor in in vivo pre-clinical valve testing.
Several animal models are currently used to study bioprosthetic tissue calcification. The study a... more Several animal models are currently used to study bioprosthetic tissue calcification. The study aim was to evaluate the influence of species and environmental factors (blood contact and arterial pressure) on valve tissue mineralization. Glutaraldehyde-fixed porcine cusps and aortic wall samples were implanted subcutaneously in rats (n = 6) and sheep (n = 18). In sheep, similar samples were also implanted into the jugular vein (blood contact) and carotid artery (blood contact and arterial pressure). Tissue was explanted at intervals up to three months and evaluated macroscopically, and by X-radiography, light and electron microscopy and calcium content measurement. After eight weeks in the subcutaneous position, glutaraldehyde-fixed cusps were severely calcified in rats, but not in sheep (78.6 +/- 28.3 and 0.3 +/- 0.5 microg Ca/mg, respectively; p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001). Aortic wall samples were calcified in both species, but less in sheep (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001). In sheep, blood contact without arterial pressure (venous implants) significantly increased the calcification of cusp and even more of aortic wall tissue. Arterial pressure had no effect on calcification of aortic wall tissue. Major inter-species inconsistencies were found in valve tissue calcification after subcutaneous implantation. In sheep, blood contact increased tissue calcification significantly, mainly in aortic wall samples. Arterial pressure did not enhance mineralization of aortic wall tissue.
Valve tissue calcification has complex host, implant, and mechanical determinants. We studied the... more Valve tissue calcification has complex host, implant, and mechanical determinants. We studied the influence of species (rat v sheep), environmental factors (presence v absence of blood contact and arterial stress), and tissue cellularity (normal v acellularized tissue) on porcine aortic wall mineralization. Porcine aortic wall samples underwent standard glutaraldehyde-fixation or combined enzyme-detergent acellularization. Samples were implanted subcutaneously in rats (n = 8) and in juvenile sheep (n = 8). Furthermore, in juvenile sheep, similar samples were implanted into the jugular vein (blood contact) and into the carotid artery (blood contact and arterial stress). After 8 and 12 weeks, tissue was explanted and evaluated by X-ray, light- and electron-microscopy, and calcium content measurement (atomic absorption spectrometry). On the Von Kossa staining, auto-fluorescence of elastic fibers was used to identify the relation between calcific deposits and elastin. Subcutaneously implanted, glutaraldehyde-fixed tissue calcified severely in rat, but much less in sheep (calcium content: 56.2 +/- 13.6 v 9.9 +/- 9.0 microg/mg, respectively; P <.001). In sheep, the presence of blood contact (venous implants) increased wall calcification significantly (36.9 +/- 15.8; P <.001), but hemodynamic stress (arterial implants) had no additional mineralizing effect on the aortic wall (P >.05 v venous implants). Calcification of glutaraldehyde-fixed tissue occurred predominantly at the level of cells and cellular remnants, as confirmed by electron- and fluorescence-microscopy, locating calcific deposits in between elastic fibers. Acellularized tissue calcified significantly less, but an inflammatory response towards the tissue led to fragmentation, lysis, and subsequent calcification of elastic fibers. Results from subcutaneous implantations show large inconsistencies in calcification between the species. In sheep, blood contact increases aortic wall calcification significantly, while arterial stress has no additional effect. The sheep-jugular implantation model can be used as a simplified model for further study of aortic wall calcification and new antimineralization treatments. Calcification of glutaraldehyde-fixed aortic wall tissue is initiated at the level of cellular remnants, with little or no contribution from elastic fibers. Acellularization can avoid this cell-mediated calcification, but an additional treatment (glutaraldehyde, cryopreservation, photo-fixation,.) will be necessary to avoid the inflammation leading to elastolysis and consequent calcification of elastic fibers.
