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Willem Flameng

Publications and source records attributed to Willem Flameng.

At least 19 recordsLinked to original sources

Type II diabetic mice exhibit contractile dysfunction but maintain cardiac output by favourable loading conditions.

BACKGROUND: Cardiomyopathy in type II diabetes is incompletely understood. The leptin receptor-deficient (db/db) mouse is a well-accepted model of type II diabetes. To date, left ventricular contractility has not been studied in animal models of type II diabetes with in vivo load-independent parameters. AIM: To determine cardiac function in db/db mice in vivo. METHODS: Cardiac function in 12- and 24-week-old db/db and wild-type mice was assessed using a microtip-pressure-conductance catheter. RESULTS: Left ventricular contractile dysfunction, measured by load-independent parameters (preload recruitable stroke work, end-systolic elastance, dP/dt-V(ed)), is present in diabetic mice from age 24 weeks onwards. Despite this contractile dysfunction, the conventional parameters cardiac output, ejection fraction and dP/dt(max) were maintained, which was due to an increased preload and decreased afterload. Ventriculo-arterial coupling was increased and mechanical efficiency significantly reduced in db/db mice. CONCLUSION: Our results demonstrate that, despite impaired cardiac contractility and mechanical efficiency, cardiac output is maintained in db/db mice by favourable loading conditions and that in vivo load-independent measurements are necessary to fully characterize cardiac performance in animal models of pathophysiological states.

Animals↗

Prosthesis-patient mismatch is not clinically relevant in aortic valve replacement using the Carpentier-Edwards Perimount valve.

BACKGROUND: Previous studies have shown that prosthesis-patient mismatch (PPM) results in higher early and late mortality after bioprosthetic aortic valve replacement. Careful selection of stented bioprostheses was recommended to avoid inadequate effective orifice area. We studied the incidence of PPM and its potential effects on clinical outcome in patients undergoing aortic valve replacement using the Carpentier-Edwards Perimount bioprosthesis. METHODS: Independent predictors of early and late mortality and hospital readmission for cardiac reasons were defined in 506 patients (mean age, 73 years; range, 57 to 87 years) by multivariate analysis. Mean follow-up was 6.1 +/- 4.8 years; maximum follow-up was 18.6 years. RESULTS: The incidence of severe PPM (effective orifice area index < 0.65 cm2/m2) was 0.2% and of moderate PPM (effective orifice area index > 0.65 and < 0.85) was 20%. Multivariate analysis revealed that moderate PPM was not an independent predictor of early mortality, late mortality, or hospital readmission for cardiac reasons. Reduction of septal hypertrophy was similar in patients with and without moderate PPM. CONCLUSIONS: The incidence of severe PPM is virtually nonexistent after aortic valve replacement using the Carpentier-Edwards Perimount valve. Moderate PPM is found in 20% of cases and is clinically irrelevant in this population.

Aged↗

Factors influencing calcification of cardiac bioprostheses in adolescent sheep.

OBJECTIVE: We determined the possible effects of age, antimineralization treatments, circulatory implant conditions, prosthesis design, and valve-related structural aspects on valve calcification in adolescent sheep. METHODS: Calcium content was measured by means of atomic absorption spectrometry in bioprostheses implanted in 120 sheep (age <1 year) for a period of 3 or 6 months. RESULTS: Bioprostheses calcified significantly in adolescent sheep, but the extent of calcification was multifactorial. Multivariate analysis of the calcium content reveals that age, mitral or pulmonary implant position, prosthesis design (stented or stentless), structure (porcine or pericardial, wall portion or cusp), and antimineralization treatment are independent factors influencing calcification; implant duration beyond 3 months was not. In juvenile sheep (age 5 months) the wall portion, as well as the cusps of the prosthesis, calcified significantly more than in adolescent sheep (age 11 months). Irrespective of age, the cusps of valves implanted in the mitral position calcified more than those in the pulmonary position. The wall portion of stentless valves calcified more than that of stented valves, and pericardial valves calcified less than porcine valves. The surfactant (Tween 80, No-React, and alpha-amino-oleic acid) and alcohol (ethanol and octanediol) treatment significantly reduced cusp calcification; sodium dodecylsulfate did not. None of the anticalcification treatments was able to prevent wall calcification in stentless porcine valves. CONCLUSION: These findings suggest that tissue valve calcification is determined by many independent factors, which can be identified by using adolescent sheep as a preclinical in vivo model.

Age Factors↗

Simultaneous valve replacement and venous patch repair of superior mesenteric artery aneurysm due to infective endocarditis: a case report.