Seminars in thoracic and cardiovascular surgery, 2001
Valve dysfunction in right side implanted bioprostheses can be caused by fibrous sheathing and cu... more Valve dysfunction in right side implanted bioprostheses can be caused by fibrous sheathing and cusp retraction. A scoring system was employed to grade the macroscopic appearance of the cusp retraction. Stentless porcine aortic valves exhibit less cusp retraction when implanted in right-sided position than stented porcine aortic valves.
The study aim was to address independently, in a randomized patient cohort, the impact of Silzone... more The study aim was to address independently, in a randomized patient cohort, the impact of Silzone coating on the prevalence and impact of paravalvular leak in patients undergoing mechanical valve replacement. Randomized implantation of the uncoated St. Jude Medical Masters, and the Silzone-coated prosthesis was performed in 95 patients, excluding those with suspected or diagnosed infective endocarditis. The company did not support the study; this cohort is not contained in the AVERT trial. Following recall of the Silzone-coated valves, all patients in this cohort were invited to undergo control transthoracic echocardiography and plasma LDH determination. Silzone-coated valves were implanted in 46 patients (57 valves; 34 aortic, 20 mitral, three tricuspid), and uncoated valves in 49 patients (55 valves; 38 aortic, 16 mitral, one tricuspid). One patient with an uncoated mitral valve died from left ventricular dissection. In total, 73 patients returned for specifically planned echocardiography (mean interval 478+/-78 days). Sixteen patients underwent echocardiography on another occasion (mean interval 113+/-202 days). Six hospital survivors did not undergo any postoperative echocardiography. In total, 51 Silzone-coated valves (31 aortic, 18 mitral, two tricuspid), and 53 uncoated valves (37 aortic, 15 mitral, one tricuspid) were evaluated. No patients were reoperated for intrinsic or extrinsic valve dysfunction. No major paravalvular leaks were seen. Five of 51 Silzone-coated valves showed minimal (grade <1+; four aortic, one mitral) paravalvular leak when specifically sought; two showed minimal (grade <1+; one aortic, one mitral), and one slight (grade 1+; one mitral) paravalvular leak in the uncoated group (p = 0.55). The LDH level was 654+/-163 U/I in the Silzone group, and 598+/-124 U/l in the control group (p = 0.10). No differences were detected in the incidence of paravalvular leak between Silzone-coated and uncoated mechanical St. Jude Medical valves. The incidence of major paravalvular leaks appears to be lower in the present cohort than was reported in the AVERT trial.
Photo-oxidation treatment of porcine stentless bioprostheses (Photofix) was compared with glutara... more Photo-oxidation treatment of porcine stentless bioprostheses (Photofix) was compared with glutaraldehyde fixation, with either AOA (Freestyle valve) or Tween-80 (Edwards Prima Plus valve). Six valves of each type were implanted in juvenile sheep, in the pulmonary position. Valves were explanted after three or six months and examined macroscopically, by X-radiography, and by light and transmission electron microscopy. Calcium content was determined by atomic absorption spectrometry. The cusps of all valves were free of calcification, and had normal histology and function. Calcium contents (median +/- IQR) were 0.63+/-0.45, 0.73+/-1.46 and 0.46+/-1.42 microg/mg for the Photofix, Freestyle and Prima Plus valves, respectively (p = NS). Calcium contents of the aortic wall portions were 0.71+/-1.27 (Photofix), 10.78+/-77.22 (Freestyle) and 28.70+/-66.53 (Prima Plus) (p <0.05 for Photofix versus Freestyle or Prima Plus). Photo-oxidation of a porcine stentless valve prevents calcification not only in the cusps, but also in the aortic wall portion.
Seminars in thoracic and cardiovascular surgery, 1999
Allograft valved conduits are used routinely for reconstruction of the right ventricular outflow ... more Allograft valved conduits are used routinely for reconstruction of the right ventricular outflow tract in children with congenital heart disease; however, allografts are scarce. The purpose of this study was to evaluate two stentless aortic valves that might be suitable alternatives for right ventricular outflow tract reconstruction. Twelve juvenile sheep underwent implantation of stentless aortic heterografts as an interposition in the pulmonary artery: six porcine aortic valves (Freestyle) and six fully pericardial valves (Pericarbon stentless). In each series, three valves were explanted after 3 months, the other three after 6 months. Valves were analyzed by gross inspection, radiography, and light microscopy. The porcine aortic stentless valve (Freestyle) showed extensive calcification of its aortic wall portion, with perfectly functioning, pliable cusps without calcification or fibrous overgrowth up to 6 months. The pericardial valves (Pericarbon stentless) showed extensive fib...
Journal of Thoracic and Cardiovascular Surgery, 1996
This experimental study was designed to assess the influence of failure of the right side of the ... more This experimental study was designed to assess the influence of failure of the right side of the heart or pulmonary hypertension, or both, on the performance of a novel miniaturized left ventricular assist device. In small-sized dogs (n = 50) ischemic global left ventricular failure was induced and support was provided by the HIA-VAD displacement pump (stroke volume 10 or 25 ml) installed as a left ventricular assist device. In three groups of animals (n = 10 each) pulmonary hypertension was created before induction of global left ventricular failure. During left ventricular assist device support temporary ischemic failure of the right side of the heart was induced in four groups of animals (n = 10 each). In the group subjected to left ventricular failure, support with the left ventricular assist device, and right ventricular failure during left ventricular assist, left atrial pressure and cardiac index were significantly lower than in the group subjected to left ventricular failure and left ventricular assist alone (2 +/- 6 versus 11 +/- 6 mm Hg and 1.6 +/- 0.4 versus 1.0 +/- 0.4 L/(min/m2), respectively, p < 0.05). In the group subjected to pulmonary hypertension, left ventricular failure, and left ventricular support, left atrial pressure dropped to values near zero but cardiac index remained unaltered as compared with results with the same regimen without pulmonary hypertension. However, when right ventricular failure was added (that is, pulmonary hypertension, left ventricular failure, left ventricular support, and right ventricular failure during support with the left ventricular assist device) left atrial pressure dropped to negative values (p < 0.05) and cardiac index progressively deteriorated. When, in an additional group of dogs, biventricular support was installed in the latter regimen, circulation was initially well supported but oxygenation deteriorated in 60% of cases. We conclude that (1) adequate right ventricular function was indispensable during support with the left ventricular assist device, (2) the combination of pulmonary hypertension and right ventricular failure led to the "low left ventricular assist device output syndrome," and (3) biventricular mechanical support in the presence of pulmonary hypertension may be complicated by the alveolar leakage syndrome.
Objectives: Free fatty acid (FFA) oxidation is depressed in the postischaemic stunned myocardium ... more Objectives: Free fatty acid (FFA) oxidation is depressed in the postischaemic stunned myocardium and recovers in pitmllel with the normalization 01 contracti Ie performance. Assuming a causal role for this metabolic disturbance in the ptitbogencsis of' stunning, wc questioned whether exogenous administration of' high dose triglycerides during repertirsion of postischaemic myocardium. could impm~e its functional recovery. Methods: Thirteen dogs were
Cardiovascular diabetology, 2012
The number of patients with diabetes or the metabolic syndrome reaches epidemic proportions. On t... more The number of patients with diabetes or the metabolic syndrome reaches epidemic proportions. On top of their diabetic cardiomyopathy, these patients experience frequent and severe cardiac ischemia-reperfusion (IR) insults, which further aggravate their degree of heart failure. Food restriction and angiotensin-converting enzyme inhibition (ACE-I) are standard therapies in these patients but the effects on cardiac IR injury have never been investigated. In this study, we tested the hypothesis that 1° food restriction and 2° ACE-I reduce infarct size and preserve cardiac contractility after IR injury in mouse models of diabetes and the metabolic syndrome. C57Bl6/J wild type (WT) mice, leptin deficient ob/ob (model for type II diabetes) and double knock-out (LDLR-/-;ob/ob, further called DKO) mice with combined leptin and LDL-receptor deficiency (model for metabolic syndrome) were used. The effects of 12 weeks food restriction or ACE-I on infarct size and load-independent left ventricul...