BACKGROUND: Peripheral mycotic aneurysm development is a rare systemic complication of infective endocarditis. CASE REPORT: We report on a case of a mycotic aneurysm of the superior mesenteric artery in a 66-year-old man with infective endocarditis of the mitral valve. After the mitral valve was replaced by a mechanical valve, a laparotomy was performed. The mycotic aneurysm was excised and the vessel was repaired by sewing an autologous venous patch at the neck of the aneurysm. Five years after the operation, the patient is doing fine, with a normal morphology and patency of the superior mesenteric artery. CONCLUSION: Our case demonstrates that simultaneous valve surgery and repair of a superior mesenteric artery mycotic aneurysm by sewing a vein patch in the neck of the artery is a viable treatment option.

Aged↗

Increased cardiac expression of tissue inhibitor of metalloproteinase-1 and tissue inhibitor of metalloproteinase-2 is related to cardiac fibrosis and dysfunction in the chronic pressure-overloaded human heart.

BACKGROUND: Alterations in the balance of matrix metalloproteinases (MMPs) and their specific tissue inhibitors (TIMPs) are involved in left ventricular (LV) remodeling. Whether their expression is related to interstitial fibrosis or LV dysfunction in patients with chronic pressure overload-induced LV hypertrophy, however, is unknown. METHODS AND RESULTS: Therefore, cardiac biopsies were taken in 36 patients with isolated aortic stenosis (AS) and in 29 control patients without LV hypertrophy. Microarray analysis revealed significantly increased mRNA expression of collagen types I, III, and IV and transcripts involved in collagen synthesis, including procollagen endopeptidase and lysine and proline hydroxylases, in AS compared with control patients. Collagen deposition was greater in AS than in control patients and was most pronounced in AS patients with severe diastolic dysfunction. Cardiac mRNA expression of TIMP-1 and TIMP-2 was significantly increased in AS compared with control patients (mRNA transcript levels normalized to GAPDH: TIMP-1, 0.67+/-0.1 in AS versus 0.37+/-0.08 in control patients; TIMP-2, 9.5+/-2.6 in AS versus 1.6+/-0.4 in control patients; P<0.05 for both) but did not differ significantly for MMP-1, -2, or -9. Cardiac TIMP-1 and -2 transcripts were significantly related to the degree of interstitial fibrosis and proportional to diastolic dysfunction in AS patients. CONCLUSIONS: Cardiac expression of TIMP-1 and TIMP-2 is significantly increased in chronic pressure-overloaded human hearts compared with controls and is related to the degree of interstitial fibrosis.

Aortic Valve Stenosis↗

Migration of two venous stents into the right ventricle in a patient with May-Thurner syndrome.

May-Thurner syndrome is an uncommon process in which the right common iliac artery compresses the left common iliac vein, possibly resulting in pain, severe edema of the left leg or in left iliofemoral deep vein thrombosis [May R, Thurner J. The cause of the predominately sinistral occurrence of thrombosis of the pelvic veins. Angiology 1957; 8: 419-427 .]. Corrective surgical treatment requires extensive dissection. Therefore, endovascular venous stenting is currently used in these patients [Lamont JP, Pearl GJ, Patetsios P, Warner MT, Gable DR, Garrett W, et al. Prospective evaluation of endoluminal venous stents in the treatment of the May-Thurner syndrome. Ann Vasc Surg. 2002 Jan; 16(1): 61-4. Epub 2002 Jan 17 .]. We present a case of migration of two iliacal vein stents into the right ventricle in a patient with May-Thurner syndrome.

Constriction, Pathologic↗

Effect of free radical scavengers on myocardial function and Na+, K+-ATPase activity in stunned rabbit myocardium.

OBJECTIVES: The role of reactive oxygen species (ROS) in the mechanism of myocardial stunning was investigated. MATERIAL AND METHODS: Isolated Langendorff-perfused rabbit hearts were subjected to 15 min normothermic ischemia followed by 10 min reperfusion with Krebs-Henseleit solution+/-mannitol or histidine. RESULTS: In hearts reperfused without free radical scavenger the left ventricular developed pressure as well as its maximal positive and negative first derivatives (+dP/dt, -dP/dt) was significantly depressed, whereas end diastolic pressure (LVEDP) increased when compared to preischemic values. Treatment with mannitol had little protective effects, whereas singlet oxygen scavenger histidine significantly improved the recovery of LVEDP and -dP/dt. Sarcolemmal Na+, K+-ATPase activity (control, 400+/-41 nmol Pi.min-1.mg-1) was depressed in untreated stunned hearts (260+/-27 nmol Pi.min-1.mg-1), but was almost completely recovered in hearts pretreated with histidine (364+/-27 nmol Pi.min-1.mg-1). The inhibition of Na+, K+-ATPase was only slightly prevented by mannitol (302+/-29 nmol Pi.min-1.mg-1l). CONCLUSIONS: The results suggest that ROS-induced inhibition of Na+, K+-ATPase activity is involved in the mechanism of postischemic contractile dysfunction and support the view that singlet oxygen may be one of the major causes of oxidative injury during ischemia and reperfusion.