Repair of complex valve pathological processes often requires the use of leaflet tissue or perica... more Repair of complex valve pathological processes often requires the use of leaflet tissue or pericardium. The use of bovine photo-oxidized pericardium may be an alternative, a tissue less prone to calcification. The aim of this study is to evaluate the use of photo-oxidized bovine pericardial tissue in the reconstruction of atrioventricular valves in humans. Between July 2001 and September 2006,
Background—Hypercholesterolemia induces functional and structural changes of the microvasculature... more Background—Hypercholesterolemia induces functional and structural changes of the microvasculature and reduces coronary flow reserve in humans and experimental animals. The effect of hypercholesterolemia on left ventricular (LV) function in the absence of coronary stenosis is, however, unknown. Our objective was therefore to assess the effect of hypercholesterolemia and cholesterol withdrawal on LV function in the presence of advanced coronary plaques
The Japanese Journal of Thoracic and Cardiovascular Surgery, 2002
Ischemic preconditioning (PC) has been proposed as an endogenous form of protection against-ische... more Ischemic preconditioning (PC) has been proposed as an endogenous form of protection against-ischemia reperfusion injury. We have shown that PC does not prevent post-ischemic dysfunction in the aging heart. This phenomenon could be due to the reduction of cardiac norepinephrine release and it has also been previously demonstrated that age-related decrease of norepinephrine release from cardiac adrenergic nerves may be restored by caloric restriction.
Perfusion, 2002
Today, rotary pumps are routinely used for extracorporeal circulation in different clinical setti... more Today, rotary pumps are routinely used for extracorporeal circulation in different clinical settings and applications. A review of these applications and specific limitations in extracorporeal perfusion was performed and served as a basis for the development of the DeltaStream. The DeltaStreams is a miniaturized rotary blood pump of a new and unique design with an integrated drive unit. Despite its small design, the pump maintains a sufficient hydraulic capacity, which makes the DeltaStream very flexible for intra- and perioperative applications. It also opens the field for short-term ventricular assist devices (VAD) applications or use as a component in extracorporeal life support systems (ECLS). The DeltaStream and, specifically, its impeller design have been optimized with respect to haemolysis and nonthrombogenicity. Also, the pump facilitates an effective pulse generation in VAD applications and simulates heart action in a more physiological way than other rotary pumps or rolle...
The Journal of thoracic and cardiovascular surgery, 2015
Despite improved anticalcification technology, bioprosthetic heart valves still cannot be used in... more Despite improved anticalcification technology, bioprosthetic heart valves still cannot be used in younger patients because of progressive structural valve degeneration. A novel advanced tissue preservation technology was developed that uses stable functional group capping and preservation by glycerolization. Valves incorporating this novel technology can be stored in a dry condition and do not require rinsing before use. The aim of the study was to assess the effects of this new technology in terms of valve function and durability in a chronic sheep model of orthotopic implantation. Forty-five juvenile sheep were randomized and either a Perimount mitral valve (6900P, control group) or the same valve design incorporating the novel tissue preservation technology (test group) was implanted in the mitral position. All valves were 25 mm. A transthoracic echocardiography was performed at 1 week and at 8 months postoperatively. The animals were then killed, an autopsy was performed, and th...
The Journal of heart valve disease, 2010
Triple valve surgery remains a challenge, although with an improved survival rate compared to his... more Triple valve surgery remains a challenge, although with an improved survival rate compared to historical data. Aws assessment was made as to whether the type of valve surgery, underlying valve lesion and pathology were independent predictors of outcome. The patient characteristics were also described according to the type of surgery performed. A total of 166 consecutive patients underwent triple valve surgery and were followed up between October 1972 and June 2006. The clinical and operative variables were obtained retrospectively by physicians. The median follow up was 6.11 years (interquartile range 2.13-10.43). The overall 30-day mortality was 10%, five-year survival 70%, and 10-year survival 60%. In patients with three mechanical valves, survival at five years was 90%, and 85% at 10 years, compared to 40% at five years and 30% at 10 years in patients with three bioprostheses. Among all patients with a mechanical valve in the aortic and mitral positions, those with a tricuspid bi...
Verhandelingen - Koninklijke Academie voor Geneeskunde van België, 2008
Preconditioning is the most powerful endogenous mechanism, to protect the heart against ischemic ... more Preconditioning is the most powerful endogenous mechanism, to protect the heart against ischemic damage. Conflicting data are published whether preconditioning can be induced in case of diabetes and the metabolic syndrome, which are clinically very relevant conditions. If preconditioning could be induced consistently and chronically in this population, an important reduction of surgical morbidity and mortality could be reached. In this project we induced hypoxic preconditioning in mice and used cardiac pressure-conductance catheterisation and infarct size as outcome parameters. In the first part, we found that hypoxic preconditioning was capable to reduce infarct size with 40% and preserve the load-independent parameters with 33% after coronary occlusion. A DKO (double knock-out: ob/ob; LDLR-/-) model for the metabolic syndrome developed a larger infarct size and had a reduced contractility. No preconditioning could be induced in this model. To detect the determing factor of the res...
Physiological research / Academia Scientiarum Bohemoslovaca, 2008
Reactive oxygen species (ROS) have been implicated in the mechanism of postischemic contractile d... more Reactive oxygen species (ROS) have been implicated in the mechanism of postischemic contractile dysfunction, known as myocardial stunning. In this study, we examined protective effects of antioxidant enzymes, superoxide dismutase (SOD) and catalase, against ischemia/reperfusion-induced cardiac dysfunction and inhibition of Na+,K+-ATPase activity. Isolated Langendorff-perfused rabbit hearts were subjected to 15 min of global normothermic ischemia followed by 10 min reperfusion. The hearts treated with SOD plus catalase did not show significant recovery of left ventricular (LV) end-diastolic pressure compared with untreated ischemic reperfused hearts. Treatment with antioxidants had no protective effects on developed LV pressure or its maximal positive and negative first derivatives (+/-LVdP/dt). Myocardial stunning was accompanied by significant loss in sarcolemmal Na+,K+-ATPase activity and thiol group content. Inhibition of enzyme activity and oxidation of SH groups were not preven...
Tissue degeneration and calcification are the two chief obstacles to the successful application o... more Tissue degeneration and calcification are the two chief obstacles to the successful application of bioprosthetic heart valves. To enable the study of the durability of bioprosthetic heart valves and the efficacy of anti-calcification treatment, it has become necessary to develop animal models. The aim of this study is to validate a new model for implantation in the pulmonary position. Three juvenile sheep underwent implantation of Carpentier-Edwards pericardial valves in the pulmonary position (experimental group). These three valves were compared with three Carpentier-Edwards pericardial valves in the aortic position in patients which had been explanted due to primary tissue failure (clinical group). The valves were analyzed. The findings of macroscopic, X-ray and light microscopic examination were very similar between the two groups. Scattered irregular calcification was seen near the commissures and at the base of the cusps in both groups. Quantitative calcium content analysis showed that calcification of the cusps had progressed to almost the same degree in both groups (experimental group, 3.7+/-0.2 micro g/mg dry tissue; clinical group, 4.3+/-0.3; p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;0.05). In the experimental group, calcification in the commissural area of the cusp was pronounced (6.5+/-1.0). In the clinical group, calcification had also progressed in the commissural area of the cusp (6.0+/-1.5), and extended to the base area of the cusp (6.6+/-1.2). This model is promising for preclinical evaluation of bioprosthetic heart valves. The degree of calcification is not significantly different between our experimental results after three months of implantation in sheep and clinical results after 10 years of implantation in elderly patients. However, the pattern of calcification is somewhat different between the two groups.