Animals↗

Pentobarbital fails to reduce cerebral oxygen consumption early after non-hemorrhagic closed head injury in rats.

It is unknown whether barbiturates suppress cerebral oxygen metabolism after cerebral trauma as they do in normal individuals. We evaluated the influence of pentobarbital on cerebral oxygen handling of normal rats and rats subjected to non-hemorrhagic closed head injury (CHI). Oxygen delivery was assessed by measuring cerebral perfusion and oxygen extraction, enabling the calculation of cerebral metabolic rate of oxygen (CMRO2). Mitochondrial function was assessed by studying changes in the oxidized cytochrome oxidase concentration. CHI caused changes in both systemic and cerebral hemodynamics. Cerebral blood flow was reduced to 66% of its control value, but the cerebral metabolic rate of oxygen remained unchanged. Pentobarbital administration induced a significant lowering of the cerebral oxygen consumption in normal rats associated with a secondary decrease in cerebral perfusion. In rats subjected to CHI, pentobarbital was unable to lower the cerebral metabolic demand and did not cause a further decrease in perfusion. Pentobarbital was unable to significantly modulate mitochondrial function in traumatized rats, whereas it exerted this effect in all control animals. We therefore conclude that, in rats subjected to CHI, pentobarbital is unable to perform its beneficial effects on the cerebral metabolism.

Animals↗

Mechanical valve thrombosis in a chronic animal model: differences between monoleaflet and bileaflet valves.

BACKGROUND AND AIM OF THE STUDY: The occurrence of mechanical valve thrombosis was studied in a chronic sheep model of valve implantation in the pulmonary position. METHODS: Six monoleaflet and six bileaflet mechanical valves were implanted in young sheep. Anticoagulation was stopped at one week postoperatively, after which weekly fluoroscopic evaluation was performed. Animals were sacrificed at the moment of any abnormality on the fluoroscopic image or, if no abnormality occurred, at fixed time intervals of two and three months. After explantation, valves were examined macroscopically, by stereomicroscopy, histology and scanning electron microscopy. Lung biopsies were taken. RESULTS: All monoleaflet valves remained functionally intact for up to three months without anticoagulation, but explantation after two or three months revealed thrombi attached to struts, cuspal surface and valve ring. All bileaflet valves, except one, showed obvious dysfunction on fluoroscopy (one or both cusps fixed) within a time frame of three to eight weeks after implantation. Histology and scanning electron microscopy showed primary thrombotic material in one or both hinges, obstructing further cusp movement. Lung embolism was detected in only one animal among biopsy specimens. CONCLUSION: The low-pressure environment of the pulmonary position caused primary thrombotic changes in all implanted mechanical valves. The thrombosis caused severe mechanical dysfunction only in the bileaflet valves, probably due to their delicate hinge mechanism. These findings may be used in the further development of an animal model of mechanical valve thrombosis.

Animals↗

Prevention of porcine aortic wall calcification by acellularization: necessity for a non-glutaraldehyde-based fixation treatment.

BACKGROUND AND AIM OF THE STUDY: Acellularization prevents cell-mediated calcification of the aortic wall, but the inflammatory response towards the unfixed tissue is problematic. Two additional fixation methods, applied after tissue acellularization, were studied. METHODS: Porcine aortic wall samples were randomized into four groups: (1) Standard fixation with glutaraldehyde (GA); (2) acellularization by a combined method of enzymes (DNase, RNase) and a detergent (Triton X-100); (3) acellularization followed by standard GA fixation; (4) acellularization followed by photo-oxidation. Samples were implanted into the wall of both jugular veins of six juvenile sheep. Tissue was explanted after three months and evaluated by X-radiography, light and electron microscopy, and calcium content (cc) measurement (atomic absorption spectrometry). Auto-fluorescence of elastic fibers was used to identify the relationship between calcific deposits and elastin. RESULTS: GA-fixed aortic wall samples showed clear mineralization (cc 41.6 +/- 17.8 microg/mg), occurring predominantly at the level of cell remnants, as confirmed by electron- and fluorescence microscopy, locating calcific deposits in between elastic fibers. Acellularized aortic wall fragments were calcified significantly less, but an important (non-infectious) inflammatory response caused elastolysis and subsequent calcification of the elastic fibers (cc 5.6 +/- 2.8 microg/mg). Acellularized and GA-fixed fragments revealed important, inhomogeneously spread calcific deposits (cc 24.7 +/- 10.0 pg/mg). Photo-oxidized samples remained free from calcification (cc 0.82 +/- 1.6 microg/mg). CONCLUSION: Acellularization is a promising tool in the prevention of porcine aortic wall calcification, but additional tissue fixation is necessary to prevent structural degeneration. GA fixation after acellularization causes important inhomogeneous tissue mineralization. Photo-oxidation combines optimal tissue fixation with superior anticalcification characteristics.