The Japanese journal of thoracic and cardiovascular surgery : official publication of the Japanese Association for Thoracic Surgery = Nihon Kyōbu Geka Gakkai zasshi, 2003
Stent mounting of any bioprosthesis, induces a loss of mobility and reduces the effective valve o... more Stent mounting of any bioprosthesis, induces a loss of mobility and reduces the effective valve orifice. By contrast, for stentless procedures, the higher surgical technicality remains a major obstacle for many surgeons. In an attempt to facilitate the insertion of the stentless porcine aortic valve (Toronto SPV), we tried to alter the design by lowering the invasive profile at the depth of the sinuses on both coronary sites. This could theoretically facilitate the implant of the modified stentless valve with an easygoing single layer suture at the challenging subcoronary level and make it more attractive for every surgeon. Modifications of the standard model were done by lowering the profile at the depth of the sinuses on both coronary sites, whether by plication or excision of the protruding porcine aortic wall at the nadir of each coronary sinus. Nine juvenile sheep underwent implantation of stentless porcine aortic valves in pulmonary position: 3 standard Toronto SPV, 3 plicated...
The rat subcutaneous model reproduces clinically observed mineralization of bioprosthetic tissues... more The rat subcutaneous model reproduces clinically observed mineralization of bioprosthetic tissues. However, the effectiveness of antimineralization treatment can be overestimated in subcutaneous implants, since specimens using this model are not subjected to mechanical and dynamic stress or blood-surface contact. The purpose of this study was to evaluate the influence of blood contact on the calcification of bioprosthetic valves. Glutaraldehyde-pretreated porcine aortic valves were prepared. Aortic wall and cusp discs were implanted subcutaneously in six rats for 8 weeks and were implanted within the jugular vein wall in six sheep for 3 and 6 months (blood contact model). Tissue discs were analyzed by gross inspection, radiography and light microscopy. Calcium content was determined by atomic absorption spectrometry. X-ray and light microscopic examination showed calcification in the cusps to be higher than that in the aortic wall in the rat subcutaneous model. On the other hand, in the blood contact model, the cusps were slightly calcified and calcification in the aortic wall was more pronounced. Calcium analysis in rats revealed more calcium in the cusp than in the aortic wall (71.5+/-9.7 g/mg dry tissue vs. 53.7+/-2.6, p=0.09). Tests for calcium content of the jugular vein samples in sheep showed significantly more calcium in the aortic wall than in the cusp (3 months, 7.9+/-1.5 vs. 0.3+/-0.1, p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.0001; 6 months, 77.2+/-6.1 vs. 27.2+/-10.2, p=0.0002). In addition, aortic wall and cusp calcification significantly increased with time. These data suggest that the results from the rat subcutaneous model were completely opposite to those for the blood contact model. This study confirms the need to include blood contact as a factor in in vivo pre-clinical valve testing.
Several animal models are currently used to study bioprosthetic tissue calcification. The study a... more Several animal models are currently used to study bioprosthetic tissue calcification. The study aim was to evaluate the influence of species and environmental factors (blood contact and arterial pressure) on valve tissue mineralization. Glutaraldehyde-fixed porcine cusps and aortic wall samples were implanted subcutaneously in rats (n = 6) and sheep (n = 18). In sheep, similar samples were also implanted into the jugular vein (blood contact) and carotid artery (blood contact and arterial pressure). Tissue was explanted at intervals up to three months and evaluated macroscopically, and by X-radiography, light and electron microscopy and calcium content measurement. After eight weeks in the subcutaneous position, glutaraldehyde-fixed cusps were severely calcified in rats, but not in sheep (78.6 +/- 28.3 and 0.3 +/- 0.5 microg Ca/mg, respectively; p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001). Aortic wall samples were calcified in both species, but less in sheep (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001). In sheep, blood contact without arterial pressure (venous implants) significantly increased the calcification of cusp and even more of aortic wall tissue. Arterial pressure had no effect on calcification of aortic wall tissue. Major inter-species inconsistencies were found in valve tissue calcification after subcutaneous implantation. In sheep, blood contact increased tissue calcification significantly, mainly in aortic wall samples. Arterial pressure did not enhance mineralization of aortic wall tissue.
Valve tissue calcification has complex host, implant, and mechanical determinants. We studied the... more Valve tissue calcification has complex host, implant, and mechanical determinants. We studied the influence of species (rat v sheep), environmental factors (presence v absence of blood contact and arterial stress), and tissue cellularity (normal v acellularized tissue) on porcine aortic wall mineralization. Porcine aortic wall samples underwent standard glutaraldehyde-fixation or combined enzyme-detergent acellularization. Samples were implanted subcutaneously in rats (n = 8) and in juvenile sheep (n = 8). Furthermore, in juvenile sheep, similar samples were implanted into the jugular vein (blood contact) and into the carotid artery (blood contact and arterial stress). After 8 and 12 weeks, tissue was explanted and evaluated by X-ray, light- and electron-microscopy, and calcium content measurement (atomic absorption spectrometry). On the Von Kossa staining, auto-fluorescence of elastic fibers was used to identify the relation between calcific deposits and elastin. Subcutaneously implanted, glutaraldehyde-fixed tissue calcified severely in rat, but much less in sheep (calcium content: 56.2 +/- 13.6 v 9.9 +/- 9.0 microg/mg, respectively; P <.001). In sheep, the presence of blood contact (venous implants) increased wall calcification significantly (36.9 +/- 15.8; P <.001), but hemodynamic stress (arterial implants) had no additional mineralizing effect on the aortic wall (P >.05 v venous implants). Calcification of glutaraldehyde-fixed tissue occurred predominantly at the level of cells and cellular remnants, as confirmed by electron- and fluorescence-microscopy, locating calcific deposits in between elastic fibers. Acellularized tissue calcified significantly less, but an inflammatory response towards the tissue led to fragmentation, lysis, and subsequent calcification of elastic fibers. Results from subcutaneous implantations show large inconsistencies in calcification between the species. In sheep, blood contact increases aortic wall calcification significantly, while arterial stress has no additional effect. The sheep-jugular implantation model can be used as a simplified model for further study of aortic wall calcification and new antimineralization treatments. Calcification of glutaraldehyde-fixed aortic wall tissue is initiated at the level of cellular remnants, with little or no contribution from elastic fibers. Acellularization can avoid this cell-mediated calcification, but an additional treatment (glutaraldehyde, cryopreservation, photo-fixation,.) will be necessary to avoid the inflammation leading to elastolysis and consequent calcification of elastic fibers.
Seminars in thoracic and cardiovascular surgery, 2001
Valve dysfunction in right side implanted bioprostheses can be caused by fibrous sheathing and cu... more Valve dysfunction in right side implanted bioprostheses can be caused by fibrous sheathing and cusp retraction. A scoring system was employed to grade the macroscopic appearance of the cusp retraction. Stentless porcine aortic valves exhibit less cusp retraction when implanted in right-sided position than stented porcine aortic valves.