Animals↗

Reduced synchrony of Ca2+ release with loss of T-tubules-a comparison to Ca2+ release in human failing cardiomyocytes.

OBJECTIVES: During cardiac excitation-contraction coupling, Ca2+ release from the sarcoplasmic reticulum (SR) occurs at the junctional complex with the T-tubules, containing the L-type Ca2+ channels. A partial loss of T-tubules has been described in myocytes from failing canine and human hearts. We examined how graded reduction of T-tubule density would affect the synchrony of Ca2+ release. METHODS: Adult pig ventricular myocytes were isolated and cultured for 24 and 72 h. T-tubules, visualized with di-8-ANEPPS, and [Ca2+]i transients (Fluo-3) were recorded during confocal line scan imaging. RESULTS: Cultured cardiomyocytes exhibited a progressive reduction in T-tubule density. [Ca2+]i transients showed small areas of delayed Ca2+ release which gradually increased in number and size with loss of T-tubules. Local [Ca2+]i transients in the delayed regions were reduced. Due to these changes, loss of T-tubules resulted in an overall slowing of the rise of [Ca2+] along the entire line scan and transient magnitude tended to be reduced, but there was no change in SR Ca2+ content. Human myocytes isolated from failing hearts had a T-tubule density comparable to that of freshly isolated pig myocytes. The size, but not the number, of delayed release areas tended to be larger. The overall rate of rise of [Ca2+]i was significantly faster than in pig myocytes with low T-tubule density. CONCLUSIONS: Loss of T-tubules reduces the synchrony of SR Ca2+ release. This could contribute to reduced efficiency of excitation-contraction coupling in heart failure, though dyssynchrony in human failing cells appears to be modest.

Animals↗

Pericardial synovial sarcoma: 14-year survival with multimodality therapy.

We report a case of recurrent primary synovial sarcoma of the pericardium. Reverse transcriptase-polymerase chain reaction analysis for t(X,18) demonstrated the presence of the chimeric transcript SYT/SSX. Because of the rarity of this entity, optimal therapy is unknown. The prognosis of this tumor is very poor in previous reports. In this report, we present a case with five recurrences treated by a combination of surgery, chemotherapy, and radiotherapy. The patient survives now for more than 14 years, the longest reported survival of a primary synovial sarcoma of the pericardium.

Adult↗

Endothelial activation through brain death?

BACKGROUND: Brain death induces myocardial dysfunction and multifocal microscopic myocardial necrosis in dogs; however, the pathogenetic pathways between brain death and cardiac damage remain incompletely understood. We hypothesized that brain death might induce a propensity toward coronary vasospasms, possibly by endothelial dysfunction. We therefore studied the effect of serotonin and acetylcholine on tension generated by isolated coronary artery segments from control and brain dead dogs. METHODS: Coronary segments were isolated 1 hour after brain death that was induced by the inflation (15 ml saline) of an extradurally placed balloon or from sham-operated time-matched controls. Studied were the effect of serotonin on isometric tension, with and without pre-constriction with prostaglandin F(2alpha) (PGF(2alpha)), and the effect of acetylcholine after pre-constriction. RESULTS: Coronary segments from brain dead dogs exhibited severe vasoconstriction when serotonin (10(-7), 10(-6), and 10(-5) mol/liter) was administered, a reaction that was barely detectable in control segments. After pre-construction with PGF(2alpha), serotonin caused only significant vasodilation in a concentration of 10(-5) mol/liter, unlike in control segments where 10(-6) mol/liter had already induced a highly significant vasodilation. The reaction on acetylcholine was identical in both groups. CONCLUSION: Brain death induces changes in coronary vasoreactivity in dogs, with a highly increased sensitivity for the vasospastic effects of serotonin. It is, however, not merely caused by aspecific endothelial dysfunction, as evidenced by the normal reaction on acetylcholine. These alterations in coronary artery properties might contribute to the myocardial damage seen after brain death.

Acetylcholine↗