The study aim was to address independently, in a randomized patient cohort, the impact of Silzone... more The study aim was to address independently, in a randomized patient cohort, the impact of Silzone coating on the prevalence and impact of paravalvular leak in patients undergoing mechanical valve replacement. Randomized implantation of the uncoated St. Jude Medical Masters, and the Silzone-coated prosthesis was performed in 95 patients, excluding those with suspected or diagnosed infective endocarditis. The company did not support the study; this cohort is not contained in the AVERT trial. Following recall of the Silzone-coated valves, all patients in this cohort were invited to undergo control transthoracic echocardiography and plasma LDH determination. Silzone-coated valves were implanted in 46 patients (57 valves; 34 aortic, 20 mitral, three tricuspid), and uncoated valves in 49 patients (55 valves; 38 aortic, 16 mitral, one tricuspid). One patient with an uncoated mitral valve died from left ventricular dissection. In total, 73 patients returned for specifically planned echocardiography (mean interval 478+/-78 days). Sixteen patients underwent echocardiography on another occasion (mean interval 113+/-202 days). Six hospital survivors did not undergo any postoperative echocardiography. In total, 51 Silzone-coated valves (31 aortic, 18 mitral, two tricuspid), and 53 uncoated valves (37 aortic, 15 mitral, one tricuspid) were evaluated. No patients were reoperated for intrinsic or extrinsic valve dysfunction. No major paravalvular leaks were seen. Five of 51 Silzone-coated valves showed minimal (grade <1+; four aortic, one mitral) paravalvular leak when specifically sought; two showed minimal (grade <1+; one aortic, one mitral), and one slight (grade 1+; one mitral) paravalvular leak in the uncoated group (p = 0.55). The LDH level was 654+/-163 U/I in the Silzone group, and 598+/-124 U/l in the control group (p = 0.10). No differences were detected in the incidence of paravalvular leak between Silzone-coated and uncoated mechanical St. Jude Medical valves. The incidence of major paravalvular leaks appears to be lower in the present cohort than was reported in the AVERT trial.
Photo-oxidation treatment of porcine stentless bioprostheses (Photofix) was compared with glutara... more Photo-oxidation treatment of porcine stentless bioprostheses (Photofix) was compared with glutaraldehyde fixation, with either AOA (Freestyle valve) or Tween-80 (Edwards Prima Plus valve). Six valves of each type were implanted in juvenile sheep, in the pulmonary position. Valves were explanted after three or six months and examined macroscopically, by X-radiography, and by light and transmission electron microscopy. Calcium content was determined by atomic absorption spectrometry. The cusps of all valves were free of calcification, and had normal histology and function. Calcium contents (median +/- IQR) were 0.63+/-0.45, 0.73+/-1.46 and 0.46+/-1.42 microg/mg for the Photofix, Freestyle and Prima Plus valves, respectively (p = NS). Calcium contents of the aortic wall portions were 0.71+/-1.27 (Photofix), 10.78+/-77.22 (Freestyle) and 28.70+/-66.53 (Prima Plus) (p <0.05 for Photofix versus Freestyle or Prima Plus). Photo-oxidation of a porcine stentless valve prevents calcification not only in the cusps, but also in the aortic wall portion.
Seminars in thoracic and cardiovascular surgery, 1999
Allograft valved conduits are used routinely for reconstruction of the right ventricular outflow ... more Allograft valved conduits are used routinely for reconstruction of the right ventricular outflow tract in children with congenital heart disease; however, allografts are scarce. The purpose of this study was to evaluate two stentless aortic valves that might be suitable alternatives for right ventricular outflow tract reconstruction. Twelve juvenile sheep underwent implantation of stentless aortic heterografts as an interposition in the pulmonary artery: six porcine aortic valves (Freestyle) and six fully pericardial valves (Pericarbon stentless). In each series, three valves were explanted after 3 months, the other three after 6 months. Valves were analyzed by gross inspection, radiography, and light microscopy. The porcine aortic stentless valve (Freestyle) showed extensive calcification of its aortic wall portion, with perfectly functioning, pliable cusps without calcification or fibrous overgrowth up to 6 months. The pericardial valves (Pericarbon stentless) showed extensive fib...